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the Quest to Cure Diabetes


									                                                                          VO LU M E 6 N U M B E R 3 | FA L L 2 0 0 9

                                                                  From Research,The Power to Cure

InsIde   > D iA B E t E s RE s EARc h   >B URNh AM N Ews   >Phi L ANth ROPy

                the Quest
to Cure Diabetes
BUrnham REPORt

iN this issUE                                                        Founders                                Trustees, continued
                                                                     wi LLiAM h . Fish MAN, Ph.D.            Alan Gleicher
BURNhAM REsEARch                                                     LiLLiAN Fish MAN                        W.D. Grant
                                                                     honorary trustees                       David Hale
The Quest to Cure Diabetes                                       1
                                                                                                             Jeanne Herberger, Ph.D.
                                                                     JOE LEwis
     Diabetes and its Consequences                               3                                           Brent Jacobs
                                                                     c ONRAD t. P REBys
                                                                                                             James E. Jardon II (Florida)
     A National Quest                                            5   t. D ENNy sANFORD
                                                                                                             Daniel P. Kelly, M.D.
                                                                     trustees and Officers                   Robert J. Lauer
BURNhAM NEws                                                         MALi N B URN hAM                        Sheila B. Lipinsky
                                                                     Chairman                                Gregory T. Lucier
The View from Lake Nona                                          7   JO h N c. R EED , M.D., Ph.D.           Papa Doug Manchester
                                                                     President & Chief Executive Officer     Robert A. Mandell (Florida)
Science News                                                     8
                                                                     Professor and Donald Bren               Nicolas C. Nierenberg
New Faculty                                                     11   Presidential Chair                      Douglas H. Obenshain
                                                                     G ARy F. R Ais L, E D.D.                Peter Preuss
Collaborations                                                  13   Chief Administrative Officer            John C. Reed, M.D., Ph.D.
                                                                     Treasurer                               Stuart Tanz
PhiL ANthROPy                                                        MARG ARE t M. D UNBAR                   Jan Tuttleman, Ph.D., MBA
                                                                     Secretary                               Andrew J. Viterbi, Ph.D.
Burnham Welcomes Julie Johnson                                  14                                           Kristiina Vuori, M.D., Ph.D.
                                                                     trustees                                Bobbi Warren
Lake Nona Events                                                15   Linden S. Blue                          Allen R. Weiss (Florida)
La Jolla Events                                                 16   Mary Bradley                            Judy White
                                                                     Brigitte Bren                           Gayle E. Wilson
                                                                     Arthur Brody                            Diane Winokur
AROUND BURNhAM                                                       Malin Burnham                           Kenneth J. Woolcott
                                                                     Howard I. Cohen
President’s Message                                             17                                           Ex-Officio
                                                                     Shehan Dissanayake, Ph.D.
Partners in Science                                             18   M. Wainwright Fishburn, Jr.             Raymond L. White, Ph.D.
                                                                     Jeannie M. Fontana, M.D., Ph.D.         Chairman, Science Advisory Committee

                                     ON thE cOVER
                                                                     B L Ai R B LUM                        JO sh BA xt
                                     Drs. Timothy Osborne,           Senior Vice President                 Editor, Burnham Report
                                     Stephen Gardell                 External Relations
                                                                                                           G AVi N & G AViN
                                     and Daniel Kelly are            ELiz ABEth Gi AN iNi                  ADVERtisi NG
                                     committed to finding            Vice President                        Design
                                                                     External Relations
                                     new ways to treat type                                                Mic h AEL cAiRNs
                                     2 diabetes and related          EDG AR Gi LLENwAt ERs                 MAR k DAst RUP
                                                                     Vice President                        NAD i A BOROwski sc Ott
                                     diseases. As director of        External Relations                    Photography
                                     the Metabolic Signaling
                                                                     c hR is L EE                          kEN G. c OVENE y, Esq.
                                     and Disease Program,            Vice President                        FAB iAN V. Fi L iPP, Ph.D.
                                     Dr. Osborne wants to            External Relations                    Contributors
illuminate the normal signaling mechanisms that control              ANDREA M Os ER                        Please address inquiries to:
metabolism and how those signals differ in diseased tissue.          Vice President              
Dr. Steve Gardell directs Translational Research Resources,          Communications
which seeks to move basic research findings from the labo-
                                                                     Burnham Institute for Medical Research
ratory to the clinic. Scientific Director Dr. Daniel Kelly
                                                                     10901 North Torrey Pines Road, La Jolla, CA 92037 • 858.646.3100
investigates cardiovascular disease and wants to expose its
                                                                     Burnham Institute for Medical Research at Lake Nona
different causes and discover new treatments.
                                                                     6400 Sanger Road, Orlando, FL 32827 • 407.745.2000
                                                                                           BUrnham DiABEtEs REsEARch

                                         the Quest
                          to Cure Diabetes

                                                                                 Pancreatic beta cells – photo by Ifat Geron, Levine and Itkin-Ansari laboratories

In 1922, insulin was first      reduces lifespan, on average,         Though treatments for                      autoimmune disorder, in which
administered to treat           by seven to 10 years.             both forms of diabetes have                    the body’s immune system
type 1 diabetes, trans-             Type 2 diabetes—a quite       advanced, cures remain                         attacks and destroys beta cells,
forming a deadly disease        different disease—is associ-      elusive. At Burnham, signifi-                  which monitor blood glucose
into a chronic one. But         ated with obesity and is fast     cant work is being done on                     and release insulin. In type 2
insulin is not a cure.          becoming an epidemic in the       both coasts to understand                      diabetes, high levels of fatty
                                United States. While type 1       these conditions and find new                  acids attack beta cells. As beta
                                results from a lack of insulin,   treatments.                                    cells die, glucose accumulates
Periodic blood sugar moni-      type 2 appears when cells                                                        in the blood, leading to deadly
toring and insulin injections   lose the ability to respond       MAkiNG N Ew iN sULi N-                         complications. However, if
cannot match the 24/7 effi-                                       PRODUciNG cELL s
                                to insulin (See box, page 3).                                                    we could transplant or renew
ciency of insulin-producing                                           Both type I and type II
                                According to the American                                                        beta cells, the body could once
beta cells. According to the                                      diabetes are caused by a
                                Diabetes Association, more                                                       again produce its own insulin.
Juvenile Diabetes Research                                        deficiency of the cells that
                                than 23 million people have                                                          Currently, beta cells are
Foundation, type 1 diabetes                                       produce insulin. Type 1 is an
                                diabetes, mostly type 2.                                                         transplanted from cadavers

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BUrnham DiABEtEs REsEARch

                                                                                                                                    biology, we may find thera-
                                                                                                                                    peutic targets where you add a
                                                                                                                                    drug or apply gene therapy to
                                                                                                                                    encourage the body to regen-
                                                                                                                                    erate the cells.”
                                                                                                                                        The Dong laboratory,
                                                                                                                                    which uses zebrafish as a
                                                                                                                                    research model, is also trying
                                                                                                                                    to encourage pancreatic
                                                                                                                                    exocrine cells, which produce
                                                                                                                                    digestive enzymes, to become
                                                                                                                                    beta cells.
                                                                                                                                        “They come from the same
                                                                                                                                    precursors,” says Dr. Dong.
                                                                                                                                    “We found that a particular
                                                                                                                                    gene helps decide the fate of
                                                                                                                                    these precursors. We hope
                                                                                                                                    that, by manipulating this
                                                                                                                                    gene, we can help make more
                                                                                                                                    beta cells.”
                                                                 Dr. Fred Levine chats with postdoctoral fellow Dr. Seung-Hee Lee       Taking a different
but quantities are very low.            we made turned out to be ideal           screening, Dr. Levine’s labora-                    approach, Alex Strongin,
Fred Levine, M.D., Ph.D.,               for high-throughput screening            tory is also pursuing other                        Ph.D., is interested in what
directs the Sanford Children’s          to search for drugs that affect          avenues. What if adult stem                        happens if the immune
Health Research Center                  beta cells. This project, done           cells, or mature endocrine                         system can be selectively
and is trying to solve the              in collaboration with Burnham            cells, could be transformed                        blocked. Dr. Strongin studies
problem of making new beta              investigators Drs. Mark                  into beta cells? Dr. Levine is                     an enzyme that helps inva-
cells—either outside the body           Mercola, Pamela Itkin-Ansari             collaborating with Burnham                         sive cancer cells migrate to
for transplantation or by acti-         and Jeff Price, as well as the           stem cell scientists, such as Dr.                  other parts of the body. The
vating adult stem cells within          Conrad Prebys Center for                 Alexey Terskikh, to understand                     enzyme, called MT1-MMP,
the pancreas.                           Chemical Genomics, has                   the genes that induce adult                        is a proteinase, a protein
    “Our initial intent was to          been a long road but has                 stem cells in the pancreas to                      that cuts up other proteins.
make a cell line that would             recently borne fruit, with               become functioning beta cells.                     MT1-MMP interacts with a
mimic beta cells so well they           a number of compounds                                                                       cell surface receptor called
could be transplanted,” says Dr.        entering preclinical trials.”            POssiBi Liti Es iN                                 CD44, which plays a number
                                                                                 REGENERAtiON                                       of roles in cancer cells and
Levine. “While that goal proved             In addition to the studies
                                                                                     Like Dr. Levine, Duc Dong,                     autoimmune T cells—the
overly ambitious, the cells that        with high-throughput
                                                                                 Ph.D., is trying to regenerate                     culprits in beta cell destruc-
                                                                                 beta cells from cells that                         tion. Dr. Strongin has found
     Dr. Levine is collaborating with                                            already exist in our bodies.                       that inhibiting MT1-MMP
Burnham stem cell scientists, such as Dr. Alexey                                     “Usually in diabetes there                     keeps T cells out of the
                                                                                 are a few beta cells left,”                        pancreas.
           Terskikh, to understand the genes
                                                                                 says Dr. Dong. “How can                                “We found that if you stop
  that induce adult stem cells in the pancreas to                                we replenish them? If we                           the killer cells from getting
         become functioning beta cells.                                          understand the developmental                       into the pancreas, it gives beta

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                                                                                          BUrnham DiABEtEs REsEARch

cells the opportunity to regen-     system must be controlled.
erate,” says Dr. Strongin.          Current transplant recipients
    The tricky part is finding      must take immunosuppres-
the right inhibitor. Dr. Strongin   sive drugs to prevent their T
notes that an MT1-MMP               cells from attacking replace-
inhibitor has failed in clinical    ment beta cells, presenting a
trials for late-stage cancer. To    stark choice between diabetes
be useful, the compound must        and a suppressed immune
be minimally toxic.                 system.
    “We would have to develop           Recently, Burnham
a less toxic inhibitor because      adjunct professor Pamela
patients would be taking it for     Itkin-Ansari, Ph.D., placed
the rest of their lives,” says      pancreatic precursor cells
Dr. Strongin. “It’s one thing       in an immunoprotective
to have a toxic treatment for       device and transplanted them
cancer and another entirely         into mice. She was testing
for diabetes, where insulin         whether precursor cells would
is an effective treatment. So,      mature into productive beta
there’s still a great deal of       cells in the body and whether
                                                                                                                         Dr. Duc Dong in the zebrafish facility
work to be done.”                   the protective device, made
                                    from a material akin to          the immune system rather               glucose and produced insulin
P ROt Ec t iNG c E L L s            Gore-Tex, could prevent          than suppressing the immune            and the immunoprotective
F RO M t hE i M M U N E                                              system,” says Dr. Itkin-Ansari.        device kept the immune
                                    the immune system from
systE M
                                    attacking transplanted cells.        Early studies have been            system at bay.
   For transplantation to be a
                                        “We wanted to see if we      very positive, as the trans-               “We are excited to see
viable treatment, the immune
                                    could protect the cells from     planted cells responded to             how well they did,” says Dr.

  Diabetes and its                                                   foreign and destroy them,
                                                                     reducing or eliminating
                                                                                                          cells, which ultimately fail
                                                                                                          and die.

                                                                     insulin production.                      High circulating glucose
                                                                         In type 2 diabetes, the          levels damage cells. Because
                                                                     problem is with the insulin          glucose moves primarily
                                                                     receptor—the lock that               through blood, the cells
       Insulin is produced in the    cells and telling them to let   allows glucose to enter. For         lining blood vessels are the
   pancreas by beta cells, which     glucose inside.                 reasons that are not clear,          most severely hurt. These
   measure glucose (the main             In type 1 diabetes, beta    the receptor mechanism               consequences extend to
   source of energy from food)       cells are destroyed by the      does not work properly,              virtually every organ in the
   in the blood and secrete          body’s own immune system.       even when insulin is                 body. Diabetes is a leading
   insulin to control glucose        White blood cells that          present. The body responds           cause of blindness, kidney
   concentrations. Insulin acts      ordinarily protect us from      by producing more insulin.           disease, amputation, heart
   as a key, binding to recep-       bacteria and viruses mistak-    While that works for a               disease and many other
   tors (locks) expressed by all     enly recognize beta cells as    time, it overworks the beta          conditions.

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BUrnham DiABEtEs REsEARch

                                                                               play a role in insulin resis-     fat is linked to higher blood
                                                                               tance and fatty liver disease,”   pressure and triglycerides
                                                                               says Dr. Wood.                    and makes that person a
                                                                                   Given that recent statis-     candidate for heart attack,
                                                                               tics show a third of Americans    diabetes, or both,” says Dr.
                                                                               are obese, the research being     Wood. “Visceral fat tissue
                                                                               done by Dr. Wood and others       leaks fatty acids, which go
                                                                               could have a profound impact      to the liver and cause fatty
                                                                               on the nation’s health. One       liver disease, enter the
                                                                               key focus is the underlying       blood as triglycerides and
                                                                               genetics that make certain        also cause inflammation.
                                                                               people susceptible to disease.    The most disturbing part is
                                                                                   “We’re not likely to find     that today’s children may be
                                                                               specific genes that cause         the first in history to have a
                                                                               type 2 diabetes,” says Dr.        shorter lifespan than their
                                                                               Wood. “Perhaps they exist in      parents because of obesity-
                                                                               rare cases, but not enough        related diseases.”
                                                                               for a genetic risk assess-            While Dr. Wood is
                                                                               ment. We’re not looking for       focused on what goes
                                                                               the cause of the disease;         wrong for people with type
                                                                               we’re looking at the genetic      2 diabetes, Tim Osborne,
                                                                               and environmental determi-        Ph.D., wants to understand
                                                             Dr. Philip Wood
                                                                               nants of the body’s response      the processes that make the
                                                                               to this burden of excess fat.     metabolism run normally.
Itkin-Ansari. “We could                mechanisms behind type 2                Why do some people have               “There’s a lot of synergy
see evidence of beta cells             diabetes, in which insulin              a predisposition towards          between Dr. Wood’s
forming and replicating. That          levels are normal (or elevated)
means the environment in               but cells do not respond to
the device was conducive               its signals. Scientists want to              The most disturbing part is that
to beta cells continuing               know why insulin resistance             today’s children may be the first in
to develop and survive.                happens in the first place,
                                                                                        history to have a shorter lifespan
Also, we thought that T                how diabetes affects the
cells, although unable to              heart and the role fat plays in                      than their parents because of
penetrate the device, would            diabetes, metabolic syndrome              obesity-related diseases.
cluster around it. But we              and other conditions.
found no evidence of an                     Philip A. Wood, D.V.M.,            insulin resistance in the face    research and mine,” says
active immune response,                Ph.D., is interested in fat: fat        of obesity? So we’re looking at   Dr. Osborne. “He comes
suggesting that the cells in           metabolism, fatty acids, fat            the genetics of response, not     at it from the disease side,
the device were invisible to           signaling, fatty liver disease.         the genetics of cause.”           and we’re interested in
the immune system.”                    Dr. Wood is trying to unravel the           On a practical level, Dr.     identifying the pathways
                                       consequences of too much fat.           Wood is particularly concerned    that occur normally. If we
th E PRO B L E M w ith FAt                  “I’m interested in how the         with visceral fat, the extra      can understand the normal
    At Burnham’s Orlando,              body reacts to excess fat and           baggage we may have hanging       processes and how they go
Florida campus, researchers            how fat metabolism and the              over our belts in front.          awry, it will help us find
are focused on the underlying          genetics of fat metabolism                  “Excessive abdominal          ways to reverse or alleviate

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                                                                                           BUrnham DiABEtEs REsEARch

     A National Quest
          Burnham is committed to uncovering the underlying           is more focused on the translational aspects of diabetes.
     mechanisms behind diabetes and finding new ways to treat         Together, we cover the space from the gene, to novel drug
     it. But the Institute is not alone. Burnham has numerous         targets, screens and clinical candidate molecules, followed
     collaborations, large and small, with organizations around       by proof of concept studies in animals and humans. These
     the country that share our desire to beat diabetes. In partic-   are all aimed at delivering innovative cures for diabetes to
     ular, Sanford Health and the Juvenile Diabetes Research          the patient.”
     Foundation (JDRF) are working with Burnham to cure type 1            Both the Sanford Project and Burnham partner with
     diabetes.                                                        JDRF to accelerate the research. Alan Lewis, Ph.D., is
          Paul Burn, Ph.D., is professor of Pediatrics at the         President and CEO of JDRF, which has funded diabetes
     Sanford School of Medicine of the University of South            research at Burnham for many years. JDRF supports research
     Dakota and the Broin Chair and director of the Sanford           into new treatments, as well as new devices.
     Project, a venture sponsored by Sanford Health that seeks            JDRF is also working to help talented researchers, such
     to develop new therapies for type 1 diabetes as quickly as       as Drs. Fred Levine and Pam Itkin-Ansari, and recruit
     possible. Dr. Burn notes that the collaboration between          young scientists.
     Burnham and the Sanford Project bridges the gap between              “We need to encourage researchers to go into the field
     basic and clinical research.                                     by giving them seed funding, as well as a sense they can
          “The capabilities of Burnham and Sanford nicely             partner with JDRF,” says Dr. Lewis. “This research takes
     complement each other,” says Dr. Burn. “Burnham’s                time, and we want researchers to know they will have the
     strengths lie in the early phases of discovery, while Sanford    support they need.”

the complications of the            Osborne. “All these pathways
disease itself.”                    have common nodes. We
     The collaboration between      want to bring this knowledge
Drs. Wood and Osborne               together to understand how
is typical of the Institute’s       these mechanisms function.”
approach to research—
different labs investigate pieces   t h E L ANGUAGE OF FAt
of the larger puzzle and pool           Traditionally, people have
their knowledge. As director        thought of fat as being a
of the Metabolic Signaling          relatively passive part of the
and Disease Program at Lake         body. But fat is no innocent
Nona, Dr. Osborne is eager to       bystander. Researchers are
recruit new scientists who will     learning more about how fat
carry on that tradition.            signals other areas of the
     “Right now, we are             body, including the brain.
working to integrate people         Devanjan Sikder, Ph.D., is
who study various cellular          looking at how these signals
signaling pathways,” says Dr.       can affect both biological
                                                                                                                                           Dr. Devanjan Sikder

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BUrnham DiABEtEs REsEARch

processes and perceptions                incentive to stop eating. This
of food.                                 may be one reason why it
    Dr. Sikder studies the               can be so difficult for obese
hormone orexin, which                    people to lose weight.”
controls hunger and sleep/
                                         M OV i N G D i s c OV E R i E s
wake cycles. High glucose
                                         F O R wA R D
after a meal reduces orexin
                                             Steve Gardell, Ph.D.,
levels and the activity of
                                         director of Translational
orexin-producing neurons,
                                         Research Resources, came
making us feel sluggish.
                                         to Burnham Lake Nona to
Plunging glucose levels,
                                         help move basic science
following overnight fasting,
                                         discoveries from the labora-
elevate orexin, which wakes us
                                         tory to the clinic. With more
to find food.
                                         than 20 years experience in
    The cyclic waxing and
                                         the pharmaceutical industry,
waning of orexin appears
                                         Dr. Gardell understands the
to be perturbed in type 2
                                         challenges of translating
diabetes, obesity and even
                                         basic scientific knowl-
cancer. “Several epidemio-
                                         edge into new medicines.
logical studies have reported
                                         However, he sees many
a correlation between lower
                                         opportunities in the work                                                                Dr. Layton Smith
orexin levels and a higher               being done at Burnham.              burgeoning young discipline       provide great clinical benefit
incidence of obesity and type                “My job is to help shep-        to create new diagnostics.        with few side effects.
2 diabetes,” says Dr. Sikder.            herd some of these incredible
                                                                                 “Metabolomics is a                “Medicine has done
                                                                             powerful way to identify          all the easy things,” says
          “Metabolomics is a powerful way to                                 disease markers that could        Layton Smith, Ph.D. “It’s
                                                                             lead to new tests and early       not that difficult to knock
identify disease markers that could
                                                                             detection,” says Dr. Gardell.     out a protein. Vioxx (an anti-
    lead to new tests and early detection,”                                      Dr. Gardell will also         inflammatory drug that was
              says Dr. Gardell.                                              be working closely with           pulled from the market due
                                                                             Drs. Gregory Roth and             to increased risk of heart
                                                                             Layton Smith to screen for        attack) is a good example. It
    Dr. Sikder is also inter-            discoveries and check them
                                                                             compounds in the Conrad           worked too well because it
ested in how leptin affects              for clinical effectiveness,” says
                                                                             Prebys Center for Chemical        completely knocked out the
the brain. Leptin is a hormone           Dr. Gardell.
                                                                             Genomics. This pain-              Cox2 enzyme. Vioxx created
that controls appetite, telling              One area where Dr.
                                                                             staking process could lead        Cox2-deficient people. So we
us to stop eating. Mice                  Gardell hopes to have a big
                                                                             to new chemical probes to         need to create compounds
without leptin become peril-             impact is metabolomics.
                                                                             illuminate the underlying         that work more subtly. We’ve
ously obese.                             Biochemical reactions
                                                                             mechanisms behind disease         done the chainsaw; it’s time
    “Fat tissue produces                 produce small molecules,
                                                                             and possibly new medicines.       for a scalpel.”
leptin, which tells us to stop           or metabolites, which can
                                                                                 One of the targets they
eating,” says Dr. Sikder. “But           be measured. Dr. Gardell
                                                                             aim for is specificity: finding
if you lose weight, the body             and others at Burnham are
                                                                             the right chemicals that
produces less leptin and                 hoping to capitalize on this
                                                                             influence the exact protein to
you have lost a physiological

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                                                                                                          BUrnham florIda NEws

The    View from Lake Nona
    The landscape outside             Burnham has an incredible
Dr. Daniel Kelly’s office             track record of breaking down
at Burnham’s new Lake                 disciplinary barriers and we plan
Nona campus is a work in              to continue that tradition.”
progress. There is a sandy                 One area Dr. Kelly wants
plain, a few puddles from a           to explore is diabetic heart
recent rainstorm, trees in            disease. He notes that heart
the distance. But Dr. Kelly           failure is not a single condition
sees beyond this temporary            that will respond to one-size-
sparseness to what Lake               fits-all medicines. Researchers
Nona will become as new               and clinicians need to
hospitals, research facilities        understand the underlying
and a university building             distinctions between different
spring up around Burnham.             types of heart disease, so that
                                                                                                      Daniel Kelly, M.D., Scientific Director, Burnham at Lake Nona
                                      the best treatments can be
     He sees multiple collabora-      prescribed based on a clear         can help regulate proteins                clinic. As researchers learn more
tions leading to new insights         understanding of what is going      implicated in disease. In                 about the metabolome (the list
into human biology and new            wrong in the heart.                 addition, the Cardiovascular              of all metabolites), they can
treatments for heart disease,              “Diabetic heart disease is     Pathobiology program at Lake              develop better diagnostic tools.
diabetes, cancer and other            more aggressive and different       Nona will enhance the study of                “There are different kinds of
conditions. He sees Burnham’s         from other forms of heart           fat metabolism, type 2 diabetes,          cancer, and we are very sophis-
basic science and transla-            disease,” says Dr. Kelly. “If we    heart disease and other condi-            ticated in describing them,” says
tional research expertise as a        follow diabetics after a heart      tions. This will be supported by          Dr. Kelly. “But in heart failure,
critical piece of Lake Nona’s         attack and give them the usual      the emerging Cardiometabolic              we lack the sophistication to
burgeoning medical city.              therapies—cholesterol lowering      Phenotyping Core, which will              distinguish between different
     “This is the perfect environ-    drugs, ACE inhibitors—we’ve         diagnose cardiovascular disease           disease types and causes. We
ment to create a truly innovative     found that those treatments         and metabolic disturbances in             just call it heart failure. In our
style of research,” says Dr. Kelly.   don’t work as well. We’re only      small animal models.                      research, we are trying to reca-
“We are already breaking down         beginning to understand that            Dr. Kelly is particularly             pitulate different types of heart
the silos that separate physi-        heart and vascular disease in       excited about the collabora-              failure to find the metabolic or
cians and basic researchers. The      diabetics may have a completely     tion with Duke University’s               genomic signatures that will
Florida Hospital – Burnham            different basis.”                   Stedman Center to establish               help us individualize treatment
Clinical Research Institute (see                                          a metabolomics core facility.             for each patient based on the
article, page 13), along with         LEVERAG i NG                        Every chemical reaction in the            precise nature of their disease.
                                      tE c h NOLOGy
our emerging collaborations                                               body produces compounds                   If we can recognize these signa-
                                          One of Burnham’s trade-
with the University of Central                                            called metabolites, which can             tures, or markers, we will be
                                      marks is the strategic use of
Florida, M. D. Anderson                                                   be measured and catalogued.               able to tell whether a person’s
                                      sophisticated technologies. For
Cancer Center-Orlando, the                                                These markers can help                    heart failure is more related to
                                      example, Lake Nona’s Conrad
Stedman Center at Duke                                                    physicians detect diseases or             diabetes or high blood pressure
                                      Prebys Center for Chemical
University, the University of                                             metabolic defects and test                or heart attack. Physicians will
                                      Genomics, like the facility in
Florida and others will advance                                           treatments for effectiveness.             know the exact condition they
                                      La Jolla, will identify small
science and bring new treat-                                              Metabolomics provides a link              are seeing and that will lead to
                                      molecule compounds that
ments to patients—faster.                                                 between the laboratory and the            innovative treatments.”

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BUrnham sciENcE NEws

Embryology Study Offers
               Clues to Birth Defects
Gregg Duester, Ph.D.,                    limbs. This research corrects
professor in the Develop-                longstanding misconceptions
ment and Aging Program                   about limb development and
at Burnham, Xianling Zhao,               provides new insights into
Ph.D., and colleagues                    congenital limb defects. The
have clarified the role that             study was published online in
                                                                                                                                               Dr. Gregg Duester
retinoic acid plays in limb              the journal Current Biology on
development.                             May 21.
                                                                                      limb patterning but rather is       therapeutic or preventative
                                             “For decades, it was thought
                                                                                      necessary to initiate the limb      measures to combat congenital
    The study showed that                that retinoic acid controlled limb
                                                                                      budding process.”                   limb defects, such as Holt-Oram
retinoic acid controls the               patterning, such as defining
                                                                                          By providing a more             syndrome, a birth defect charac-
development (or budding) of              the thumb as being different
                                                                                      complete understanding of the       terized by upper limb and heart
forelimbs, but not hindlimbs,            from the little finger,” says Dr.
                                                                                      molecular mechanisms involved       defects.
and that retinoic acid is not            Duester. “However, we have
                                                                                      in normal limb development,
responsible for patterning (or           demonstrated in mice that reti-
                                                                                      these findings may lead to new
differentiation of the parts) of         noic acid is not required for

                                                                                      ally” disrupted in mice. This       showed that transgenic mice,
                                                                                      is the first time a conditional     in which Has2 was inactivated
                                                                                      Has2 knockout mouse has             in the limb bud mesoderm,
                                                                                      been created, a breakthrough        had shortened limbs, abnormal
                                                                                      that opens vast possibilities for   growth plates and duplicated
                                                                                      future research. The paper was      bones in the fingers and toes.
                                                                                      published online in the journal         “Because hyaluronic acid is
                                                                                      Development on July 24.             so prevalent in the body, it has
                                               Drs. Kazu Matsumoto and Yu Yamaguchi
                                                                                          HA is a large sugar             been difficult to study,” said Dr.
                                                                                      molecule that is produced by        Yamaguchi. “Systemic Has2
New Insights into              Limb Formation                                         every cell in the body and has
                                                                                      been thought to play a role in
                                                                                                                          knockout mice died mid-gesta-
                                                                                                                          tion and could not be used to
    Investigators at Burnham                 Significantly, these discov-             joint disease, heart disease and    study the role of hyaluronan in
and the University of Connec-            eries were made using a novel                invasive cancers. Yu Yamaguchi,     adults. By inactivating Has2
ticut Health Center (U.C.H.C.)           mouse model in which the                     M.D., Ph.D., a professor in         in specific tissues, we give
have gained new under-                   production of hyaluronan is                  the Sanford Children’s Health       ourselves the opportunity to
standing of the role hyaluronan          blocked in specific tissues. The             Research Center at Burnham          study the many roles hyal-
(also known as hyaluronic acid           Yamaguchi laboratory geneti-                 and Robert Kosher, Ph.D.,           uronan plays in biology. This
or HA) plays in skeletal growth,         cally modified the Has2 gene,                a professor in the Center           mouse model will be useful to
cartilage maturation and joint           which is a critical enzyme for               for Regenerative Medicine           study the role of hyaluronan in
formation in developing limbs.           hyaluronan synthesis, so that                and Skeletal Development            arthritis and skin aging, as well
                                         the gene can be “condition-                  at U.C.H.C. and colleagues          as cancer.”

8   T h e B Urnham repor T |
                                                                                                           BUrnham sciENcE NEws

                                                                            In particular, miR29 plays a           infectivity. The scientists further
                                                                       key role in controlling the HIV             demonstrated that strains of
                                                                       life cycle. The study suggests              HIV-1 with mutations in the
                                                                       that HIV may have co-opted                  region of the genome that
                                                                       this cellular defense mechanism             interact with miR29 are not
                                                                       to help the virus hide from                 inhibited by miR29.
                                                                       the immune system and anti-                     “We think the virus may
                                                                       viral drugs. The research was               use this mechanism to modu-
                                                                       published on June 26 in the                 late its own lifecycle, and we
                                                                       journal Molecular Cell.                     may be able to use this to our
                                                                            The team found that the                advantage in developing new
                                                                       microRNA miR29 suppresses                   drugs for HIV,” says Dr. Rana.
                                                      Dr. Tariq Rana   translation of the HIV-1 genome             “Retroviral therapies greatly
                                                                       by transporting the HIV                     reduce viral load but cannot
MicroRNAs and HIV                                                      mRNA to processing bodies (P-               entirely eliminate it. This
                                                                       bodies), where they are stored              interaction between HIV and
Tariq Rana, Ph.D., director of   RNAs that interfere with              or destroyed. This results in a             miR29 may contribute to that
the Program for RNA Biology      gene expression) reduce HIV           reduction of viral replication              inability. Perhaps, by targeting
at Burnham, and colleagues       replication and infectivity in        and infectivity. The study also             miR29, we can force HIV into
have discovered that specific    human T cells.                        showed that inhibition of miR29             a more active state and improve
microRNAs (non-coding                                                  enhances viral replication and              our ability to eliminate it.”

Carbohydrate Acts as                                                                                               the amount of the glycans,
                                                                                                                   leading to greater move-
       Tumor Suppressor                                                                                            ment by invasive cancer
                                                                                                                   cells. However, when the
                                 the enzyme that produces                                                          researchers forced aggres-
Minoru Fukuda, Ph.D., and
                                 these glycans, β3GnT1,                                                            sive cancer cells to express
colleagues have discovered
                                 results in a significant reduc-                                                   β3GnT1, the laminin-
that specialized complex
                                 tion in tumor activity. The                                                       binding glycans were
sugar molecules (glycans)
                                 research was published July                                                       restored and tumor forma-
that anchor cells into place
                                 6 in the journal Proceedings                                                      tion decreased.
act as tumor suppressors in
                                 of the National Academy of                                                            These results indicate
breast and prostate cancers.
                                 Sciences.                                                                         that certain carbohydrates
                                                                                           Dr. Minoru Fukuda
                                     The specialized glycans                                                       on normal cells and enzymes
    These glycans play a
                                 are capable of binding to                                                         that synthesize those
critical role in cell adhe-                                            from migrating. The team
                                                                                                                   glycans, such as β3GnT1,
sion in normal cells, and        laminin and are attached              demonstrated that β3GnT1
                                 to the α-dystroglycan cell                                                        function as tumor suppres-
their decrease or loss leads                                           controls the synthesis of
                                 surface protein. This binding                                                     sors,” says Dr. Fukuda. “Up
to increased cell migra-                                               laminin-binding glycans
                                 facilitates adhesion between                                                      regulation of β3GnT1 may
tion by invasive cancer                                                in concert with the genes
                                 the epithelium and basement                                                       become a novel way to treat
cells and metastasis. An                                               LARGE/LARGE2. Down-
increase in expression of        membrane and prevents cells           regulating β3GnT1 reduces

                                                                                                        w w w. b u rn h a m . o rg | T h e BU r n h a m r e p o r T
BUrnham sciENcE NEws

  Caspase 8                                                                     toma cancer cells to proliferate
                                                                                and migrate. For the first time,
                                                                                                                   migrate and invade neighboring
                                                                                                                   tissues—a critical process in
and Invasive                                                                    Caspase-8 was shown to play a      cancer metastasis.
                                                                                key role in relaying the growth        “Caspase-8 has a well
      Cancer                                                                    signals from epidermal growth      defined role in promoting
                                                                                factor (EGF) that cause cell       apoptosis, especially in response
Cancer Center director                                                          division and invasion. The         to activation of the so-called
Kristiina Vuori, M.D., Ph.D., and                                               researchers also identified an     death receptors on the outside
colleagues have found that                                                      RXDLL amino acid motif that        of cells,” says Darren Finlay,
the Caspase-8 protein, long                                                     controls the signaling from        Ph.D., first author on the
                                                          Dr. Kristiina Vuori   the EGF receptor through           paper. “Although Caspase-8 is
known to play a major role in
promoting programmed cell                                                       the protein kinase Src to          involved in apoptosis, it is rarely
                                         The study was published in
death (apoptosis), helps relay                                                  the master cell proliferation      deleted or silenced in tumors,
                                     the journal Cancer Research on
signals that can cause cancer                                                   regulator protein MAPK. This       suggesting that it was giving
                                     June 15.
cells to proliferate, migrate and                                               same signaling pathway stimu-      cancer cells a leg up in some
                                         The team showed that
invade surrounding tissues.                                                     lates neuroblastoma cells to       other way.”
                                     Caspase-8 caused neuroblas-

What Makes Stem Cells Tick
Investigators at Burnham             to looking at changes in genes,
and The Scripps Research             we have come to realize that
Institute (TSRI) have made           proteins are the real work horses
the first comparative, large-        and ultimately determine cell
scale phosphoproteomic               behavior,” says Evan Snyder,
analysis of human embryonic          M.D., Ph.D., professor and
stem cells (hESCs) and their         director of Burnham’s Stem
differentiated derivatives.          Cell and Regenerative Biology                                                         Drs. Evan Snyder and Laurence Brill
                                     program. “This study represents
    The data may help stem           the first comprehensive study              Burnham’s Proteomics Facility,     mechanisms that influence self-
cell researchers understand the      of genes being activated during            Dr. Synder and Sheng Ding,         renewal and differentiation.
mechanisms that determine            differentiation and offers predic-         Ph.D., associate professor             “This research will be a big
whether stem cells divide or         tions on cell behavior.”                   at TSRI, catalogued 2,546          boost for stem cell scientists,”
differentiate, what types of cells       Protein phosphorylation,               phosphorylation sites on 1,602     said Dr. Brill. “The protein
they become and how to control       the biochemical process                    phosphoproteins. Prior to this     phosphorylation sites identified
those complex mechanisms             that modifies protein activi-              research, protein phosphoryla-     in this study are freely avail-
to facilitate development of         ties by adding a phosphate                 tion in hESCs was poorly           able to the broader research
new therapies. The study was         molecule, is central to cell               understood. Identification of      community, and researchers can
published in the August 6 issue      signaling. Using sophisticated             these phosphorylation sites        use these data to study the cells
of the journal Cell Stem Cell.       phosphoproteomic analyses,                 provides insights into known       in greater depth and determine
    “While the field of stem cell    the team of Laurence Brill,                and novel hESC signaling path-     how phosphorylation events
biology has become accustomed        Ph.D., senior scientist at                 ways and highlights signaling      determine a cell’s fate.”

10   The B Urnham repor T |
                                                                                                           BUrnham sciENcE NEws

            Cells Respond
        Unraveling How
to Low Oxygen
Gary Chiang, Ph.D., and              expressed in cells under low
colleagues have elucidated           oxygen conditions (hypoxia).
how the stability of the             The Burnham scientists showed
REDD1 protein is regulated.          that the REDD1 protein rapidly
                                     undergoes degradation by the
     The REDD1 protein is a          ubiquitin-proteasome system,
critical inhibitor of the mTOR       which allowed for the recovery
signaling pathway, which             of mTOR signaling once oxygen                                            Drs. Enbo Liu and Gary Chiang and Christine Knutzen
controls cell growth and prolifer-   levels were restored to normal.
ation. The study was published           “Cells initially shut down the   expressing REDD1, which                   REDD1 protein turns over so
in the August 2009 issue of          most energy-costly processes,        inhibits the mTOR pathway. But            rapidly, it allows the pathway
EMBO Reports.                        such as growth, when they’re         when the cell needs the mTOR              to respond very dynamically
     As part of the cellular         under hypoxic stress,” says          pathway active, REDD1 has to              to hypoxia and other environ-
stress response, REDD1 is            Dr. Chiang. “They do this by         be eliminated first. Because the          mental conditions.”

New Faculty
                                                                          research has enumerated the
                                                                          building blocks of the four
                                                                          fundamental components
                                                                          of all cells and combined
JA M Ey MA Rt h , P h . D.           gineering to identify the            them into a research plat-
                                     molecular and cellular origins       form that has revealed
Dr. Marth joins Burnham as           of disease and develop new           pathophysiologic origins of
director of the U.C. Santa           approaches to diagnosis,             autoimmune disease, sepsis
Barbara-Burnham Center               prevention and cure.                 and dietary-induced type 2
for Nanomedicine.                        Dr. Marth’s laboratory           diabetes. The Marth labora-
                                     is known for integrating             tory previously developed                                                   Dr. Jamey Marth

    The center will focus            molecular and cellular biology       the Cre-loxP technology that                  Dr. Marth earned his
on the emerging fields of            as a means to discover               is now used throughout the                Ph.D. in pharmacology from
nanotechnology and bioen-            the origins of disease. His          world as a mainstay technique             the University of Washington,
                                                                          in biomedical research. Dr.               where he worked under Dr.
                                                                          Marth’s discoveries have
         Dr. Marth’s discoveries have spanned                             spanned multiple fields
                                                                                                                    Edwin G. Krebs, a 1992
                                                                                                                    Nobel laureate in medicine
multiple fields including immunology,                                     including immunology, hema-               and Dr. Roger M. Perlmutter,
              hematology, metabolism, oncology,                           tology, metabolism, oncology,             now executive vice president
                                                                          glycobiology, neurobiology
     glycobiology, neurobiology and infectious                                                                      of Research and Development
                                                                          and infectious diseases and               at Amgen.
diseases and are unique in combined                                       are unique in combined
         breadth and accomplishment.                                      breadth and accomplishment.

                                                                                                    w w w. b u rn h a m . o rg | T h e BU r n h a m re p o r T
BUrnham sciENcE NEws

New Faculty continued

                                          tiMOthy OsBORNE, Ph.D.             emphasis on how this influences molecular mechanisms relevant
                                                                             to diabetes and obesity.
                                          Dr. Osborne joins Burnham              Dr. Osborne received his doctorate in microbiology and
                                          at Lake Nona as professor          molecular biology from the University of California, Los
                                          and director of the                Angeles, conducted postdoctoral research at the University of
                                          Metabolic Signaling and            Texas at Southwestern Medical School and was most recently
                                          Disease Program.                   chair of Molecular Biology and Biochemistry at the University
                                                                             of California, Irvine. He has received a Chancellor’s Award
                                             His research seeks to           for mentoring undergraduate research, was recognized as an
                                          understand how the body            Established Investigator of the American Heart Association
                                          senses dietary content to alter    and received a Lucille P. Markey Scholar Award in Biomedical
                   Dr. Timothy Osborne    nutrient absorption with an        Science.

RA N JA N P E R E R A , Ph.D.                 He received his Ph.D. in Molecular Genetics from Moscow
                                          State University and the University of Ghent-Belgium. Dr. Perera
Dr. Perera comes to                       completed his post-doctoral studies in gene targeting and DNA
Burnham from Mercer                       recombination at Massachusetts Institute of Technology. He has
University’s School of                    many years of industry experience and holds numerous patents
Medicine, where he was                    related to gene regulation.
an associate professor                        As an associate professor at Lake Nona, Dr. Perera seeks to
and director of Genomics                  identify prognostic and diagnostic markers for melanoma and will
and research and develop-                 lead Burnham’s analytical genomics lab and establish expertise in
ment at Anderson Cancer                   RNA biology. His research is partly supported by a Department of
Institute.                                Defense grant to study the link between obesity and cancer.
                                                                                                                                  Dr. Ranjan Perera

                                          J ULi O AyAL A , Ph.D.                 Dr. Ayala received his        skeletal muscle. At Burnham,
                                                                             Ph.D. and conducted his post-     he will focus on the control of
                                          An assistant professor             doctoral work in molecular        inter-organ fuel metabolism
                                          at Lake Nona, Dr. Ayala,           physiology and biophysics at      with emphasis on the regula-
                                          comes to Burnham from              Vanderbilt. He has studied        tion of glucose production and
                                          Vanderbilt University School       factors that increase the         utilization. He seeks to reveal
                                          of Medicine, where he was          production and secretion          how metabolic syndrome is
                                          a research faculty member          of insulin. His research has      influenced by errors in sugar
                                          and director of Technology         shown that the hormone            and fat metabolism and to use
                                          Transfer at the Vanderbilt-        GLP-1 affects not only the        those findings to pursue new
                                          NIH Mouse Metabolic                secretion of insulin but also     treatments for diabetes and
                        Dr. Julio Ayala   Phenotyping Center.                insulin action on the liver and   obesity.

12   The B Urnham repor TT ||
      The B Urnham repor
                                                                                                                        BUrnham NEws

        Burnham Chosen for                                                                                novel drug candidates in high-
                                                                                                          risk, under-represented areas of
National Chemical                                                                                         cancer biology.

      Biology Consortium                                                                                      “Burnham’s strategic focus
                                                                                                          for the past five years has been
                                                                                                          on building our capabilities
Burnham has been selected          The consortium will trans-                                             in chemical genomics and
as one of three compre-        late knowledge from leading                                                drug discovery,” says President
hensive centers in a new       academic institutions into new                                             and CEO John Reed, M.D.,
National Cancer Institute      drug treatments for cancer                                                 Ph.D. “The Chemical Biology
(NCI) Chemical Biology         patients. Burnham’s La Jolla                                               Consortium gives Burnham an
Consortium, an integrated      and Lake Nona campuses will      to expedite the development
                                                                                                          additional platform to use our
network of chemical biolo-     both participate.                and distribution of new cancer
                                                                                                          advanced technologies, some
gists, molecular oncologists       The NCI seeks to coordi-     treatments. The consortium
                                                                                                          of which are virtually unprec-
and chemical screening         nate their own drug discovery    will expand current NCI
                                                                                                          edented in the not-for-profit
centers.                       efforts with academic institu-   programs in personalized medi-
                                                                                                          research world.”
                               tions and private companies      cine to identify and advance

                                       Clinical Research                                                  directing the new institute.”
                                                                                                              Florida Hospital will also

                                           Institute Moves Forward                                        build a state-of-the-art, 35,000
                                                                                                          square-foot facility to house
                                                                                                          the Clinical Research Institute.
                                       appointed execu-             “Our vision was to recruit
                                                                                                          Groundbreaking is scheduled
                                       tive director of the     a world-class physician and
                                                                                                          for early 2010. The Institute
                                       Florida Hospital –       scientist to lead our mission,”
                                                                                                          will combine scientists and
                                       Burnham Clinical         says Dr. Daniel Kelly, Scientific
                                                                                                          clinicians with sophisticated
Steven R. Smith, M.D., an      Research Institute, which        Director of Burnham at Lake
                                                                                                          technology to enhance transla-
internationally-renowned       will investigate diabetes,       Nona. “We have found the
                                                                                                          tional research and bring new
diabetes and obesity           obesity and cardiovascular       very best and are delighted
                                                                                                          treatments to patients.
researcher, has been           disease.                         that Dr. Smith will be

Burnham Collaborates with                                       Center’s metabolomics expertise               “Burnham and Stedman
                                                                with Burnham’s complementary              Center scientists will be able
            Duke University                                     technologies.                             to exploit the power of these

         Metabolomics Center                                        The Stedman Center is
                                                                well known for its metabolic
                                                                                                          technologies to define disease
                                                                                                          signatures relevant to diabetes,
                                                                research, particularly metabo-            heart disease, cancer and other
Burnham and the Sarah          of disease and identify          lomic profiling of biological             diseases” says Dr. Daniel Kelly,
W. Stedman Nutrition           biomarkers for diagnosis         samples using mass spectrom-              Scientific Director, Burnham
and Metabolism Center          and treatment.                   etry-based technologies. The              at Lake Nona. “Metabolomic
(Stedman Center) at Duke                                        Burnham-Stedman metabo-                   approaches show great promise
University Medical Center          The agreement will estab-    lomics platform will create               for identifying diagnostic
have announced a new           lish an extension of Duke’s      collaborative opportunities and           markers that will aid clini-
collaboration to use meta-     Stedman Center laboratory at     expand the research capacity              cians in distinguishing disease
bolomic profiling to clarify   Burnham’s Lake Nona campus       of both Duke University and               patterns and in developing
the basic mechanisms           and combines the Stedman         Burnham.                                  individualized treatment plans.”

                                                                                           w w w. b u rn h a m . o rg | T h e BU r n h a m re p o r T
p h I l a n T h r o p y U P D At E

Burnham Welcomes                                                                                              director of development for
                                                                                                              the College of Engineering
         Julie Johnson                                                                                        at the University of Florida,
                                                                                                                  “I’m excited to be part
   Lake Nona’s new asso-             Association (MDA) over the
                                                                                                              of Burnham at Lake Nona,”
ciate director for external          summer and that’s where the
                                                                                                              says Johnson. “My sister died
relations Julie Johnson is           love affair began.”
                                                                                                              from a heart attack at 47
a seasoned development                   Johnson graduated with
                                                                                                              as a result of uncontrolled
professional with more               a degree in journalism and
                                                                                                              type 2 diabetes. Obesity and
than 26 years experience.            continued with the MDA
                                                                                              Julie Johnson   diabetes are challenging health
                                     as an events coordinator.
                                                                                                              issues, and I am certain that
    “I became interested in          Later, she served as assistant   Florida; regional vice president        researchers at Burnham will
nonprofit work when I was            executive director for the       of the Arthritis Foundation of          make significant discoveries
a student at the University          Leukemia and Lymphoma            Northeast Florida; president            that will advance our ability to
of Florida,” says Johnson.           Society; president and           of Expedition Inspiration               treat them.”
“I had an internship with            CEO of the Mental Health         Fund for Breast Cancer
the Muscular Dystrophy               Association of Northeast         Research and, most recently,

                                                                      to the buyer without gift tax cost. If the asset is depressed real
            Estate Planning In                                        property selected with location in mind, it likely will come back

Challenging Times                                                     eventually. Allow children to capture the recovery by selling it to
                                                                      them now.
                                                                          Outright gifts while values are depressed are even better than
Ken G. Coveney, Esq.
                                                                      sales. If a parent sells to a child (or a trust for the child’s benefit),
Burnham Planned Giving Advisory Council
                                                                      and if the sale price is less than the parent’s basis, the parent’s loss
                                                                      on sale will be disallowed, but the child (or trust) will be stuck
    Every cloud has a silver lining. We have been in difficult
                                                                      with lower basis. If the parent gives the property to the child (or
economic times for awhile, but most people remain opti-
                                                                      trust), the recipient will take the donor’s higher income tax basis
mistic about the future. Now is the time to take advantage
                                                                      for purposes of computing gain when they dispose of the property.
of these circumstances.
                                                                          Consider transfers in trust with remainder interests to chil-
                                                                      dren or the Burnham Institute for Medical Research. If a donor
    Interest rates are near historic lows. Make loans to children
                                                                      transfers assets to a grantor retained annuity trust (GRAT), the
and grandchildren or trusts for their benefit. A loan at the
                                                                      value of the retained annuity interest will be higher in this low
applicable federal rate (AFR) for long-term loans (more than
                                                                      interest environment.
nine years) is 4.33 percent. A loan at the AFR is not a gift. If
                                                                          Similarly, if a donor transfers assets to a charitable lead annuity
the children/borrowers can obtain a higher return than the AFR,
                                                                      trust (CLAT), the value of the annuity interest given to the
they will reap future value at no transfer tax cost to the parents/
                                                                      Burnham will be higher in this low interest environment and the
lenders. If the parents see a good investment opportunity, they
                                                                      value of the remainder interest gifted to the children will be lower.
can allow the children to capture it by lending them the funds to
                                                                      Remember, in both a GRAT and a CLAT, the present value of the
acquire the investment.
                                                                      remainder interest is what counts for gift tax purposes.
    Installment sales use the same interest rates as loans. A sale
                                                                          So don’t surrender!! The iron is hot; now is the time to strike.
of an appreciating asset transfers the appreciation from the seller

14   The B Urnham repor T |
                                                                                                               p h I l a n T h r o p y U P D At E

    The    Chair-iot Society
       Just as the ancient              state-of-the-art audi-                                                     For more information,
    chariot was critical to             torium. Membership                                                     please call 407-745-2061.
    warfare, Burnham’s                  in the Chair-iot
    Chair-iot Society seeks to          Society is $1,000                                                                  SPONSORS
    battle disease by raising           and entitles you                in Central Florida,” says Dr.
    funds and awareness of              to annual briefings about       Nicole Beedle. “And as a
    Burnham’s mission.                  Burnham’s cutting edge          doctor, I am personally proud
                                        science at the Lake Nona        of the research going on in
        Please consider being           campus.                         Orlando.”
    an inaugural supporter of               “As Florida natives,            The Chair-iot Society
    Burnham at Lake Nona by             my husband and I were           will host an Unveiling Event
    placing your name on one            excited to be able to put our   October 9, 2009 at 7 p.m.
    of the 201 chairs in our            name on the future of science

Team Burnham                                                            professional training, race gear by Brooks, personal shoe fittings and
                                                                        discounts at Fleet Feet, all race weekend accommodations, local
                                                                        transportation, all meals, a one-day Disney pass and the only cour-
wA Lt D i sN Ey wO R LD , O RL ANDO , F LOR i DA
                                                                        tesy RV at the finish line.
JA N UA Ry 9 A N D 10 , 2010
                                                                            To become a member of Team Burnham, please contact Kathy
    Team Burnham for Medical Research will be running                   Pierson at 407-595-8099 or log onto
the Walt Disney World Half Marathon & Marathon to raise
support for Burnham’s cutting-edge biomedical research.
Regardless of age or experience, we welcome all runners to
join us and run for discovery.

    Our coaches have put together a training program that can get
anyone over the line for either the half (13.1 miles) or full (26.2
miles) marathons. Or, if you are feeling Goofy, you can do both —
and there is still time to join.
    “I had never run a step in my life, and certainly never thought
I could run a half marathon,” says Catlin Potter Valmont, who           GOLD
is returning for her second half marathon. “Training with Team          SPONSORS
Burnham was the inspiration I needed to get into shape and
complete what I thought to be impossible.”
    Each team member raises $2,500 to fund Burnham research,
with the overall goal of raising more than $150,000. The top
fundraiser will receive two free tickets anywhere AirTran flies. All    SILVER
participants will have their own fundraising page and will receive      SPONSORS

                                                                                                   w w w. b u rn h a m . o rg | T h e BU r n h a m re p o r T
p h I l a n T h r o p y U P D At E

        The Power to Cure
                       Gala 2009
         Saturday, November 14, 2009
         Hyatt Regency La Jolla Aventine
                  6:00 pm          Cocktail Reception
                  7:00 pm          Dinner, Auction, Dancing

                                                                         This award-winning image of Osteoclasts was produced by Dr. Melanie Hoefer in the Rickert laboratory.

    The basic biomedical              inspiring images taken directly   and inflammatory, neurode-                           and lead sponsors include
research at Burnham produces          from the research bench.          generative and childhood                             Jeanne and Gary Herberger,
knowledge, treatments and                                               diseases. The live auction will                      Roberta and Malin Burnham
                                      sNEA k P EE k
even art. Co-chaired by                                                 feature a jet trip and dinner                        and Peggy and Peter Preuss.
                                          The Fund-A-Need will
Caroline Nierenberg and                                                 in Napa Valley, a dinner party                           The Burnham Gala sells
                                      support talented young
Kathryn Stephens, this year’s                                           at Pamplemousse Grille and                           out every year, so be sure
                                      scientists and help purchase
gala celebrates the art of                                              an internship with John C.                           to reserve your seats today.
                                      essential technology to
science, as the ballroom will                                           Reed, M.D., Ph.D, Burnham                            Tickets and sponsorship
                                      enhance Burnham research on
be transformed into a gallery of                                        President and CEO,                                   opportunities are still avail-
                                      cancer, as well as infectious
                                                                        Professor and Donald Bren                            able. For more information,
                                                                        Presidential Chair.                                  please contact Chelsea Jones
“The art and science of asking questions is the                             This year’s presenting                           at 858-795-5239 or cjones@
source of all knowledge.”           —Thomas Berger                      sponsor is Life Technologies               

                                                                                                                         Each year, the Fishman Fund
                                                                                                                      Award, established in honor of
                                                                                                                      Dr. William and Lillian Fishman,
                                                                                                                      recognizes a group of outstanding
                                                                                                                      postdoctoral fellows for their
                                                                                                                      hard work and scientific vision.
                                                                                                                      Burnham and the Fishman Fund
                                                                                                                      cordially invite you to this year’s
                                                                                                                      reception to recognize the 2009
                                                  Thursday, October 15, 2009                                          Award recipients.
                                                           5:30 pm                                                       Please RSVP by October 12
                                                                                                                      to Wendy Sunday at wendys@
                                               at Burnham Institute for Medical Research                     or 858-646-3100,
                                                10901 North Torrey Pines Road, La Jolla                               extension 3420.

                                              hELPiNG yOUNG REsEARch sciENtists sO thEy cAN hELP thE wORLD

16   The B Urnham repor T |
                                                                                                                   presIdenT’s MEssAGE

Scientific     Excellence Fuels Strong Growth
   In our 33rd year, Burnham has surpassed significant milestones in scientific achievement,
research staffing and infrastructure development. As of July 1, the Institute exceeded 1,000
employees, including 74 full-time faculty and 800 scientific staff.
   With the opening of Burnham’s Lake Nona campus in Orlando, Florida, the acquisition of
an additional research building in La Jolla, California and the creation of the joint Center for
Nanomedicine with the University of California, Santa Barbara, we have increased our space
from 382,000 square feet in January 2009 to more than 671,000 square feet today. This continued
growth is creating many opportunities to expand the boundaries of scientific knowledge and                   John C. Reed, M.D., Ph.D.
increase employment opportunities during these challenging times.                                            President and CEO
   Although we are growing rapidly, we have also maintained strong attention to quality, as                  Professor and Donald Bren
evidenced by Burnham’s number one ranking for the past decade in scientific journal citations per               Presidential Chair
publication in the fields of biology and biochemistry among all organizations worldwide.
   In the past two years alone, the Institute has published more than 600 research papers in
scientific journals. These papers advanced understanding of the mechanisms underlying cancer,
Alzheimer’s, HIV, diabetes and many other conditions. Among many recent advances, Burnham
researchers have helped discover monoclonal antibodies that attack a variety of flu strains, illumi-
nated how HIV co-opts cellular mechanisms to create persistent infections, devised novel chemicals
                                                                                                             In the past two years
that attack anti-death proteins responsible for sustaining malignant cells and thus providing a
means to kill chemoresistant cancer cells, elucidated how protein misfolding and protein oxidation
                                                                                                             alone, the Institute
         15.	 John	Reed	essay	                                                                               has published more
contribute to the demise of brain cells in Parkinson’s, Alzheimer’s and other neurodegenerative
diseases and generated replacement heart cells from synthetically-produced stem cells as a new               than 600 research
approach to treating heart attack and heart failure.                                                         papers in scientific
   We have also increased our overall grants and contract revenue. We are the only organization
                                                                                                             journals. These
in the nation to achieve more than five consecutive years of growth in funding from the National
Institutes of Health (NIH), averaging 11.5 percent annual growth for the past 8 years. Last year,
                                                                                                             papers advanced
Burnham received a $98 million contract from the NIH to support a national network in chemical               understanding of
genomics, as well as an $8 million NIH grant to establish a national Parkinson’s disease research            the mechanisms
center. While covering more than 90 percent of costs from competitive grants, we have also                   underlying cancer,
secured important philanthropic gifts to help accelerate our research programs. South Dakota                 Alzheimer’s, HIV,
banker T. Denny Sanford donated $20 million to create the Sanford Children’s Health Research
                                                                                                             diabetes and many
Center, San Diego developer Conrad Prebys gave $10 million to name the Conrad Prebys Center
for Chemical Genomics and Irvine Companies owner Donald Bren contributed $2.5 million to
                                                                                                             other conditions.
create the Donald Bren Presidential Chair at Burnham.
   At Burnham, our motto is From Research, the Power to Cure. By adding more scientists to our
team and providing them with additional laboratory space, we hope to accelerate our efforts to trans-
late basic science discoveries into better treatments that reduce human suffering around the world.

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 6400 Sanger Road                                                the Burnham institute
 Orlando, FL 32827


                                                                in Science:
                                                                    Denny Sanford

                                                                and Dr. Fred Levine

                                                                Denny Sanford wants to help
                                                                medical scientists cure type 1
                                                                diabetes in his lifetime. He has
                                                                created the Sanford Project to
                                                                achieve this goal. Fred Levine,
                                                                M.D., Ph.D., director of Burnham’s
                                                                Sanford Children’s Health Research
                                                                Center, is also working to find a
                                                                cure. Both a research scientist and
                                                                a practicing physician, Dr. Levine
                                                                knows well the suffering type 1
                                                                diabetes can cause. His laboratory

   “Injected insulin does not cure type 1 diabetes,”            is investigating new ways to replace
                                                                insulin-producing beta cells, either
                 says Denny Sanford. “But by gathering the      through transplants or regeneration.
       best scientific minds to investigate the immune system
          and beta cell regeneration, we will find a cure.”

                                                                    Printed on recycled paper

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