Emphasis Program

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					                              Emphasis Program
              Potential Mentors/Project Possibilities
                     Laboratory-Based Biomedical Research


Potential Mentor's Info.                    Additional Contact Info.

Sarki Abdulkadir
sarki.a.abdulkadir@vanderbilt.edu
(615)322-9668

Project Title: [No title given]
Project Synopsis: Tumorigenesis is intimately associated with alterations in the
dosage of individual genes and whole genomes. At the genome level, polyploidization,
a process in which cells acquire more than two sets of homologous chromosomes, is
common in tumors and is a cornerstone of a long-standing hypothesis of tumorigenesis
first proposed by Theodore Boveri almost a century ago. However, because cancer
cells have unstable genomes, whether polyploidy is a cause rather than a consequence
of tumorigenesis has remained a vexing question in cancer research. At the single gene
level, alterations in copy number (gains or losses) are common mechanisms for the
activation or inactivation of cancer genes. Contrary to the classical two-hit hypothesis
of tumor suppressor gene (TSG) inactivation, some tumor suppressor genes
demonstrate haploinsufficiency, where one allele is unable to sustain normal cellular
function. We are exploring the mechanisms and functional consequences of polyploidy
and TSG haploinsufficiency in tumorigenesis. Studies are focused on exploring the
mechanisms of polyploidy-induced tumorigenicity and on defining the effects of
polyploidy on chromosomal stability, mutations and gene regulation. Our model of
haploinsufficient tumor suppression is based on deletion of the prostate tumor
suppressor Nkx3.1 in mice. Current efforts are aimed at exploring the mechanisms
involved, including the role of chromatin context in determining dosage-sensitivity.

Potential Mentor's Info.                    Additional Contact Info.

Thomas Andl
thomas.andl@vanderbilt.edu
6153221716

Project Title: [No title given]
Project Synopsis: The skin is the organ that most obviously demonstrates the effects
of aging on the human body. This research project will analyze the changes and the
biological significance of a new class of genes, microRNA genes, in the aging process.
The overseeable number of microRNAs makes it easier to characterize and compare
specific states of a tissue. This approach has proven very helpful in the definition of
tumors and will allow a clearer molecular definition of aging. The project involves the
analysis of skin tissue samples and cell cultures of keratinocytes and fibroblasts, the
measurement of microRNA expression and the the comparison of the length of the
3'untranslated regions of mRNA (the major target of microRNA function) in young,
old and tumorigenic skin cells.

Potential Mentor's Info.                     Additional Contact Info.

Claudia Andl
claudia.andl@vanderbilt.edu
615-322-0376

Project Title: [No title given]
Project Synopsis: Patients suffering from esophageal cancer generally present with
advanced disease resulting in a high mortality rate. More than 50% of the patients have
metastatic progression at the time of presentation. The main focus of my research is on
cell signaling events leading to increased cell migration and invasion. We previously
reported that 70% of espohageal tumors exhibit coordinated loss of Ecadherin (Ecad)
and TGFβ receptor II (TGFRII). Therefore, various projects in the lab concern the
analysis of primary esophageal cenns expressing mutants of Ecad and TGFRII. The
interaction of these molecules appears to be important in regulating protein stability as
well as cell signaling. I also established an in vitro system to model cell invasion in a
organotypic reconstruct in which the newly formed epithelium grows on a matrix
consisting of fibroblasts embedded in matrigel/collagen. This systems allows to
investigate and modulate the cross-talk with the tumor microenvironment.
Downstream targets of Ecad and TGFRII loss are involved in cell invasion as well as
cell signaling, some of which we recently discovered through RNA microarray and are
planning to exploit for potential diagnostic and/or therapeutic approaches.

Potential Mentor's Info.                     Additional Contact Info.
                                             Claudia Andl
Claudia Andl
                                             claudia.andl@vanderbilt.edu
claudia.andl@vanderbilt.edu
                                             615.343.8401
615-322-0376
                                             1161 21 Ave S, MCN D2300
Project Title: [No title given]
Project Synopsis: Patients suffering from esophageal cancer generally present with
advanced disease resulting in a high mortality rate. More than 50% of the patients have
metastatic progression at the time of presentation. The main focus of my research is on
cell signaling events leading to increased cell migration and invasion. I previously
reported that 70% of espohageal tumors exhibit coordinated loss of Ecadherin (Ecad)
and TGFβ receptor II (TGFRII). Therefore, various projects in the lab concern the
analysis of primary esophageal cells expressing mutants of Ecad and TGFRII. The
interaction of these molecules appears to be important in regulating protein stability as
well as cell signaling. I also established an in vitro system to model cell invasion in a
organotypic reconstruct in which the newly formed epithelium grows on a matrix
consisting of fibroblasts embedded in matrigel /collagen. This systems allows to
investigate and modulate the cross-talk with the tumor microenvironment.
Downstream targets of Ecad and TGFRII loss are involved in cell invasion as well as
cell signaling, some of which we recently discovered through RNA microarray and are
planning to exploit for potential diagnostic and/or therapeutic approaches.

Potential Mentor's Info.                     Additional Contact Info.

Jennifer Blackford
Jennifer.Blackford@Vanderbilt.edu
343-0715

Project Title: [No title given]
Project Synopsis: Temperament refers to the individual differences in emotions,
cognitions and behaviors based on biology that are first observed in infancy or early
childhood. Temperament is important because of its role in both normative
development and psychopathology. These early temperamental differences in infants
are sculpted by environments into adult personality traits. Temperamental factors have
also been implicated in the development of psychiatric disorders such as anxiety,
depression, ADHD, and substance abuse. Brain imaging methods such as fMRI
provide new opportunities to discover the neural basis of differences in temperament,
which may provide unique insights into psychiatric illnesses. The amygdala has been
proposed as a key brain structure for both inhibited temperament (predisposition to
avoid novel people, places and things) and anxiety and depression. The amygdala
typically shows a response to novelty that habituates with repeated exposure. Slower
habituation may be a hallmark feature of risk for anxiety. In this project, you would
compare rates of amygdala habituation to human faces in people with inhibited versus
uninhibited temperament using an existing fMRI dataset.

Potential Mentor's Info.                     Additional Contact Info.

Dorin Borza
Dorin-Bogdan.Borza@vanderbilt.edu
615-322-4470

Project Title: [No title given]
Project Synopsis: Research in Borza lab is focused on the role of type IV collagen
networks in health and disease. The alpha3/4/5(IV) collagen network is a major
component of the glomerular basement membrane (GBM), centrally implicated in the
pathogenesis of various forms of hereditary nephritis (Alport syndrome, thin GBM
disease), as well as antibody-mediated glomerulonephritis (autoimmune and
alloimmune forms of anti-GBM disease, Goodpasture disease). Our lab studies the
molecular mechanisms by which immune tolerance to type IV collagen chains is
normally established in health, broken in autoimmune anti-GBM/Goodpasture disease,
or selectively deficient in alloimmune Alport post-transplant nephritis. Using mouse
models (including wild type and antigen-knockout mice, or transgenic mice expressing
human autoantigen), we investigate how the abnormal engagement of cellular and
humoral adaptive immune responses against alpha3/4/5(IV) collagen lead to the
production of nephritogenic auto-antibodies and allo-antibodies. Studies in animal
models are instrumental for understanding the molecular mechanisms underlying the
pathogenesis of these human diseases.

Potential Mentor's Info.                      Additional Contact Info.

Stephen Brandt
stephen.brandt@vanderbilt.edu
615-936-1809

Project Title: [No title given]
Project Synopsis: Potential projects are available in the laboratory that relate to
transcriptional regulation and normal and leukemic hematopoiesis and in the clinic that
relate to hematopoietic stem cell transplantation.

Potential Mentor's Info.                      Additional Contact Info.

David Calkins
david.j.calkins@vanderbilt.edu
(615) 936-6412

Project Title: [No title given]
Project Synopsis: Parallel projects are available to emphasis students that utilize
cellular, molecular and pharmacological tools to study mechanisms of
neurodegeneration in glaucoma. In particular, the laboratory focuses on the earliest
molecular events that result in the degeneration of retinal ganglion cells and their
axons, which comprise the optic nerve. A particular effort is underway to discern the
contribution of calcium channels to loss of axonal transport in response to changes in
ocular pressure. The actions of these channels are often countered by neuroprotective
signals arising from glial cells in the retina and optic nerve. Projects are also available
to identify these signals, characterize their intracellular pathways, and understand how
they modulate neuronal survival in glaucoma.

Potential Mentor's Info.                      Additional Contact Info.

David Calkins
david.j.calkins@vanderbilt.edu
(615) 936-6412

Project Title: [No title given]
Project Synopsis: Glaucoma affects some 80 million people worldwide and blinds
through the degeneration of retinal neurons and their axons in the optic nerve. It is the
primary cause of irreversible vision loss worldwide. Our neuroscience laboratory
focuses on the cellular and molecular cascades that initiate neurodegeneration in
glaucoma and on testing whether those cascades could be relevant targets for novel
therapeutic interventions. Early neurodegenerative events in glaucoma include axonal
transport deficits, synaptic pruning, calcium dysregulation, and a host of susceptibility
factors that influence neuronal survival. An important question is the extracellular
signals between neurons, glia and vascular elements that modulate the degenerative
cascade. An Emphasis project will include using both in vitro and in vivo models to
isolate these extracellular signals and determine their influence on the system-wide
response in glaucoma. Tools include quantitative PCR, cell culture, rodent models,
immuno- and genetic labeling, and confocal and electron microscope.

Potential Mentor's Info.                     Additional Contact Info.

Bruce Carter
bruce.carter@vanderbilt.edu
(615) 936-3041

Project Title: [No title given]
Project Synopsis: This project involves studying the molecular mechanisms
underlying the formation of peripheral myelin. In particular, how axonal signals result
in Schwann cell precursors differentiating into a myelinating phenotype. This study
has relevance not only for normal development, but also for diseases like Charcot-
Marie Tooth, one of the most common muscular dystrophies.

Potential Mentor's Info.                     Additional Contact Info.

Bruce Carter
bruce.carter@vanderbilt.edu
(615) 936-3041

Project Title: [No title given]
Project Synopsis: This research project will investigated the mechanisms of neuronal
apoptosis mediated through the p75 neurotrophin receptor, which is involved in
neuronal loss during normal development as well as after various injuries and diseases.

Potential Mentor's Info.                     Additional Contact Info.

Carissa Cascio
carissa.cascio@vanderbilt.edu
(615) 936-3598

Project Title: [No title given]
Project Synopsis: In collaboration with other researchers, my lab uses a combination
of behavioral sensory tests and neuroimaging to look at sensory processing problems
in people with autism. I'm interested in how these sensory problems may be related to
motivation, affect, and repetitive behaviors, which are all affected by autism.

Potential Mentor's Info.                     Additional Contact Info.

David Cortez
david.cortez@vanderbilt.edu
615-322-8547

Project Title: [No title given]
Project Synopsis: The Cortez lab is dedicated to understanding the cellular process
that regulate genome integrity. Defects in these process cause diseases including
cancer, neurodegenerative disorders, and premature ageing. Biochemical, genetic and
cell biological methods in mammalian and yeast systems are combined in a
multidisciplinary approach. The lab is part of the Vanderbilt-Ingram Cancer Center,
Center in Molecular Toxicology, Vanderbilt Institute of Chemical Biology, and
Department of Biochemistry. Projects using molecular biology, RNA interference, and
human cell culture are available for students.

Potential Mentor's Info.                     Additional Contact Info.

Clarence Creech
clarence.b.creech@vanderbilt.edu
6153430332

Project Title: [No title given]
Project Synopsis: In this study, we will be assessing nasal, throat, and skin
colonization with S. aureus and MRSA in a cohort of over 200 men and women
participating in varsity athletic programs at Vanderbilt University. In addition, we will
seek to link colonization strains with disease-causing strains in the laboratory.

Potential Mentor's Info.                     Additional Contact Info.

Clarence Creech
clarence.b.creech@vanderbilt.edu
6153430332

Project Title: [No title given]
Project Synopsis: Ongoing projects in our group include: 1) assessment of staph
colonization in mothers and newborns (closing soon) 2) assessment of staph
colonization in university athletes 3) frequency of PICC line complications in children
4) epidemiology of bone and joint infections in children 5) molecular epidemiology of
S. aureus infections in a variety of settings: surgical intensive care, pediatrics 6)
epidemiology of S. aureus in other regions - Costa Rica (ongoing with MSCI student)
and Argentina (just starting to develop protocols)

Potential Mentor's Info.                    Additional Contact Info.
                                            Patsy Mason
James Crowe
                                            patsy.mason@vanderbilt.edu
james.crowe@vanderbilt.edu
                                            615-343-8064
615-343-8064
                                            T-2220 MCN
Project Title: [No title given]
Project Synopsis: We conduct detailed laboratory studies of the molecular and
cellular basis for immunology and cell biology of virus infection. Applicants are best
off if they already have some previous laboratory experience.

Potential Mentor's Info.                    Additional Contact Info.

Richard D'Aquila
richard.daquila@Vanderbilt.Edu
615-322-8972

Project Title: [No title given]
Project Synopsis: Student may help design/adapt a specific project in area of HIV
pathogenesis and antiretroviral therapeutics to their own interests. The laboratory
studies antiretroviral drug resistance and cellular proteins important in HIV
pathogenesis during therapy. These cellular proteins include APOBEC3G (and related
proteins) that serve as intrinsic defenses against reverse transcription in lymphocytes.
There are also studies underway of lymphocyte drug transporters that modulate
intracellular concentrations of antiretroviral drugs.

Potential Mentor's Info.                    Additional Contact Info.

Sukdeb Datta                                Kim Suttle
sukdeb.datta@vanderbilt.edu                 kim.suttle@vanderbilt.edu
615-322-4311

Project Title: [No title given]
Project Synopsis: Several lines of evidence suggest Cholecystokinin (CCK) acting
through CCK-2 receptors in the dorsal horn contributes to neuropathic pain
Effectiveness of morphine as an analgesic in neuropathic pain is poor but enhanced by
CCK-2 antagonists suggesting that increased dorsal horn CCK and/or CCK-2 receptor
activity are/is involved in opioid resistance common to neuropathic states. Even
though potentiation of analgesia induced by exogenous administration of opioids in
combination with CCK antagonists has been investigated, only few studies have been
performed on the interactions between endogenous CCK and opioid systems. In
addition, better animal modeling of neuropathic pain is needed to accurately predict
therapeutic efficacy and elucidate pathobiology. Our behavior and anatomic data on a
bilateral chronic constriction injury (bCCI) model showed that CCK in the dorsal horn
was decreased at all time frames (30,60 and 90 days) when nociceptive responsiveness
to cold stimuli was increased . The decrease in CCK staining may reflect increased
release>synthesis or decreased synthesis by neurons in the DH. CCK and mu opiate
receptor co-localize in the SDH. We have also shown that a specific neuropeptide
toxin conjugate, intrathecal CCK –saporin has behavioral and anatomic consequences
in these two interactive systems. Specific objectives for this proposal include
determining the anatomic efficacy and selectivity of intrathecal CCK-saporin toward
dorsal horn neurons expressing CCK-2 receptor, the effects of optimal intrathecal
doses of CCK-saporin on innate reflex and operant nocifensive responses in normal
and neuropathic rats and the analgesic potency of morphine in normal and CCK-
saporin injected rats before and after bCCI and study of interactions between the CCK
and opioidergic systems. Clinical implications include possible new applications in
neuropathic pain, particularly if CCK-saporin if found to be anti-neuropathic or if it
potentiates opioid analgesia.

Potential Mentor's Info.                   Additional Contact Info.

Jerod Denton
jerod.s.denton@vanderbilt.edu
343-7385

Project Title: [No title given]
Project Synopsis: Kir1.1 K+ channels play key roles in regulation of fluid and
electrolyte balance by the kidney. The importance of Kir1.1 in renal function is
underscored by the identification of heritable mutations in the channel that cause
Bartter syndrome, a kidney disorder characterized by salt and water wasting and acid-
base disturbances. More than 40 disease-causing mutations in Kir1.1 have been
identified, however the molecular mechanisms underlying Kir1.1 dysfunction are
poorly understood. The Denton laboratory is using a combination of patch clamp
electrophysiology, molecular biology, protein biochemistry, molecular modeling and
fluorescence imaging techniques to build a comprehensive understanding of how
mutations in Kir1.1 result in channel dysfunction and disease.

Potential Mentor's Info.                   Additional Contact Info.

Wonder Drake
wonder.drake@vanderbilt.edu
322-1802

Project Title: [No title given]
Project Synopsis: Idiopathic lung disease represents one of disease that causes
significant morbidity among patients during their most productive years. Recent
molecular and immunologic studies support the presence of previously undescribed
microorganisms. Our current project involve investigation of immune recognition of
microbial antigens and concomitant analysis of pathologic specimens for microbes to
assess their role in idiopathic lung diseases such as sarcoidosis.

Potential Mentor's Info.                     Additional Contact Info.

Florent Elefteriou
florent.elefteriou@vanderbilt.edu
615-322-7975

Project Title: [No title given]
Project Synopsis: - Regulation of bone remodeling and bone mass by the central and
peripheral nervous system - Regulation of beta2-adrenergic signaling in osteoblasts -
Skeletal defect of neurofibromatosis - Stress and cancer bone metastasis Approaches:
Mutant mouse models, molecular biology, biochemistry, primary cell culture

Potential Mentor's Info.                     Additional Contact Info.

Maureen Gannon
maureen.gannon@Vanderbilt.Edu
615-936-2676

Project Title: [No title given]
Project Synopsis: We have recently discovered that connective tissue growth factor
(CTGF) is produced by pancreatic beta cells, pancreatic duct cells and pancreatic
blood vessels during embryonic development in the mouse. We have also shown that
CTGF is required during development for beta cell proliferation to generate the
appropriate number of insulin-producing cells at birth. The student will dissect the role
of CTGF during pancreas development using cultures of embryonic pancreas buds. In
addition, the student will use conditional gene knockout models to determine which
cellular source of CTGF during development is essential for normal beta cell
proliferation. Techniques include: microdissection, organ culture, histology,
immunohistochemistry, mouse husbandry, RT-PCR. These studies have implications
for the production and expansion of beta cells from stem cell sources or from cadaver
donors for use in the treatment of diabetes.

Potential Mentor's Info.                     Additional Contact Info.

Steven Goudy
steven.l.goudy@vanderbilt.edu


Project Title: [No title given]
Project Synopsis: The Notch signaling pathway plays a critical role during
development. Notch1 is a transmembrane receptor responsible for directing vascular
and epithelial development. In mice, Notch1 deficient embryos have severe cardiac
anomalies, but die before craniofacial development occurs. Other studies have shown
that reduction in Notch1 signaling leads to craniofacial defects as well. The role of
Notch1 signaling in craniofacial development has not been studied to date. Our lab
will perform targeted genetic deletion of Notch1 signaling in the epithelium and
mesenchyme of the face. We will then identify which craniofacial structures are
altered when Notch1 is absent. Furthermore, we will show which other signaling
molecules involved in Notch signaling are altered using in situ hybridization. The
epithelial and vascular development of these mice will be characterized using
immunohistochemistry. Future studies may involve determining gene-gene
interactions between Notch1 signaling and other candidate genes.

Potential Mentor's Info.                     Additional Contact Info.

Guoqiang Gu
guoqiang.gu@vanderbilt.edu
936-3634

Project Title: [No title given]
Project Synopsis: We utilized mouse and chicken embryos to study pancreatic
endocrine islet development. Projects include examining gene expression patterns,
investigate effect of ectopic gene expression, and examining the phenotype when
specific genes are knocked out in mouse.

Potential Mentor's Info.                     Additional Contact Info.

Vsevolod Gurevich
vsevolod.gurevich@vanderbilt.edu
(615) 322-7070

Project Title: [No title given]
Project Synopsis: My lab studies structure and function of arrestin proteins that are
involved in a variety of cell signaling pathways. We use a broad range of methods,
from biochemistry and biophysics to cell-based assays and transgenic mice. Potential
projects can include site-directed mutagenesis and in vitro functional assays, work
with purified proteins, receptor and arrestin functional studies in cell culture, or even
work with mice to study their visual system and participation in our attempts to correct
genetic deficiencies with "super-arrestin" mutants.

Potential Mentor's Info.                     Additional Contact Info.

Volker Haase
volker.haase@vanderbilt.edu
615-343-7254
Project Title: [No title given]
Project Synopsis: The Haase laboratory studies the VHL/HIF oxygen-sensing
pathway and uses conditional gene targeting technology and transgenesis, as well as
biochemical and functional genomics approaches to define the specific roles of the von
Hippel-Lindau (VHL) tumor suppressor and individual HIF transcription factors in
tumorigenesis, acute ischemia and chronic hypoxic injury, as well as erythropoiesis
and iron metabolism. Hypoxia-Inducible Factors HIF-1 and HIF-2 are oxygen-
sensitive basic helix-loop-helix transcription factors, which regulate biological
processes that facilitate both oxygen delivery and cellular adaptation to oxygen
deprivation. HIFs consist of an oxygen-sensitive alpha-subunit, HIF-alpha and a
constitutively expressed beta-subunit, HIF-beta, and regulate the expression of genes
that are involved in energy metabolism, angiogenesis, erythropoiesis and iron
metabolism, cell proliferation, apoptosis and other biological processes. Under
conditions of normal oxygen tension HIF-alpha is hydroxylated and targeted for rapid
proteasomal degradation by the von VHL/E3-ubiquitin ligase. When cells experience
hypoxia, HIF-alpha is stabilized and either dimerizes with HIF-beta in the nucleus to
form transcriptionally active HIF executing the canonical hypoxia response, or it
physically interacts with other non-HIF proteins, enabling convergence of HIF oxygen
sensing with other signaling pathways. Since HIF increases the expression of
cytoprotective factors and erythropoietin, pharmacologic inhibition of HIF-alpha
degradation offers enormous potential for the treatment of acute hypoxic injuries and
anemia.

Potential Mentor's Info.                     Additional Contact Info.

Dennis Hallahan
dennis.hallahan@vanderbilt.edu
(615) 343-9244

Project Title: [No title given]
Project Synopsis: preclinical cacner drug development and working with the
medicinal chemists in the VICB Program. The chemists create panels of molecular
targeted therapy that include anywhere from 25 to 50 compounds for each molecular
target that we then screen for their ability to enhance the efficacy of radiation therapy.
We are presently studying several different molecular targets which would each result
in publications for the Emphasis students. The students will do a semi-high throughput
screen on a cell biology assay (dye exclusion). They then choose the winner of the
panel and characterize its efficacy in both cell culture and animal models of cancer.
The publication would be the description of the efficacy of the best molecule out of the
panel.

Potential Mentor's Info.                     Additional Contact Info.
Dennis Hallahan
dennis.hallahan@vanderbilt.edu
(615) 343-9244

Project Title: [No title given]
Project Synopsis: Development of drugs that will protect the brain from cancer
therapy. In this project, medicinal chemists have created a panel of compounds that
protect neurons from cytotoxic therapy. The students will screen this library of 25
compounds to determine which of them is most effective at protecting neurons from
cancer therapy. The best compound will then be characterized in both cell culture and
animal models as neuroprotectors during brain radiotherapy. The students will do a
semi-high throughput screen on a cell biology assay (dye exclusion). They then choose
the winner of the panel and characterize its efficacy in both cell culture and mouse
models. The publication would be the description of the efficacy of the best molecule
out of the panel.

Potential Mentor's Info.                    Additional Contact Info.

Rizwan Hamid
rizwan.hamid@vanderbilt.edu
615-322-7601

Project Title: [No title given]
Project Synopsis: Acute leukemias represents a heterogeneous group of complex
disorders likely all arising from a transformed stem cell. Identification of genes and
pathways that play a role in stem cell regulation would provide insights into
pathophysiologic mechanisms of leukemias and help us design better diagnostic and
treatment options. My lab has three areas of active research. 1. Identification of genes
that play a role in acute leukemia biology. We use expression arrays, SNP arrays and
proteomic analysis in novel ways to identify new targets in leukemias. 2. Study of the
biological functions of the targets identified and determine their role in leukemia
biology. We use in vitro and in vivo assays of gene over-expression and knock-down
to study the role of these factors in normal and leukemic hematopoiesis 3. Effects of
single nucleotide polymorphisms (SNPs) on leukemic cell biology. There is a growing
body of evidence that suggests that genetic factors, SNPs, play an important role in
complex disease including cancer. We have asked the question whether SNPs have a
role in acute leukemia, particularly AML, biology. Our focus is to study the role SNPs
play in modulating the various developmental pathway of hematopoietic stem cells
and leukemogenesis.

Potential Mentor's Info.                    Additional Contact Info.

Eva Harth
                                            eva.harth@vanderbilt.edu
eva.harth@vanderbilt.edu
                                            615-343-3405
615-343-3405
                                            7619 Stevenson Center
Project Title: [No title given]
Project Synopsis: The rotation student will learn the synthesis and characterization of
organic nanoparticles that traffic peptides and siRNA molecules into cells. The
peptides/siRNA molecules are connected over an disulfide bridge that allows the
cleavage of the biological cargo in the reducitive environment of the cytosol.

Potential Mentor's Info.                     Additional Contact Info.

Alyssa Hasty
alyssa.hasty@vanderbilt.edu
322-5177 (office) / 322-5972 (lab)

Project Title: [No title given]
Project Synopsis: The growing worldwide obesity epidemic is frequently linked to
hyperlipidemia, inflammation, and insulin resistance leading to increased risk of
diabetes and cardiovascular disease. The long-term goal of my laboratory is to
determine mechanisms by which obesity increases risk for and pathophysiological
consequences of these devastating diseases. Macrophages are part of the innate
immune system that infiltrate white adipose tissue (WAT) in obese rodents and
humans, and produce most of the inflammatory cytokines and chemokines secreted
from WAT. In addition, their presence has been shown to be temporally associated
with the development of insulin resistance. My current research focus is to determine
mechanisms by which macrophages are attracted to WAT. We are targeting three
molecules: a chemoattractant protein, monocyte inflammatory protein-1α (MIP-1α),
saturated fatty acids (SFAs), and the adipokine leptin. A project related to any of these
molecules can be developed for the purposes of the Emphasis Program.

Potential Mentor's Info.                     Additional Contact Info.

Charles Hong
charles.c.hong@vanderbilt.edu
615-936-7032

Project Title: [No title given]
Project Synopsis: Small molecules that modulate biological processes have been
utilized for therapeutic purposes for thousands of years. While traditional small
molecule discovery had relied on serendipitous observations, modern advances in
synthetic chemistry and high-throughput screening have resulted in ever expanding
arsenal of chemical tools not just for pharmaceutical development, but also for the
study of fundamental biological processes. Our research is focused on studying
vertebrate development using chemical approaches, in a manner analogous to the
classic developmental genetic analysis. Using high-throughput chemical screens in
intact zebrafish, we identify small molecules that perturb development or reverse
zebrafish models of human diseases. The small molecules are then used as probes to
dissect such processes as artery-vein fate specification, heart development,
hematopoiesis, and embryonic dorsoventral axis formation. Since some of these
compounds will function by promoting development of specific cell and tissue types,
an important goal of our research is to develop chemical tools for stem cell research
and cell-based therapeutics. Importantly, some of these compounds have significant
therapeutic potential, and are being actively pursued as lead compounds for treatment
of specific human diseases.

Potential Mentor's Info.                    Additional Contact Info.

Charles Hong
charles.c.hong@vanderbilt.edu
615-936-7032

Project Title: [No title given]
Project Synopsis: Small molecules modulators of key developmental pathways that
are discovered using high-throughput chemical screens in zebrafish are utilized to
direct embryonic stem (ES) cells toward cardiac development. Project may involve 1)
discovery of additional small molecules in zebrafish, 2) discovering their biochemical
mechanism of action, or 3) efforts to replicate cardiac induction in human embryonic
stem cells or other stem cell types.

Potential Mentor's Info.                    Additional Contact Info.

Stacey Huppert
stacey.huppert@vanderbilt.edu
615-343-4024

Project Title: [No title given]
Project Synopsis: The goal of our lab is to explore how intercellular signaling
pathways are integrated in both developmental and disease responses of the liver. The
information gained from these studies will provide the framework to compare aspects
of liver development to the process of liver regeneration. We are initially examining
the role of the Notch intercellular signaling pathway in coordinating cell fate decisions
during liver development and regeneration. Possible projects: 1.Test the ability of
mouse embryonic stem cells and primary fetal hepatoblast cells via genetic deletion or
pharmacological inhibition to undergo the differentiation programs of hepatocytes and
cholangiocytes/biliary epithelial cells. 2.Analyze the capacity of various mouse Notch
pathway knockout mouse lines to undergo liver organogenesis in vivo and in vitro.
This will be done prior to the embryonic lethality period of day 9.5. We will determine
proliferation and morphogenesis of the liver bud and changes in expression of other
intercellular signaling pathway components. 3.Determine if loss of or activation of
Notch signaling affects Hepatocellular Carcinoma (HCC) progression. We will use a
tumor induction protocol in genetically modified mouse models and assess tumor
progression and markers of HCC. 4.Assess if Notch signaling plays a role in adult liver
regeneration models. Mice with conditional loss of or activation of Notch signaling
will be subjected to partial hepatectomy (the surgical removal of part of the liver).
After various periods of recovery we will analyze cell proliferation responses as well
as perform lineage tracing to determine which cells activate Notch during the
regenerative process.

Potential Mentor's Info.                     Additional Contact Info.
                                             Ann Hearn
Karen Joos
karen.joos@vanderbilt.edu                    615-936-1957
(615) 936-1957                               Vanderbilt Eye institute, 2311 Pierce
                                             Avenue
Project Title: [No title given]
Project Synopsis: The pioneering of laser surgery and ocular coherence tomography
by eye researchers has had a tremendous global health impact upon the current ability
to diagnose, treat, and monitor multiple eye diseases. The potential of combining these
two powerful modalities into a miniature intraocular probe to monitor and guide real-
time laser surgery is untapped. Surgical outcome advances will occur with new
devices to increase the technical precision of surgeons. This project proposes that a
system with a miniature probe can be designed that monitors real-time incision of a
tissue layer to protect the underlying tissues from injury. The imaging and lasing spots
will overlap on the target tissue to permit real-time imaging of tissue layer ablation as
the incision proceeds to the subretinal space. As this occurs, the probe will be moved
to an adjacent location to permit continued incision of the retina while preventing
damage to underlying retinal pigment epithelium. All incisions will be examined
histologically to evaluate for thermal injury, to inspect underlying tissue structures,
and to compare to the OCT signal profile to guide optimization of the probes.

Potential Mentor's Info.                     Additional Contact Info.

Karen Joos                                   Ann Hearn, admin assistant
karen.joos@vanderbilt.edu                    615-936-1957
(615) 936-1957

Project Title: [No title given]
Project Synopsis: Traumatic open globes/ lacerations or extensive retinal detachments
may lead to proliferative vitreoretinopathy following initial repair with subsequent
tractional retinal detachmens as glial remodeling occurs. Relaxing retinectomies to
incise a shortened and stiff retina are sometimes required to permit reattachment of the
retina in these difficult cases, but are associated with complications and a high failure
rate unless accompanied by radical anterior vitreous base dissections. An incising laser
wavelength such as 6.1 micron combined with real-time A-scan monitoring of the
incision depth may improve the retinectomy procedure outcomes and the surgical ease.
Statement of work: To enable the FEL to become clinically useful in performing
retinectomy, areas to be addressed in this proposal are: 1) compare the incising
capability of 6.1 micron FEL versus 6.45 micron FEL versus scissors retinectomy in
artificially detached retinas in animal cadaver eyes with BSS versus air, 2) build a low-
cost fiber-based A-scan instrument to monitor the incision depth in real-time and
combine it with the glass-hollow waveguide in an intraocular probe, 3) with the A-
scan evaluate real-time incising (retinectomy) of artificially detached retinas in animal
cadaver eyes with the optimal FEL wavelength, 4) evaluate all above incisions
histologically for collateral damage.

Potential Mentor's Info.                     Additional Contact Info.

Karen Joos                                   Ann Hearn, admin assistant
karen.joos@vanderbilt.edu
(615) 936-1957                               615-936-1957

Project Title: [No title given]
Project Synopsis: A glaucoma surgical procedure known as a trabeculectomy
produces a thin Tenons layer and overlying conjunctiva. A common long-term risk is a
trabeculectomy bleb leak with infection. After treating the infection, the leak is often
treated by surgical revision and conjunctival advancement. The qualified success rate
of this repair to maintain intraocular pressure at < 15 mm Hg was 5% at 5 years
Statement of work: To determine the optimal method for sealing leaks with
biomaterials, areas to be addressed in this proposal are: Year 1) compare the
adherences of amniotic membrane, Apligraf, and Dermagraft to cadaver conjunctival
holes following 561 nm irradiated Rose Bengal or 7.7 micron irradiated Tisseal
application. Year 2 2) perform a trabeculectomy and cut a hole in the bleb in 20
anesthetized porcine eyes and compare the 2 best treatments determined above
combined with sub-conjunctival injection of YFP-labeled porcine fibroblasts.
Examination of the wound integrity and the healing histologically at post-op day 2 in
the initial eye, and the immediate appearance following the acute procedure in the
contralateral eye would be performed.

Potential Mentor's Info.                     Additional Contact Info.

Spyros Kalams
spyros.a.kalams@vanderbilt.edu
322-8972

Project Title: [No title given]
Project Synopsis: Our laboratory studies cellular immune responses to intracellular
pathogens. We are evaluating quantitative and qualitative aspects of HIV-specific
CD4+ and CD8+ T cell responses in peripheral blood and in the central nervous
system. We have also developed a mouse model of tuberculosis and are determining
the correlates of protective immunity after vaccination. The latest project is focused on
developing a combined TB/HIV vaccine.

Potential Mentor's Info.                     Additional Contact Info.
Prince Kannankeril
prince.kannankeril@vanderbilt.edu


Project Title: [No title given]
Project Synopsis: A very powerful tool in assessing the arrhythmogenic substrate is
the intracardiac electrophysiologic study, during which spontaneous electrical activity
and that induced by programmed electrical stimulation of the intact heart are analyzed.
This approach, which has proven extremely valuable in the evaluation of patients with
arrhythmias, has now begun to be applied in genetically-engineered mice. Mouse
models with specific genetic lesions have the potential to elucidate the
pathophysiology underlying specific human diseases. In the murine EP lab, we apply
this technique to elucidate arrhythmia mechanisms in mice with specific genetic
lesions, of ion channel disorders, as well as cardiomyopathy models.
Electrophysiologic studies may identify subtle phenotypes in mouse models, not
observed with simpler testing. The student will develop the neccessary skills for rodent
surgery (internal jugular cutdown, use of operating microsope) as well as the tecniques
of the electrophysiology study. The student will also participate in data analysis, and
preparation of abstracts and manuscripts.

Potential Mentor's Info.                    Additional Contact Info.

Rachel Kuchtey
rachel.kuchtey@vanderbilt.edu
936-7190

Project Title: [No title given]
Project Synopsis: Glaucoma is a type of optic neuropathy with elevated intraocular
pressure resulting from impaired aqueous humor outflow as the most important risk
factor. The Kuchtey lab studies the mechanisms of optic nerve damage as well as
aqueous humor outflow impairment using a variety of molecular, cellular and
biochemical approaches.

Potential Mentor's Info.                    Additional Contact Info.

Bo Lu
bo.lu@vanderbilt.edu
39233

Project Title: [No title given]
Project Synopsis: [No synopsis given]

Potential Mentor's Info.                    Additional Contact Info.
Bo Lu
bo.lu@vanderbilt.edu
39233

Project Title: [No title given]
Project Synopsis: [No synopsis given]

Potential Mentor's Info.                     Additional Contact Info.

James May
james.may@vanderbilt.edu
6-1661

Project Title: [No title given]
Project Synopsis: Vitamin C, or ascorbic acid, recycles and preserves vitamin E, or α-
tocopherol in lipoproteins and cell membranes. Preservation of α-tocopherol protects
lipids from oxidant damage in diseases such as atherosclerosis and diabetes. This
laboratory has been involved in study of the mechanisms of this recycling at the
cellular level, as well as with how ascorbate and α-tocopherol help to prevent lipid
peroxidation in cell membranes. Ascorbate electrons are also transferred across the
plasma membranes of cells, and can reduce extracellular ascorbyl free radical. Study
of this extracellular ascorbate free radical reductase activity has also been an area of
interest. Recently, efforts have centered on study of the interactions of ascorbate with
the cells of the arterial wall, including endothelial cells, vascular smooth muscle cells,
and macrophages, to determine whether and how ascorbate can affect atherosclerosis.
Another area of interest is the role of ascorbate and vitamin E in mitigating damage
due to oxidant stress in neurons as this relates to Alzheimer’s disease. These studies
focus on the role of the transporter for vitamin C in neuronal function. Techniques
involved in these studies include: cell culture and fractionation, biochemical and
enzyme assays, HPLC, transgenic mice care and genotyping.

Potential Mentor's Info.                     Additional Contact Info.
                                             Carol Jackson
Robert Mericle
                                             carol.jackson@vanderbilt.edu
robert.a.mericle@vanderbilt.edu
                                             615-343-2452
(615) 343-2452
                                             T-4224 MCN
Project Title: [No title given]
Project Synopsis: My laboratory utilizes a well-established Subarachnoid hemorrhage
(SAH) model in the New Zealand white rabbit. This model has been used in my
laboratory to perform anaylsis of various medications on cerebral vasospasm following
SAH. Heparin has been described to decrease the negative effects of post-SAH
cerebral vasospasm, but this has not been weel-studied in a reliable animal model.

Potential Mentor's Info.                     Additional Contact Info.
Robert Mericle
robert.a.mericle@vanderbilt.edu
(615) 343-2452

Project Title: [No title given]
Project Synopsis: Analysis of several treatment strategies for reducing the cerebral
vasospasm associated with intracranial aneurysm rupture and subsequent subarachnoid
hemorrhage. This will be investigated in both the laboratory using an animal model as
well as in the hospital setting with patient-oriented research.

Potential Mentor's Info.                   Additional Contact Info.

Gregory Mundy                              Rita Burchett
gregory.r.mundy@vanderbilt.edu             riota.burchett@vanderbilt.edu
(615) 322-6110

Project Title: [No title given]
Project Synopsis: The two main areas of our research are (1) skeletal complications
of cancer, and (2) cell biology of bone remodeling. Our primary interests are in
understanding disease mechanisms and developing drugs for breast cancer metastasis,
myeloma bone disease, fracture repair and osteoporosis. We use a combination of in
vitro and in vivo preclinical models to examine the mechanisms responsible for bone
growth and bone metastasis, and for the discovery of new drugs.

Potential Mentor's Info.                   Additional Contact Info.
                                           Rita Burchett
Gregory Mundy
                                           rita.burchett@vanderbilt.edu
gregory.r.mundy@vanderbilt.edu
                                           (615) 322-6110
(615) 322-6110
                                           1235 MRB IV
Project Title: [No title given]
Project Synopsis: The two main areas of our research are (1) skeletal complications
of cancer, and (2) cell biology of bone remodeling. Our primary interests are in
understanding disease mechanisms and developing drugs for breast cancer metastasis,
myeloma bone disease, fracture repair and osteoporosis. We use a combination of in
vitro and in vivo preclinical models to examine the mechanisms responsible for bone
growth and bone metastasis, and for the discovery of new drugs.

Potential Mentor's Info.                   Additional Contact Info.

John Penn
john.penn@vanderbilt.edu
(615) 936-1485

Project Title: [No title given]
Project Synopsis: The Penn lab sponsors a number of independent projects that
concern the growth of new blood vessels in retinal tissue secondary to retinopathy of
prematurity, diabetic retinopathy and age-related macular degeneration. Both in vitro
and in vivo methods are used to define the molecular regulators of the angiogenic
process in the context of these conditions.

Potential Mentor's Info.                    Additional Contact Info.

Wellington Pham
wellington.pham@vanderbilt.edu
(615) 936-7621

Project Title: [No title given]
Project Synopsis: In this project we use optical and MRI imaging in order to track
dendritic cells (DCs) migration and homing in lymphoid tissue and learn how DCs
interact with other cells in the context of priming the immune system. Furthermore, we
use the MUC-1 transgenic mouse model to assess the effect peptide pulsed-DCs on
MUC-1 specific tumor. The project involves chemical development of molecular
probes, a transgenic mouse model, imaging techniques and most importantly is the
knowledge of immunology.

Potential Mentor's Info.                    Additional Contact Info.

Alvin Powers
Al.Powers@Vanderbilt.edu
615-936-7678

Project Title: [No title given]
Project Synopsis: Insulin secretion by pancreatic islets is tightly coupled to changes
in the blood glucose; abnormalities in insulin secretion are a major factor in both type
1 and type 2 diabetes. Our research is relevant to both type 1 and type 2 diabetes and
focuses on the following: 1) how pancreatic islets develop and maintain their blood
supply; we are applying this knowledge to pancreatic islet transplantation, an emerging
treatment of type 1 diabetes. 2) Interventions that may increase islet survival after
transplantation and increase the number of islet cells. 3) Islet function in type 2
diabetes and how the pancreatic islet responds to the insulin resistance of type 2
diabetes. 4) Developing in vivo bioluminescence and other technologies to image and
quantify pancreatic islets. Our research utilizes a variety of research approaches
including RNA and protein analysis, genetically modified mice, in vivo physiology,
gene transfer, and transplantation of murine and human islets and involves
collaborations with vascular biologists, development biologists, biomedical engineers,
and transplant biologists.

Potential Mentor's Info.                    Additional Contact Info.
Melissa Rhodes
melissa.rhodes@vanderbilt.edu
6159261762

Project Title: [No title given]
Project Synopsis: [No synopsis given]

Potential Mentor's Info.                    Additional Contact Info.

L. Roberts
jack.roberts@vanderbilt.edu
615-322-3203

Project Title: [No title given]
Project Synopsis: All non-steroidal antiinflammatory drugs (NSAID's) inhibit
inflammation by inhibiting the cyclooxygenase enzyme that forms prostaglandins
PG's). So the assumption has always been that NSAID's are antiinflammatory because
they inhibit PG's. However, many PG's are actually antiinflammatory. However, we
have discovered that highly reactive gamma ketoaldehydes (KA's) that are not PGs but
are also formed by the PG pathway and we have evidence that they are highly
inflammatory. The main problem with NSAIDs is that they cause stomach ulcers by
inhibiting PGs which exert beneficial actions in the stomach. We have developed
specific scavengers of these KA's and preliminary evidence suggests that they
effectively reduce inflammation. The project will involve the further development of
these KA scavengers and assess their efficacy to reduce inflammation in animal
models. If successful these studies could lead to the development of a new drug entity
that reduces inflammation without damaging the stomach

Potential Mentor's Info.                    Additional Contact Info.

Bernard Rousseau
bernard.rousseau@vanderbilt.edu
615-343-0862

Project Title: [No title given]
Project Synopsis: Vocal fold wound healing is believed to be uniquely different from
healing in other organs of the body because of the mechanical forces acting on the
tissue during vibration. The goal of our research program is to advance understanding
regarding the influence of voice use on organization and remodeling of the vocal fold
after injury. We use a combination of histology, immunohistochemistry, and molecular
biology techniques to investigate alterations in gene expression and extracelullar
matrix deposition of important mediators of vocal fold scar formation. In-vitro and in-
vivo experiments are also conducted to assess the impact of injury related tissue
alterations on biomechanical tissue properties and functional measures of phonation.
Current projects include the development of suitable methods for systematic control of
vocalization in animal wound models, investigation of the timing of vocalization on
gene expression and extracellular matrix deposition, effects of vocalization dose on
gene expression and the extracellular matrix, and development of a clinical database of
vocal outcomes following phonosurgery. The overarching aim of these projects is to
provide levels of evidence to support a standard of clinical care regarding post-
operative voice use. Ultimately, this line of research may result in improved
management of patients undergoing vocal fold microsurgery.

Potential Mentor's Info.                     Additional Contact Info.

Bernard Rousseau
bernard.rousseau@vanderbilt.edu
615-343-0862

Project Title: [No title given]
Project Synopsis: Vocal fold scarring results from inflammation and injury. Vocal
fold scar can be devastating for a professional singer or voice user who must rely on
singing and/or speaking as a source of income. Patients with vocal fold scar have
breathy, weak and often harsh vocal quality. Current management of vocal fold
scarring produces suboptimal results. New therapeutic modalities are being developed
in animal models using tissue engineering and cell based therapy to establish an ideal
treatment for this challenging clinical problem.

Potential Mentor's Info.                     Additional Contact Info.

Gregg Stanwood
gregg.stanwood@vanderbilt.edu
(615) 936-3861

Project Title: [No title given]
Project Synopsis: In utero exposure to cocaine produces permanent alterations in
dendritic morphology of cerebral cortical pyramidal cells, changes in gene expression
in subtypes of cortical interneurons, and a loss of dopamine D1 receptor signaling.
These abnormalities are elicited during a relatively brief period of embryonic
development, comparable to the second trimester in humans, and occur only in cortical
regions receiving dense dopaminergic input. Specific cognitive and motor behaviors
are altered in adult offspring as a result, and these behavioral deficits are reminiscent
of phentoypes observed in the affected human population. We hypothesize that these
(mal)adaptive changes are secondary to the loss of D1 receptor signaling, suggesting
that restoration of this signaling system may be an key therapeutic target. This project
will explore long-lasting alterations in D1-receptor signaling complexes, and D1-
mediated signal transduction cascades during normal brain development and following
prenatal cocaine exposure.

Potential Mentor's Info.                     Additional Contact Info.
David Tabb
david.l.tabb@vanderbilt.edu
(615)936-0380

Project Title: [No title given]
Project Synopsis: The Tabb laboratory focuses on the development and evaluation of
algorithms for producing biological information from mass spectrometry data. The
group emphasizes technologies to enable the use of mass spectrometry in support of
clinical research. Working in close collaboration with bench chemists of the Mass
Spectrometry Research Center, the group seeks to make useful software for
interpreting individual tandem mass spectra or data mining through the results for
large data sets. Particular strategies of interest include the application of statistical
models, graph theory, and parallel programming.

Potential Mentor's Info.                     Additional Contact Info.

Takamune Takahashi
takamune.takahashi@vanderbilt.edu
343-4312

Project Title: [No title given]
Project Synopsis: Diabetic nephropathy (DN) is the major single cause of end stage
renal disease in the United States. Growing evidence indicates that increased cellular
oxidative stress plays a central role in the pathogenesis of diabetic vascular
complications. Hyperglycemia and diabetes-associated factors, including advanced
glycation end products, angiotensin II, oxidized-LDL and inflammatory cytokines,
cause excessive superoxide (O2•–) production and results in diabetic vascular cell
damage. The superoxide dismutase (SOD) family of antioxidant enzymes is a major
antioxidant defense system against O2•–, dismuting superoxide into hydrogen
peroxide (H2O2) plus molecular oxygen. Furthermore, recent studies have shown that
SOD activity is significantly reduced in the patients with DN as compared with those
without nephropathy; however, the precise role of SOD in this disease remains
unknown. In the present proposal, we describe experimental approaches to determine
the role of SOD in DN. First, we will generate the diabetic mouse which accompanies
advanced DN by modifying the genetic background of Ins2+/C96Y diabetic mouse,
and examine whether decreases in renal SOD expression and activity are associated
with the development and progression of DN, comparing with DN-resistant C57BL/6
strain Ins2+/C96Y mice. Second, we will determine the role of SOD in DN by
genetically targeting SOD enzymes (CuZnSOD, MnSOD, and EC-SOD) in diabetic
mice. Finally, we will treat the diabetic mice with SOD mimetics and assess the
efficacy of SOD mimetic treatment to ameliorate DN. These complementary efforts
should determine the role of SOD in DN and explore a new anti-oxidant therapy for
this disease.

Potential Mentor's Info.                     Additional Contact Info.
Megha Talati
megha.talati@vanderbilt.edu
343-3312

Project Title: [No title given]
Project Synopsis: Heterozygous germline mutations in the bone morphogenic protein
type 2 receptor (BMPR2), a receptor for bone morphogenic protein (BMP), member of
the TGF-? superfamily, have been identified as a gene underlying familial pulmonary
arterial hypertension (FPAH). In FPAH intense structural remodeling of small
pulmonary arteries by different cell types, including endothelial (EC) and smooth
muscle cells (SMC), leads to increased pulmonary vascular resistance and subsequent
right ventricular failure. The target goals of the program are to identify the modifying
genes and environmental features that regulate the clinical expression of mutations in
BMPR2; to develop understanding about how BMPR2 mutations result in disease; and
to identify the undiscovered mutations which cause PAH. Our research plans are to
determine the functional mechanisms by which variations found in the BMPR2 alleles
alter BMP signal transduction and defining the biochemical effects of the mutant
proteins on signaling pathways. Our primary area of research is to 1] Determine
whether BMP-4 can activate SMAD independent pathways in control human PASMCs
and FPAH PASMCs. 2] Determine the proteins associated with BMP-BMPR2
complex at the cell membrane for activation of these SMAD independent pathways.

Potential Mentor's Info.                    Additional Contact Info.

Megha Talati
megha.talati@vanderbilt.edu
343-3312

Project Title: [No title given]
Project Synopsis: Heterozygous germline mutations in the bone morphogenic protein
type 2 receptor (BMPR2), a receptor for bone morphogenic protein (BMP), member of
the TGF-? superfamily, have been identified as a gene underlying familial pulmonary
arterial hypertension (FPAH). In FPAH intense structural remodeling of small
pulmonary arteries by different cell types, including endothelial (EC) and smooth
muscle cells (SMC), leads to increased pulmonary vascular resistance and subsequent
right ventricular failure. The target goals of the program are to identify the modifying
genes and environmental features that regulate the clinical expression of mutations in
BMPR2; to develop understanding about how BMPR2 mutations result in disease; and
to identify the undiscovered mutations which cause PAH. Our research plans are to
determine the functional mechanisms by which variations found in the BMPR2 alleles
alter BMP signal transduction and defining the biochemical effects of the mutant
proteins on signaling pathways. Our primary area of research is to 1] Determine
whether BMP-4 can activate SMAD independent pathways in control human PASMCs
and FPAH PASMCs. 2] Determine the proteins associated with BMP-BMPR2
complex at the cell membrane for activation of these SMAD independent pathways.
Potential Mentor's Info.                    Additional Contact Info.

Megha Talati
megha.talati@vanderbilt.edu
343-3312

Project Title: [No title given]
Project Synopsis: Heterozygous germline mutations in the bone morphogenic protein
type 2 receptor (BMPR2), a receptor for bone morphogenic protein (BMP), member of
the TGF-? superfamily, have been identified as a gene underlying familial pulmonary
arterial hypertension (FPAH). In FPAH intense structural remodeling of small
pulmonary arteries by different cell types, including endothelial cells (EC) and smooth
muscle cells (SMC), leads to increased pulmonary vascular resistance and subsequent
right ventricular failure. The mutations in BMPR2 can contribute to pulmonary tissue
remodeling especially in ECs and SMCs. Endothelin -1 (ET-1), a powerful
vasoconstrictor, is an important mediator in PAH. It activates a complex cascade of
intracellular events by binding to its specific receptors, ETA (localized only on SMCs)
and ETB (localized on both ECs and SMCs). Similarly, BMPs bind specifically to
BMPR2 and activates the canonic Smad signaling and mitogen-activated protein
kinase (MAPK) signaling pathways. Mutations in the BMPR2 gene may cause
alterations in these pathways as well as affect ET-1 synthesis and its downstream
signaling pathways. Our collaborator, has recently created a new ROSA26-tet-BMPR2
R899X transgenic mouse model which universally express inducible BMPR2 allele
(R899X) identified in four FPAH families, and exhibits a profound pulmonary
hypertensive phenotype. Our aim is to study whether mutations in the BMPR2 gene
affect expression of ET-1 and ET-1 receptors, and modulate Smad/MAPK activation
by ET-1 receptors in lung ECs and PASMCs.

Potential Mentor's Info.                    Additional Contact Info.
                                            Elaine Beeler
James Thomas
                                            elaine.beeler@vanderbilt.edu
james.w.thomas@vanderbilt.edu
                                            6513224746
615-322-4746
                                            T3219 MCN
Project Title: [No title given]
Project Synopsis: This project will use a mouse model of type 1 diabetes mellitus to
identify autoantibodies directed at novel beta cell autoantigens. Transgenic mice that
harbor a heavy chain immunoglobulin transgene will be used to restrict the normally
diverse repertoire of B lymphocytes that invade the islets in pre-diabetic NOD mice. B
lymphocytes will be captured from islets undergoing autoimmune attack and the
nature of there antigen receptors (heavy and light chains) will be determined.
Recurrently expressed receptors will be cloned and expressed as antibody molecules.
These recombinant antibodies will then be used to interrogate beta cell subtrates so
that novel targets of the autoimmune process will be identified.
Potential Mentor's Info.                      Additional Contact Info.

Vasundhara Varthakavi                         Beth Glascock
vasundhara.varthakavi@vanderbilt.edu          beth.glascock@vanderbilt.edu
343-5618; 343-5619(Lab)                       322-0811

Project Title: [No title given]
Project Synopsis: HIV-1 accessory gene product, Vpu is a potent regulator of viral
release from infected cells. Vpu functions by overcoming an innate host restriction to
viral release in human cells. In addition, Vpu alters the two major endocytic sorting
compartments including trans-Golgi network and recycling endosome. The goal of the
project is to define the precise molecular targets of the Vpu effect, and to evaluate their
role in the trafficking of HIV-1 Gag to its site of assembly/release.

Potential Mentor's Info.                      Additional Contact Info.

Jeremy Veenstra-VanderWeele
j.vvw@vanderbilt.edu
615-936-1701

Project Title: [No title given]
Project Synopsis: I began doing molecular genetic research in autism and obsessive
compulsive disorder during medical school and would love to mentor a medical
student interested in studying the molecular underpinnings of these common brain
disorders. The overall background of my research is given below. A student could join
in at any number of levels, from mouse behavior or neuroanatomy to protein
expression or gene regulation, depending on interest. Autism is the most heritable
common neuropsychiatric syndrome. The most consistent biological marker in autism
is elevated platelet serotonin (5HT) in one-third of patients. The serotonin transporter
(SERT) is responsible for uptake of serotonin in the platelet. Linkage studies in male-
only autism sibling pairs implicate the chromosome 17q11-21 region containing the
SERT gene (SLC6A4). Association findings implicate a common functional promoter
variant in SLC6A4 as a potential autism susceptibility or modulating allele.
Additionally, several rare functional amino acid variants in SLC6A4 are preferentially
transmitted to males with autism. Both the common HTTLPR variant and the rare
amino acid variants are particularly associated with elevated rigid-compulsive
behaviors in autism. I am applying genetic, molecular, cellular and behavioral
approaches to understand the impact of these variants on brain and behavior.

Potential Mentor's Info.                      Additional Contact Info.

Jorn-Hendrik Weitkamp
hendrik.weitkamp@vanderbilt.edu
(615) 343-9297
Project Title: [No title given]
Project Synopsis: We are studying the development of the cellular intestinal
immunity in the (preterm) infant and its relationship to the development of necrotizing
enterocolitis (NEC), an often fatal inflammatory disease of the intestine in preterm
infants. We are isolating proinflammatory and immune suppressor T cells from human
and mouse intestinal tissue and study their development at increasing gestational ages
and how this process is influenced by colonization of the gut with pathogenic bacteria
or probiotics. Isolated cells are analyzed for phenotype by flow cytometry and for
function by an array of T cell and cytokine assays. If interested, please email or call
me for more detailed information.

Potential Mentor's Info.                    Additional Contact Info.

Alison Woodworth
alison.woodworth@vanderbilt.edu
322-0905

Project Title: [No title given]
Project Synopsis: Substantial pregnancy loss occurs very early, after implantation and
before pregnancies can be detected by standard clinical measures or by home
pregnancy tests. Conceptuses that begin the implantation process and produce human
chorionic gonadotropin (HCG) are identifiable with a very sensitive assay for HCG.
With the advances in sensitivities of automated immunoassays, there have been reports
of detection of hCG in urine at concentrations consistent with early conception.
Studies have validated the quantitative measurement of hCG in urine, but never with
ample sensitivity to detect early pregnancy. The objective of this study will be to
develop and validate a rapid, quantitative assay to measure low concentrations of
HCG. This method then be used to monitor HCG concentrations in women with a
history of infertility who are attempting conception.

Potential Mentor's Info.                    Additional Contact Info.

Xiangli Yang
xiangli.yang@vanderbilt.edu
615 322 8052

Project Title: [No title given]
Project Synopsis: [No synopsis given]

Potential Mentor's Info.                    Additional Contact Info.

Xiangli Yang
xiangli.yang@vanderbilt.edu
615 322 8052
Project Title: [No title given]
Project Synopsis: [No synopsis given]

Potential Mentor's Info.                      Additional Contact Info.

Xiangli Yang
xiangli.yang@vanderbilt.edu
615 322 8052

Project Title: [No title given]
Project Synopsis: [No synopsis given]

Potential Mentor's Info.                      Additional Contact Info.

David Zealear
david.zealear@vanderbilt.edu
615-322-6167

Project Title: [No title given]
Project Synopsis: Bilateral vocal fold paralysis is a serious and often life-threatening
medical condition. Injury to the recurrent laryngeal nerves arrests the vocal folds in a
near-closed position. Conventional surgical therapies rely on partial laryngeal
resection to enlarge the airway, but sacrifice voice and leave the patient at risk for
aspiration. A more physiologic approach involves functional electrical stimulation of
the posterior cricoarytenoid (PCA) muscle to abduct the vocal folds during inspiration.
The goal of this research is to conceive an implantable laryngeal pacemaker system
that will reestablish bilateral glottal opening in synchrony with inspiration. Studies of
the safety and efficacy of an implanted laryngeal pacing system will be performed
initially in the canine, and then translated into the human through a clinical trial. After
adaptation to human anatomy, a prospective Phase I clinical trial of laryngeal pacing
treatment will be compared to tracheotomy and cordotomy with respect to ventilation,
voice and swallowing parameters. This new, more dynamic approach to treatment
could restore normal ventilation through the mouth without alteration of voice or
swallowing, and return the patient to a physically active lifestyle.

Potential Mentor's Info.                      Additional Contact Info.

David Zealear
david.zealear@vanderbilt.edu
615-322-6167

Project Title: [No title given]
Project Synopsis: Recent neurophysiological studies in the canine have demonstrated
that functional electrical stimulation (FES) of a paralyzed denervated muscle can
promote reestablishment of natural motoneuronal connections. Two hypotheses that
could explain how FES confers neuromuscular specificity have been proposed. The
first hypothesis holds that electrical stimulation maintains the motoneuron-muscle
fiber specificity that was established during development, and prevents its loss upon
denervation. The second hypothesis assumes that the concept of muscle plasticity
extends to its synapse, and that electrical stimulation can modulate receptivity of the
endplate for a particular type of motoneuron. The proposed research will distinguish
between these two hypotheses. A set of related experiments will be performed to
determine whether the selective effect of FES can be localized to either the nerve or
muscle. Laryngeal muscle reinnervation will be studied in canines chronically
implanted with stimulators that are bioengineered in the laboratory.

Potential Mentor's Info.                     Additional Contact Info.

Roy Zent
roy.zent@vanderbilt.edu
322-4632

Project Title: [No title given]
Project Synopsis: [No synopsis given]

				
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