REPORT TO INVESTORS 2009

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REPORT TO INVESTORS 2009 Powered By Docstoc
					REPORT TO INVESTORS 2009
Profound questions answered through
scientific research are key elements in the
search for ways to treat, cure and ultimately
prevent childhood diseases and illnesses.

The Children’s Discovery Institute is a
world-class center for pediatric research
and innovation created to encourage
researchers to ask bold questions and
take bold risks to uncover answers.




Contents
Page	 2	 “Lab	Notes”	from	the	Children’s	Discovery	Institute
Page	 6	 The	Grant	Award	Process
Page		 8	 Funding	Categories
Page	 9	 Awards,	2007	to	2009
Page	 17	 Leadership	and	Boards
To our partners
  St.	Louis	Children’s	Hospital’s	standing	as	a	national	leader	in	pediatric	medicine	
is	founded	in	more	than	a	century	of	partnership	with	Washington	University	School	
of	Medicine,	one	of	the	leading	research,	teaching	and	patient	care	institutions	in	the	
nation.	Both	entities	share	a	deep	commitment	to	patients	and	their	families,	coupled		
with	a	passion	for	achieving	the	scientific	breakthroughs	that	give	them	hope.
  Since	2006,	the	Children’s	Discovery	Institute	has	embodied	this	shared	dedication	
thanks	to	an	important	partner	–	the	individuals	whose	generous	gifts	fund	our	purposes.	
The	Children’s	Discovery	Institute	takes	the	hospital	–	and	its	supporters	–	to	a	level	of	
commitment	to	children’s	health	that	is	unmatched.
  Our	intent	for	this	report	is	to	give	our	donor	partners	information	about	what	the	
Children’s	Discovery	Institute	expects	from	its	investigators,	a	look	at	how	it	operates,	
and	most	of	all,	what	this	unique	partnership	has	achieved	in	just	three	years.




                             Alan	L.	Schwartz,	MD,	PhD
                             Executive	Director,		
                             Children’s	Discovery	Institute




                             Lee	F.	Fetter
                             President,		
                             St.	Louis	Children’s	Hospital




                                                                                            	
                                                     childrensdiscovery.org		|		314.286.0988	   
            By its very definition, science is limited to
            what can be observed, measured and verified.
            The “scientific method” represents a rigorous process for observing, exploring and answering questions about cause and effect
            relationships in nature. Experiments are designed so that changes to one item cause something else to vary in a predictable manner.
            Since its inception three years ago, the Children’s Discovery Institute, along with the investigators it funds, has followed this process.


            Creation of the Institute began with the observation that:                             By	February	of	2009,	the	Institute	had	funded	the	52	awards	
            •	 	 oung	researchers	with	bold	ideas	are	often	the	ones	
               Y                                                                                   described	in	this	report.	Primary	investigators	and	their	
                who	make	key	discoveries.                                                          collaborators	–	more	than	100	scientists	in	all	–	are	at	work	
            •	 	 hese	same	researchers	are	often	overlooked	when	it	
               T                                                                                                                       	
                                                                                                   on	these	projects.	Over	100	scientific	papers	about	their	work	
                comes	to	funding.                                                                  have	been	published	or	accepted	for	publication	by	prestigious	
            •	 	deas	generated	by	collaborations	that	cross	traditional	
               I                                                                                           	
                                                                                                   scientific	journals.	The	seed	investment	provided	by	the	Institute	
                departmental	boundaries	often	yield	monumental	results.                            has,	so	far,	garnered	more	than	$12	million	in	additional	
                                                                                                   funding	to	our	investigators.
            A hypothesis was developed:
            If these researchers have seed money to start their projects,                          By	the	end	of	March,	2009,	eight	of	the	investigations	had	
            a portion of them will progress to the point of attracting                             been	concluded.	A	listing	of	awards	begins	on	page	8.	
            greater funding. Of those who attract more funding, a portion
            will make key discoveries that result in improved treatments,                          What follows on the next few pages are some excerpts
            preventions, or even cures for childhood diseases.                                     from the Children’s Discovery Institute’s “laboratory
                                                                                                   notebook” about how the experiment is proceeding.
            The Children’s Discovery Institute is in the midst of
            an experiment to verify that hypothesis.
                	




                    Uncovering genetic causes of disease
                                                                                   Investigator	Ashley Hill, MD,	and	collaborators	announced	in	April	that	
                                                                               children	with	the	cancer	pleuropulmonary	blastoma	(PPB),	a	rare,	aggressive	
                                                                               childhood	lung	cancer,	are	born	with	a	deleterious	mutation	in	DICER1	–	
                                                                               a	master	controller	gene	that	helps	regulate	the	expression	of	other	genes.	
LAB NOTES




                                                                                   About	40	percent	of	PPB	cases	occur	in	families	with	a	history	of	the	
                                                                               disease	or	certain	other	childhood	cancers.	Most	pediatric	cancers,	in	con-
                                                                               trast,	occur	sporadically,	without	any	familial	patterns.	This	led	scientists	and	
                                                                               doctors	to	suspect	that	PPB	was	caused	by	an	inherited	genetic	abnormality.	
                                                                                   To	uncover	the	role	of	DICER1,	the	research	team	studied	the	genetic	
                                                                               makeup	of	11	extended	families	with	two	or	more	members	having	PPB	or	
                                                                               related	childhood	cancers.	This	discovery	uncovered	important	information	
                                                                               about	how	the	cancer	develops	and	potentially	sheds	light	on	the	development	
                                                                               of	other	cancers.




            2        CHILDREN’S	DISCOVERY	INSTITUTE		|		REPORT	TO	INVESTORS	2009
                   In	2008,	Faculty	Scholar Christina Gurnett, MD, PhD,	and	collaborator	
                 Matthew Dobbs, MD,	found	the	first	gene	linked	to	clubfoot	in	humans.	
                                               	
                 Gurnett	analyzed	the	DNA	of	35	extended	family	members	of	an	infant	
                 male	patient	of	Dr.	Dobbs,	a	clubfoot	specialist,	and	traced	the	condition	to	
                 a	mutation	in	a	gene	critical	for	early	development	of	lower	limbs	called	PITX1.
                                                                                        	
                   While	other	genes	are	also	likely	to	be	linked	to	clubfoot,	the	new	finding	
                 is	an	exciting	step	in	developing	a	better	understanding	of	the	genetic	basis	
                 of	clubfoot,	which	affects	about	1	in	1,000	new	births.
                   Identifying	the	genes	for	clubfoot	will	allow	for	improved	genetic	counseling	
                 and	may	potentially	lead	to	new	and	improved	treatment	and	preventive	
                 strategies	for	this	disorder.


                   Germs	in	the	human	body	outnumber	cells	ten	to	one	–	and	most	of	these	
                 bacteria	reside	in	the	gut.	Intestinal	bacterial	colonization	begins	in	the	
                  	
                 first	year	of	life,	and	these	microbes	are	thought	to	play	a	role	in	diseases	
                 including	obesity,	diabetes,	asthma,	and	autoimmune	disorders.	
                   Washington	University	Investigators,	Phillip Tarr, MD, and	Barbara
                 Warner, MD, have	asked	the	question:	“To	what	extent	do	genetics	affect	
                 the	composition	of	the	bacteria	in	an	individual’s	intestines?”
                   To	answer	this	question,	sets	of	infant	twins,	along	with	their	mothers,	are	
                                                                      	
                 being	recruited	to	provide	stool	samples	during	the	first	year	following	birth.	




                                                                                                              LAB NOTES
                 Drs.	Tarr	and	Warner	are	using	new	molecular	technology	methods	to	gain	
                 insights	about	how	this	vibrant	bacterial	“biomass”	develops.
                   This	project	will	provide	revolutionary	data	about	the	effects	of	human	
                 genes	on	bacterial	content	that	will	form	the	basis	for	other	studies	on	the	
                 role	of	early	microbial	colonization	and	childhood	health.




Developing new technologies
                   Investigating	a	“rare	gene	variant”	hypothesis	for	why	children	develop	
                 cancer	led	investigators	Todd Druley, MD, PhD,	and	Robi Mitra, PhD,	
                 to	design	a	new	method	to	comprehensively	screen	a	common	pool	of	DNA	
                 from	over	1,000	individuals	for	rare	inherited	mutations.	
                   Such	an	analysis	was	too	costly	and	time-consuming	to	be	feasible	until	Drs.	
                 Druley	and	Mitra	combined	the	latest	DNA	sequencing	technology	available	
                 at	Washington	University	with	“home-grown”	unique	computer	programming	
                 able	to	accurately	sift	through	the	massive	volumes	of	data	produced.
                   The	investigators	are	also	applying	their	breakthrough	methods	in	the	
                 ability	to	identify	rare	but	important	variants	of	disease	to	other	Children’s	
                 Discovery	Institute	projects,	including	newborn	lung	disease,	children	born	with	
                 clubfoot,	inherited	lung	disease	in	older	children,	and	pediatric	heart	failure.
                   Their	work	was	published	in	Nature Methods	in	March	2009.




                                                                                                      	
                                                               childrensdiscovery.org		|		314.286.0988	   3
                                                                       Collaborating to Make the Possible
                                                                       Probable for Children with Cancer
                                                                       In the future …
                                                                       doctors will be able to determine when a child’s
                                                                       body is at peak readiness for cancer treatment.
                                                                       Therapy will include a precision strike force of
                                                                       nanoparticles that will home in on tumors, “dock”
                                                                       with malignant cells, and insert their killer payloads
                                                                       before harmlessly exiting the child’s body – leaving
                                                                       no “collateral damage” to normal cells.




    Nanoparticles	—	unimaginably	small	structures	a	billion	times	shorter	than	
                 	—	unimaginably	small	structures	a	billion	times	shorter	than	
a	yardstick	–	have	the	potential	to	revolutionize	brain	cancer	research	and	
treatment.	These	tiny	packages,	designed	with	internal	compartments	to	hold	
medicines	as	well	as	substances	that	can	be	scanned	with	medical	imaging	
devices,	are	small	enough	to	cross	the	blood-brain	barrier.	
    Once	inside,	chemical	“hooks”	on	the	outside	of	nanoparticles	can	
locate	and	bind	to	cancer	cells.	When	attached,	the	nanoparticles	
release	their	deadly	contents,	killing	the	cancer	cells	and	leaving	the	
healthy	cells	unharmed.
    With	her	2007	Children’s	Discovery	Institute	grant,	Karen Wooley, PhD,	
and	her	colleagues,	developed	three	types	of	nanostructures	that	can	incorporate,	
and	then	release,	a	common	chemotherapeutic	agent.	They	also	demonstrated	that	the	
tiny	structures	can	recognize	and	bind	to	malignant	tumors	implanted	into	the	brains	
of	mice	–	key	milestones	in	the	quest	for	better	treatment	of	pediatric	brain	tumors.




               Institute Investigator,	Sheila Stewart, PhD,	collaborated	in	the	nanoparticle	
                                                           	collaborated	in	the	nanoparticle	
            investigation	by	manipulating	the	surface	components	of	experimental	cancer	cells	
            to	test	the	ability	of	nanoparticles	to	recognize	the	cells.	
               Dr.	Stewart	is	also	responsible	for	the	Children’s	Discovery	Institute	Core	
            Facility	devoted	to	Viral Vector-Based RNA Interference.	RNA	Interference	(RNAi)	
            is	a	technology	that	allows	the	selective	manipulation	of	gene	expression	in	
            human	cells,	and	is	being	used	with	cancer	cells	derived	directly	from	children	
            with	pediatric	brain	tumors	—	cells	made	available	by	the	Children’s	Discovery	
            Institute	Brain	TumorBank.




4        CHILDREN’S	DISCOVERY	INSTITUTE		|		REPORT	TO	INVESTORS	2009
                                                                            disease,
                                        Developing reliable mouse models of disease,	such	as	those	used	in	the	nanoparticle	
                                          investigation,	is	essential	for	drug	development	and	testing.	Washington	University	neurosurgeon	
                                                           MD,
                                             Jeff Leonard, MD,	who	did	the	biological	work	on	the	nanostructure	project,	is	an	expert	
                                                                	
                                               in	growing	specific	tumor	cell	types	and	implanting	cells	and	tumor	tissues	into	mouse	brains	
                                               that	closely	and	reliably	mimic	human	biology.	
                                                   In	2007,	Dr.	Leonard	started	the	Children’s Discovery Institute Brain TumorBank	to	collect	
                                                tumor	tissue	specimens	and	associated	patient	data	for	research	into	pediatric	brain	cancers.	
                                               Samples	from	this	TumorBank	are	available	to	cancer	researchers	at	Washington	University.




  Malignant cells from the TumorBank                                                                are	in	the	response	to	a	brain	tumor	between	
grafted into mice	are	helping	investigator	                                                            different	regions	of	the	brain.
Josh Rubin, MD, PhD,	learn	how	tumor	growth	                                                                Dr.	Rubin	is	also	collaborating	in	another	
is	affected	by	the	brain	tissue	surrounding	the	                                                          investigation	to	study	cell	response	to	various	
tumor.	In	this	research,	funded	in	2009,	Dr.	Rubin	                                                       chemotherapeutic	drugs	when	given	at	
is	using	proteomic analysis,	a	technology	that	will	                                                      different	times	according	to	the	“Circadian	
help	determine	how	the	presence	of	a	brain	tumor	                                                         Rhythm”	exhibited	by	the	cells.
changes	the	brain	around	it	and	what	the	differences	




  Proteomics	is	the	large-scale	study	of	the	structures	                                     Erik Herzog, PhD,	shares	Dr.	Rubin’s	opinion	that	
and	functions	of	proteins	and	how	the	assemblage	of	                                       each	child’s	body	may	have	a	best	time	of	day	for	killing	
proteins	differs	from	cell	to	cell	and	from	time	to	time.	                                 cancer	cells,	as	well	as	a	best	time	of	day	to	rid	itself	of	
In	2008,	the	Children’s	Discovery	Institute	helped	                                        the	side	effects	of	drugs.	The ability to deliver cancer
fund	a	new	Proteomics Core	platform	at	Washington	                                         treatments in synch with a child’s circadian
University’s	Proteomics	Center	directed	by	Investigator	                                   rhythm – the	natural	changes	in	biological	processes	
Reid Townsend, MD. Proteomics	studies	enable	                                              that	occur	during	a	24-hour	period	–	may	minimize	side	
investigators	from	all	Discovery	Institute	Centers	to	                                     effects	and	allow	for	more	aggressive	treatment.	
                                                   	
correlate	the	vast	array	of	potential	protein	modifications	that	                          Dr.	Herzog’s	2008	Children’s	Discovery	Institute	grant	
take	place	within	cells	to	the	particular	issue	being	studied.                             is	enabling	him	to	study	this	issue.




                                                                                                                                          	
                                                                                                   childrensdiscovery.org		|		314.286.0988	       5
   Award Process
                                                          Idea to Award



           Letter of Intent




 Review by Executive Director/
       Scientific Director




    Invitation for Proposals
                                                             Since the first grants were awarded in 2007,	the	Children’s	Discovery	Institute	
                                                          has	funded	approximately	25	percent	of	grant	requests	received.	
                                                             The	pathway	to	a	Children’s	Discovery	Institute	award	begins	with	a	Letter	of	Intent,	which	
                                                          briefl	y	states	the	problem	an	investigator	wishes	to	pursue	and	how	the	knowledge	gained	
                                                                     	
                                                          might	benefit	children’s	health.	These	letters	are	accepted	twice	each	year.
                                                                                                                                  	
                                                             The	Letters	of	Intent	are	reviewed	by	the	Executive	Director/Scientific	Director,	who	
                                                          invites	investigators	with	the	most	promising	ideas	to	submit	full-blown	proposals	for	
                                                          further	consideration.
       Submit Proposal                                       Proposals,	which	include	detailed	plans	and	budgets,	bio-sketches	of	key	personnel,	and	
                                                                                                                     	
                                                          letters	of	support,	are	reviewed	by	members	of	the	Scientific	Advisory	Board	during	fall	and	
                                                          spring	meetings.
                                                                         	
                                                             The	Scientific	Advisory	Board’s	recommendations	about	projects	that	merit	funding	are	
                                                          then	presented	to	the	Board	of	Managers,	which	meets	four	times	each	year.	Charged	
                                                                                                                           	
                                                          with	determining	the	level	of	funding	available,	this	board	has	final	approval	of	the	grants	
                                                          to	be	funded.
Review and Recommendation by
    Scientific Advisory Board
                                                             Awards	are	announced	in	January	and	June.	Awardees	are	expected	to	comply	with	
                                                          rigorous	accounting	and	reporting	requirements	throughout	the	duration	of	the	grant.




        Approval by
     Board of Managers




       6             CHILDREN’S	DISCOVERY	INSTITUTE		|		REPORT	TO	INVESTORS	2009
Awards are made within four Centers of Focus
           Congenital Heart Disease Center

                                                                                         22                        24
           McDonnell Pediatric Cancer Center
                                                                                                   %
                                                                                         24                        30
           Center for Pediatric Pulmonary Disease


                                                                                             Award Dollars by Center
                                                                                            (January, 2007 — July, 2009)
           Center for Musculoskeletal and Metabolic Diseases




Grants Encompass Multiple Disciplines
Fourteen departments at Washington University have received funding from
                                             .
the Children’s Discovery Institute since 2007 Numbers in parentheses denote
total grants awarded.

                                                                          Biology (3)

                                                                          Biomedical Engineering (1)

                                                                          Cell Biology & Physiology (1)

                                                                          Chemistry (1)

                                                                          Computer Science & Engineering (1)

                                                                          Developmental Biology (1)

                                                                          Genetics (5)

                                                                          Internal Medicine (6)

                                                                          Molecular Microbiology (2)

                                                                          Neurology (2)

                                                                          Neurosurgery (2)

                                                                          Obstetrics & Gynecology (1)

                                                                          Orthopedic Surgery (2)
                        Number of Awards by Department
                           (January, 2007 — July, 2009)
                                                                          Pathology & Immunology (2)

                                                                          Pediatrics (22)


                                                                                                                     	
                                                                              childrensdiscovery.org		|		314.286.0988	     7
Funding Categories
Interdisciplinary Research Initiatives: $6,950,000
Provide	up	to	$450,000	to	a	primary	investigator	and	team	of	colleagues		
to	research	a	specific	question	within	one	of	the	Institute	Centers.


Large Initiatives: $5,750,000
Provide	up	to	$1,500,000	to	support	shared	core	resources	or	to	bring		
important	technologies	to	the	research	efforts	within	the	Institute.


Faculty Scholar Awards: $1,000,000
Provide	start-up	funding	of	up	to	$300,000	to	select	new	faculty	members		
at	the	Washington	University	School	of	Medicine	to	enable	them	to	set	up		
a	laboratory	and	begin	a	project	in	pediatric	medical	research.


Fellowships: $270,000
Provide	up	to	$60,000	a	year	for	promising	researchers	working	with	a		
mentor	on	a	key	issue	in	pediatric	medicine.	These	Fellowships	may	be		
renewed	for	up	to	three	years.


Educational Initiatives: $20,000
Are	awards	of	up	to	$10,000	for	specific	educational	activities,	such	as	the		
development	of	a	special	workshop	dealing	with	a	children’s	health	issue.




Grants Awarded
February, 2007 through July, 2009
Note: Results for grants that ended after January 31, 2009 will appear in the Report to Investors 2010.

Awards have been identified by color, please note chart below.




         Congenital Heart Disease Center




         McDonnell Pediatric Cancer Center




         Center for Pediatric Pulmonary Disease




         Center for Musculoskeletal and Metabolic Diseases




        CHILDREN’S	DISCOVERY	INSTITUTE		|		REPORT	TO	INVESTORS	2009
Grants Awarded                              Interdisciplinary Research Initiatives

2007

       Allan Doctor, MD – Pediatrics
       Loss of Vascular Control in Pediatric Lung Injury
       $200,000 (2/1/07 – 8/31/09)


       Justin Fay, PhD – Genetics
       The Comparative Genomics of Childbirth
       $200,000 (2/1/07 – 1/31/09) Completed Grant

         Identification of genes that cause pre-term birth could improve diagnosis and prevention of pre-term labor. Dr. Fay
         used a comparative genomics screen to identify 162 rapidly evolving genes and tested them for association with
         cases of pre-term birth. While no statistically significant associations were uncovered, the rapidly evolving genes
         identified can be further explored for potential linkages to other health issues.


       Ashley Hill, MD – Pathology & Immunology, and Christina A. Gurnett, MD, PhD – Neurology and Pediatrics
       Genetic Basis of the Pleuropulmonary Blastoma Family Cancer Syndrome
       $200,000 (2/1/07 – 7/31/09)


       Robi D. Mitra, PhD – Genetics
       Using Polony Sequencing to Detect p53 Hypermutability in Pediatric Gliomas
       (Technology to identify rare, inherited mutations in pediatric brain cancer.)
       $200,000 (2/1/07 – 1/31/09)

         During the course of this project, Dr. Robi Mitra and Dr. Todd Druley designed and validated a new method to comprehensively
         screen a common pool of DNA from over 1,000 individuals for rare inherited mutations. Their work was published in Nature
         Methods in March 2009. Their analysis also provided the first experimental evidence demonstrating that the cancer-causing gene,
         p53, is mutated more frequently than the rest of human genome in human cancers. This project has now moved to the Center for
         Pediatric Pulmonary Disease with a renewed grant.


       Kelle H. Moley, MD – Obstetrics and Gynecology
       Fetal Origins of Metabolic Syndrome and Cardiovascular Risk
       $200,000 (2/1/07 – 1/31/09) Completed Grant

         Using mouse models, Dr. Moley demonstrated that high fat intake by mothers before
         and during pregnancy may cause not only immediate effects on the fetus and neonate
         (low birth weight), but long lasting effects as well -- obesity, hypertension and diabetes
         during childhood and beyond. Future studies will assess whether these outcomes can
         be reversed. Dr. Moley has used these findings to apply for a NIH RC-1 grant.
         Her work was published in Endocrinology (2008), and Reproductive Sciences
         (2008 and 2009).




                                                                                                                      Collaborators Jean Shaffer, MD,
                                                                                                                           and Kelle Moley, MD




                                                                          Jeff Bednarski, MD, PhD




                                                                                                                                           	
                                                                                                    childrensdiscovery.org		|		314.286.0988	            9
Grants Awarded                                   Interdisciplinary Research Initiatives


     Thomas Morgan, MD – Pediatrics
     Consanguinity Mapping of Genes for Congenital Heart Disease
     $200,000 (2/1/07 – 6/30/08) Completed Grant

        Using powerful new microarrays capable of analyzing more than a million genetic markers per patient, Dr. Morgan
        and his colleagues studied 50 families in India in an effort to identify genetic linkages with congenital heart disease.
        Because first cousin or uncle-niece marriages are common in India, the power to detect genetic linkage between a
        gene and a disease trait is markedly increased by using such families. To date, chromosomes 21 and 22 have been
        fully analyzed and excluded for significant linkage to congenital heart disease. Dr. Morgan, now a member of the
        Center for Human Genetics Research at Vanderbilt University, is continuing this work under other funding.


     Karen L. Wooley, PhD – Chemistry
     Hyperbranched Fluoropolymers Designed as Complex Nanostructures for Imaging and Therapeutic
     Delivery in Diagnosis and Treatment of Pediatric Brain Cancers (Developing nanoparticles for use
     in chemotherapy.)
     $200,000 (2/1/07 – 1/31/09) Completed Grant

        Dr. Wooley and collaborators have made significant advances in the research of brain cancers
        in children using nanoscale objects as devices for targeted imaging and therapeutic delivery.
        They developed three nanostructures capable of packaging and releasing a chemotherapeutic agent.
        They also developed the ability for these nanostructures to bind to targeted tumor tissues both in vitro
        and in vivo (mouse models).


     Lijuan Zhang, PhD – Pathology & Immunology
                                                                                                                              nanostructure illustration
     Proteoglycan Regulation of Bone Growth and Development
     $200,000 (2/1/07 – 1/31/09) Completed Grant

        Dr. Zhang is part of a collaboration of Discovery Institute investigators working to understand bone growth disorders. Her research
        centered on understanding how specialized cells of the growth plate coordinate gene expression that impacts long
        bone development. Her results point to the possibility of using carbohydrate-based therapeutics to modulate growth
        plate function.




0   CHILDREN’S	DISCOVERY	INSTITUTE		|		REPORT	TO	INVESTORS	2009
Grants Awarded                               Interdisciplinary Research Initiatives
2008

        Barak A. Cohen, PhD – Genetics
        Genetic Analysis of Human Variation in B-Cell Activation
        $200,000 (2/1/08 – 1/31/10)


        Thomas W. Ferkol, MD – Pediatrics
        Gene Discovery and Treatment of Primary Ciliary Dyskinesia
        $200,000 (2/1/08 – 1/31/10)


        Anthony R. French, MD, PhD – Pediatrics
        Detecting Natural Killer Cell Functional Defects in Pediatric Patients with Recurrent Herpesvirus Infections
        $200,000 (2/1/08 – 1/31/10)


        Erik D. Herzog, PhD – Biology
        Cancer Chronotherapy: Circadian Rhythms and Tumor Biology
        $200,000 (2/1/08 – 1/31/10)


        Robert O. Heuckeroth, MD, PhD – Pediatrics
        Pharmacological and Nutritional Risk for Neural Crest Disorders
        $200,000 (2/1/08 – 1/31/10)


        Patrick Jay, MD, PhD – Pediatrics
        Insulin Resistance and Myocardial Glucose Metabolism in Pediatric Heart Failure
        $300,000 (2/1/08 – 1/31/11)


        Fanxin Long, PhD – Internal Medicine
        Mechanism for SHOX Proteins to Regulate Skeletal Growth
        $200,000 (2/1/08 – 1/31/10)


        William D. Smart, PhD – Computer Science and Engineering
        Control of a Robotic Hand Prosthesis Using Cortical Signals
        $200,000 (2/1/08 – 1/31/10)


2009	

        Ana Maria Arbelaez, MD – Pediatrics
        Neuronal Activation in Exercise-Induced Hypoglycemia Associated Autonomic Failure
        (A study to understand the relationship between exercise and hypoglycemia in diabetes.)
        $200,000 (2/1/09 – 1/31/11)


        Yehuda Ben-Shahar, PhD – Biology
        The Role of Divalent Metal Cation Homeostasis in Obesity
        $300,000 (2/1/09 – 1/31/12)


        Roberta Faccio, PhD – Orthopedic Surgery
        Novel Integrin/PLCgamma2/NF-kB Pathway in Neutrophils During Arthritis
        $200,000 (2/1/09 – 1/31/11)


        Sanjay Jain, MD, PhD – Medicine
        Mechanisms and Genetics of Congenital Urogenital Anomalies
        $300,000 (2/1/09 – 1/31/12)


        Robi D. Mitra, PhD – Genetics
        Rare Mutations Associated with Respiratory Distress in Infants
        $450,000 (2/1/09 – 1/31/12)




                                                                                                                                          	
                                                                                                   childrensdiscovery.org		|		314.286.0988	   
Grants Awarded                                     Interdisciplinary Research Initiatives



                                                                                     Nguyet Nguyen, MD
2009

       Nguyet Nguyen, MD – Medicine
       The Role of Lutheran/BCAM in Lung Development and Injury
       $200,000 (2/1/09 – 1/31/11)


       Joshua Rubin, MD, PhD – Pediatrics
       Characterization of the Brain Tumor Microenvironment Proteome
       $300,000 (2/1/09 – 1/31/11)


       Scott Saunders, MD, PhD – Pediatrics
       Heparan Sulfate: Simultaneous Modulators of Both Synergistic and Antagonistic Growth Factor Signaling in Bone Development
       $450,000 (2/1/09 – 1/31/12)


       David Wang, PhD – Molecular Microbiology
       Comprehensive Respiratory Virus Discovery and Detection in Pediatric Transplant Patients
       $300,000 (2/1/09 – 1/31/12)


       Barbara Warner, MD – Pediatrics
       The St. Louis Neonatal Gut Microbiome Initiative
       $450,000 (2/1/09 – 1/31/12)


       Monita Wilson, PhD – Medicine
       A Mouse Model Linking Aberrant Inositol Cycling to Neural Tube Defects
       $300,000 (2/1/09 – 1/31/12)


       Dong Yu, PhD – Molecular Microbiology
       Endothelial and Epithelial Tropism of Human
       Cytomegalovirus (Understanding how
       this virus that causes birth defects
       and is a complication in
       children receiving transplants
       can target certain cells.)
       $200,000
       (2/1/09 – 1/31/11)




                                                                                                                              Josh Rubin, MD, PhD




2     CHILDREN’S	DISCOVERY	INSTITUTE		|		REPORT	TO	INVESTORS	2009
Grants Awarded                             Fellowships


2007

       Todd E. Druley, MD, PhD – Pediatrics
       Genomic Analysis of p53 Hypermutability in High-Grade Pediatric Astrocytoma
       (Using new sequencing methods to uncover rare mutations in pediatric brain cancers.)
       $40,000 (2/1/07 – 1/31/10)


       Amir Toib, MD – Pediatrics
       Normal and Abnormal Embryonic Development of the Heart’s Ventricular Septum
       $30,000 (7/1/07 – 6/30/10)




2008

       Rajalaxmi Natarajan, PhD – Genetics
       Identifying Interactors of Sanpodo Essential for Notch-Mediated Assymetric Division in the Nervous System
       (Elucidating specific pathways in nervous system development.)
       $40,000 (2/1/07 – 1/31/09) Completed Grant

         Dr. Natarajan’s investigation has added knowledge to the role of asymmetric cell division in cancer.
         Asymmetric cell division is the process by which a cell divides to give rise to daughter cells that exhibit
         distinct developmental destinies from their time of birth. In her research, she has uncovered a previously
         unknown role for the tumor suppressor, p53 in the normal development of the nervous system.


       Ali Nekouzadeh, PhD – Biomedical Engineering
       The Molecular Mechanism of Genetically Inherited Cardiac Arrhythmia
       $40,000 (2/1/08 – 1/31/10)




2009

       Jeff Bednarski, MD, PhD – Pediatrics
       Regulation of Transcriptional Responses to DNA Damage
       $60,000 (2/1/09 – 1/31/11)


       Stephen Rogers, PhD – Pediatrics
       Regulation of Antioxidant Defense in Red Blood Cells by Oxygen and Nitric Oxide
       (Studying ways to avoid lung injury in children with severe inflammation.)
       $60,000 (2/1/09 – 1/31/11)




                                                                                                                                          	
                                                                                                   childrensdiscovery.org		|		314.286.0988	   3
 Grants Awarded                                         Faculty Scholar Awards



            Christina A. Gurnett, MD, PhD, Faculty Scholar – Neurology and Pediatrics,
            received a B.S. in Biology from the University of Notre Dame in 1991 and her M.D. and Ph.D.
            degrees from the University of Iowa in 1998, where she also completed a two-year residency
            in pediatrics. In 2000, she came to Washington University for training in Adult and Pediatric
            Neurology, and in 2004, completed a fellowship in Pediatric Epilepsy at the St. Louis Children’s
            Hospital Pediatric Epilepsy Center. Dr. Gurnett started her own laboratory in 2007 to focus
     2007




            on the genetic basis of musculoskeletal and neurological disorders. In 2008, Dr. Gurnett’s
            laboratory identified a genetic cause of clubfoot in a large family with inherited lower limb
            abnormalities. $200,000 (2/1/07 – 1/31/10)




            Robert H. Baloh, MD, PhD, Faculty Scholar – Neurology, received his Sc.B. with
            honors in Neuroscience from Brown University in 1995, and his M.D./Ph.D. from Washington
            University in 2001. He then did his medical internship at Brigham and Women’s Hospital in
            Boston, and his neurology residency at the Massachusetts General Hospital/Brigham and
            Women’s Hospital combined neurology program, where he served as Chief Resident in his
            final year. He completed a fellowship in neuromuscular diseases at Washington University
     2008




            in 2006 before joining the Washington University School of Medicine faculty as Assistant
            Professor of Neurology. His laboratory is focused on understanding the mechanisms of Genetic
            Neuromuscular Disease. $250,000 (2/1/08 – 1/31/10)




            Jennifer G. Duncan, MD, Faculty Scholar – Pediatrics, completed a B.S. in molecular
            biology at Vanderbilt University in 1993, and her medical degree at The University of Chicago
            Pritzker School of Medicine in 1997. Following a pediatric residency at The University of
            Chicago Children’s Hospital, she completed a pediatric critical care fellowship at Johns Hopkins
            University. Dr. Duncan joined the faculty at Washington University School of Medicine in 2004,
            and is Assistant Professor of Pediatrics. Her laboratory studies how alterations in the environment
     2008




            of developing organisms may reprogram mitochondria and predispose to risk of disease later in
            life. $250,000 (2/1/08 – 1/31/10)




            Audrey Odom, MD, PhD, Faculty Scholar – Pediatrics, received her B.S. and Ph.D
            degrees from Duke University in 1996 and 2002, and completed her M.D. in 2003 from
            Duke University School of Medicine. Before coming to Washington University in July of 2008
            as instructor of pediatrics, Dr. Odom did a pediatric residency and a fellowship in pediatric
            infectious diseases at the University of Washington. Her laboratory studies the protozoan
            parasite Plasmodium Falciparum, the causative agent of severe malaria, responsible for over
     2009




            a million child deaths a year.$300,000 (2/1/09 – 1/31/12)




4          CHILDREN’S	DISCOVERY	INSTITUTE		|		REPORT	TO	INVESTORS	2009
Grants Awarded                              Large Initiatives


                                                                                      Stephen Brody, MD, and Jian Xu, MD
2007

       Steven L. Brody, MD – Medicine
       Airway Epithelial Cell Core
       (Providing specialized cultured lung cells for research.)
       $350,000 (4/15/07 – 4/14/10)


       Robert O. Heuckeroth, MD, PhD – Pediatrics
       Structural Chromosomal Variants in Children with Congenital Anomalies
       $1,125,000 (4/15/07 – 4/14/10)


       Jeff Leonard, MD – Neurosurgery
       The Brain TumorBank
       $350,000 (7/1/07 – 6/30/09)


       Joshua Rubin, MD, PhD – Pediatrics
       Identifying a Clinically Available PDE4 Inhibitor for Treatment of Children
       with Malignant Brain Tumors
       $50,000 (7/1/08 – 6/30/09)


       Sheila A. Stewart, PhD – Cell Biology & Physiology
       Enabling Applied Genomic Technologies in Pediatrics
       (Providing novel technology that allows the selective manipulation of gene
       expression in human cancer cells derived directly from children with
       pediatric brain tumors.)
       $600,000 (7/1/07 – 5/30/09)




                                                                    Sheila Stewart, PhD




                                                                                                                                                	
                                                                                                         childrensdiscovery.org		|		314.286.0988	   5
 Grants Awarded                                     Large Initiatives

                                                                                                 Thomas Ferkol, MD
 2008

        Thomas W. Ferkol, MD – Pediatrics
        Functional, Structural, and Genetic Characterization of Pediatric Ciliopathies
        $600,000 (7/1/08 – 6/30/11)


        Reid Townsend, MD – Internal Medicine
        An Advanced Mass Spectrometric Platform for Comparative Clinical Proteomics
        (This award partially supports instruments used by Institute investigators to
        analyze and characterize proteins.)
        $150,000 (7/1/08 – 6/30/10)




 2009

        Todd Druley, MD, PhD – Pediatrics, and Robi Mitra, PhD – Genetics
        Accelerating Novel Genetic Discoveries via Next-generation DNA Sequencing
        $1,100,000 (7/1/09 – 6/30/12) *Resources are equally shared by all Centers


        David Ornitz, MD, PhD – Developmental Biology
        Sperm Cryopreservation and Intracytoplasmic Sperm Injection Technology Initiative
        (Reduces cost of maintaining mouse models used by Institute investigators.)
        $450,000 (7/1/09 – 6/30/12) *Resources are equally shared by all Centers


        George Van Hare, MD – Pediatrics
        Electrocardiographic Imaging in Congenital Heart Disease Following Repair
        $200,000 (7/1/09 – 6/30/12)


        Jeff Leonard, MD – Neurosurgery
        Pediatric Brain Tumor Bank
        $700,000 (7/1/09 – 6/30/12)




 Grants Awarded                                     Educational Initiatives
 2007

        Tyler E. Reimschisel, MD – Pediatrics, Neurology, Genetics
        Educational Program for Pediatric Residents at St. Louis Children’s Hospital
        $10,000 (2/1/07 – 1/31/08) Completed Grant

           During 2007 and 2008, pediatric medical residents received a comprehensive review of genetic and genomic medicine via six
           one-hour case-based discussions. Actual cases of congenital heart disorders provided the context to teach concepts of genetics
           and genomic medicine. The understanding gained by the residents will improve the clinical care provided to children with
           congenital heart disease and other genetic conditions.


        Matthew B. Dobbs, MD – Orthopedic Surgery
        The Genetic Basis of Musculoskeletal Birth Defects Symposium
        (This symposium was held June 19, 2009.)
        $10,000 (2/1/07 – 7/1/09)


        Kathryn G. Miller, PhD – Biology
        Undergraduate Summer Research in Pediatric Diseases
        $75,000 (4/15/07 – 4/14/10)




6      CHILDREN’S	DISCOVERY	INSTITUTE		|		REPORT	TO	INVESTORS	2009
Children’s Discovery Institute Leadership
Executive Director                                                         Board of Managers
Alan L. Schwartz, MD, PhD		                                                Senior	business	executives,	investors	and	leaders	in	medicine	and	
  H
	 	 arriet	B.	Spoehrer	Professor	and	Chairman	of	the	Department	of	        research	at	St.	Louis	Children’s	Hospital,	Washington	University,	the	
  Pediatrics	at	Washington	University	School	of	Medicine;	Professor	       local	community,	and	beyond	provide	oversight	to	the	Discovery	
  of	Developmental	Biology;	Pediatrician	In-Chief,	St.	Louis	              Institute.	This	board	approves	proposed	allocation	of	funds.
  Children’s	Hospital
                                                                           Members:
Scientific Advisory Board                                                  Roger N. Beachy, PhD		
Internationally	recognized	science	leaders	oversee	research	initiatives	     P
                                                                           	 	 resident,	Donald	Danforth	Plant	Science	Center
and	direction	through	review	and	recommendation	of	grant	awards
                                                                           Dale L. Cammon		
Members:                                                                     P
                                                                           	 	 resident,	Bryant	Group,	Inc.	
Susan K. Dutcher, PhD		
  P
	 	 rofessor	and	Head,	Department	of	Genetics,		                           Arnold W. Donald		
  Washington	University	School	of	Medicine                                   R
                                                                           	 	 etired	President	and	CEO,	Juvenile	Diabetes	Research		
                                                                             Foundation	International
Robert P. Mecham, PhD		
  A
	 	 lumni	Endowed	Professor	of	Cell	Biology,	Department	of		               Thomas E. Ellenberger, DVM, PhD		
  Cell	Biology	&	Physiology,	Professor	of	Medicine	and	Professor		           H
                                                                           	 	 ead	of	Department	of	Biochemistry	&	Molecular	Biophysics,	
  of	Pediatrics,	Washington	University	School	of	Medicine                    Wittcoff	Professor,	Washington	University	School	of	Medicine	

Barbara A. Schaal, PhD		                                                   Lee F. Fetter (Ex-officio)		
  M
	 	 ary-Dell	Chilton	Distinguished	Professor	in	Arts	&	Sciences,	            P
                                                                           	 	 resident,	St.	Louis	Children’s	Hospital	and	Group	President,		
  Washington	University;	Vice	President	of	the	U.S.	National	                BJC	HealthCare
  Academy	of	Sciences
                                                                           Richard H. Gelberman, MD		
Steven L. Teitelbaum, MD		                                                    H
                                                                           	 	 ead	of	Department	of	Orthopedic	Surgery,	Reynolds	Professor,	
   W
	 	 ilma	and	Roswell	Messing	Professor	of	Pathology,		                        Washington	University	School	of	Medicine
   Department	of	Pathology	&	Immunology,	Washington		
   University	School	of	Medicine                                           Keith S. Harbison		
                                                                             P
                                                                           	 	 resident	and	Chief	Executive	Officer,	Harbison	Corporation	
Michael J. Welsh, MD		
  R
	 	 oy	J.	Carver	Professor	of	Medicine	and	Cell	Biology	and	               Richard J. Mahoney		
  Investigator,	Howard	Hughes	Medical	Institute,	Roy	J.	and		                 R
                                                                           	 	 etired	Chairman	&	CEO,	Monsanto	Company,	Distinguished	
  Lucille	A.	Carver	College	of	Medicine,	University	of	Iowa                   Executive	in	Residence	at	the	Murray	Weidenbaum	Center	on		
                                                                              the	Economy,	Government	and	Public	Policy,	Washington	
Huda Y. Zoghbi, MD		                                                          University	in	St.	Louis
  P
	 	 rofessor	of	Pediatrics,	Molecular	and	Human	Genetics,		
  Neurology	and	Neuroscience	and	Investigator,	Howard	Hughes	              James S. McDonnell III		
  Medical	Institute,	Baylor	College	of	Medicine                              R
                                                                           	 	 etired	Corporate	Vice	President,	McDonnell	Douglas	Corp.

                                                                           Charles W. Mueller (Board Chair)		
                                                                           	 Retired	Chairman	&	CEO,	Ameren	Corporation

                                                                           William B. Neaves, PhD		
                                                                           	 President	&	CEO,	Stowers	Institute	for	Medical	Research	

                                                                           Alan L. Schwartz, MD,	PhD 	
                                                                             H
                                                                           	 	 ead	of	Department	of	Pediatrics,	St.	Louis	Children’s	Hospital	
                                                                             Harriet	B.	Spoehrer	Professor	of	Pediatrics,	Washington	University	
                                                                             School	of	Medicine

                                                                           Larry J. Shapiro, MD (Ex-officio)		
                                                                             E
                                                                           	 	 xecutive	Vice	Chancellor	for	Medical	Affairs	and	Dean	
                                                                             Washington	University	School	of	Medicine

                                                                           Raymond R. Van de Riet, Jr.		
                                                                           	 Managing	Director,	LEAR	Capital	LLC
                                                                                                                                    PRSRT STD
                                                                                                                               U.S. POSTAGE PAID
                                                                                                                                 ST. LOUIS, MO
                                                                                                                                PERMIT NO. 1291




St. Louis Children’s Hospital Foundation
One	Children’s	Place,	St.	Louis,	MO	63110




      Second Annual Children’s Discovery Institute
      Investor Symposium is September 30, 2009.
                                            Meet	Children’s	Discovery	Institute	Investigators.	Learn	about	their	exciting	research	
                                            via	posters	and	short,	“comprehendible-by-non-scientists”	presentations.	Hear	about	
                                            results	achieved,	future	plans	and	the	inner-workings	of	the	Institute	from	its	leaders.


                                            The	symposium	will	begin	at	6:30	p.m.	on	Wednesday, September 30,	2009
                                            at	the	Eric P. Newman Education Center at 320 S. Euclid Avenue	(next	to	
                                            St.	Louis	Children’s	Hospital	and	the	McDonnell	Pediatric	Research	Building).	


                                            Valet parking will be provided.


                                            For	more	information	or	to	RSVP,	please	call	Rebecca	Bergson	at	314.286.1553.