Rajeev
Ayyagari
Matthew
Blahna
Haiming Cao,
Ph.D.
Lana
Dinic
David
Fardo
Meg
Gustafson
Jessie
Hsu
Erin
Johnson, Ph.D.
Kihwa
Kang, Ph.D.
Jun
Kawasaki
David Kim,
Ph.D.
Clifford
Meyer, Ph.D.
Edward
Ruiz-Narvaez
Jeremy
Stuart, D.Sc.
Kelvin
Tsai, M.D.
Sara
Vallerie
Katy
Wellen
Hongying
Zhong
Li Ye
Rajeev Ayyagari is a predoctoral student in the
Department of Biostatistics. He has a unique background in both biostatistics
(BSc and MS degrees at Indian Statistical Institute) and computer science (MS
degree from University of Maryland). His efforts have been largely focused on
computational aspects of statistics (data mining and statistical learning
theory) and during his MS degree, he designed efficient algorithms for data
mining problems and computationally intensive statistical applications.
Recognizing that he wished to pursue research in an academic setting, he applied
to our program with the "desire to be at the center of progress in this
interdisciplinary effort, rather than contribute from the edges."
Matthew Blahna is a HSPH predoctoral student in the
Biological Sciences in Public Health (BPH) program. Matt has a BS and MPH
degrees from the University of Michigan. His efforts have been largely focused
on population dynamics responsible for the emergence of antimicrobial resistant
pathogens. His previous thesis work in the MPH program at UMichigan examined the
dissemination of virulence factors and antibiotic resistance genes among
uropathogenic E. coli and he is first author of a paper reporting the
distribution of trmethoprim-sulfamethoxazole resistance genes among uropathogens
in Europe and Canada. He also is coauthor on a paper examining the population
dynamics of a newly proposed uropathogenic E coli clonal group and he is
finishing work with researchers at the Center for Molecular and Clinical
Epidemiology of Infectious Disease to utilize microarray technology for gene
discovery in pathogenic and commensul E coli. Recognizing that his "goals
require a mulit-disciplinary and inter-departmental education" he applied to our
to obtain basic biological research training since his goals "require the
utilization of molecular biology laboratory techniques, epidemiological surveys
and nonlinear systems models".
Haiming Cao, Ph.D. (Biochemistry,
University of Nevada-Reno): Postdoctoral fellow co-mentored by Drs. Gokhan
Hotamisligil and Alexander Ivanov at Harvard School of Public Health. Fatty acid
binding proteins play critical roles in inflammatory and metabolic responses.
Using gene expression profiling, Haiming is studying mouse models deleted in the
fatty acid binding protein aP2 and mal1 to characterize the effects of diet
induced obesity on adipocyte gene expression. He will also collaborate with the
HSPH proteomics core, under the supervision of Dr. Ivanov, to identify protein
interactions and potential post-translational modification of fatty acid binding
proteins. These studies will eventually be extended to use ‘lipidomics’ in order
to characterize the content of lipid bodies and how these organelles are
regulated by fatty acid binding proteins. Haiming’s project combines
state-of-the-art high throughput analytical techniques to address outstanding
questions about metabolic syndrome.
Lana Dinic is a HSPH predoctoral student in the Biological Sciences in Public Health (BPH) program. Lana has a BS degree in Life Sciences from Mt. Holyoke College. She applied to our program “motivated by a passion for making meaningful contributions to knowledge that will address problems in human disease”. In particular, her interests lie in reducing the impact of infectious disease on global health, and she is seeking to develop expertise in the area of molecular biology of pathogenic organisms.
David Fardo:
Predoctoral student, PhD candidate in the Department of Biostatistics.
David examined the effects of differing phenotype characterizations on the power
to detect a disease susceptibility locus / phenotype association. Specifically,
his project used R-based simulations of trios (simulated genotype and phenotype
of one offspring and genotypes of both parents) to compare the power of family
based association tests (FBATs) when using a continuous trait against different
rules of dichotomizing the trait. These simulations were carried out using a
progression of reasonable assumptions regarding heritability, allele frequency
and sample size in order to gauge how the different dichotomizations affect
power in varying situations.
Meg Gustafson Gregor: HSPH predoctoral student in the BPH program. Meg has begun to study the role of Stamp 1 and 2 proteins in cellular metabolism. Stamp2, a six-transmembrane protein with oxido-reductase capabilities, has been shown to be necessary for proper insulin signaling in adipose tissue. However, little is known about its mechanism of action. Stamp1 is a highly homologous family member with a different tissue profile, predominantly expressed in the brain and prostate, and present at lower levels in the kidney, spleen, and white adipose tissue. Its function is as yet unidentified. Cell culture and mouse models are the primary tools used to investigate the metabolic functions of the Stamp molecules and their importance in maintaining appropriate insulin signaling
Jessie Hsu: Predoctoral student in the Department of Biostatistics. She has combined training with a BS degree from the University of Washington as a double major in biochemistry and statistics. Her research experience as a Howard Hughes Medical Institute Research Intern at the Fred Hutchinson Cancer Research Center in Seattle was her inspiration for pursuing a PhD in biostatistics. She studied nucleotide diversity in human olfactory genes with an aim to quantify genetic variation and to describe selective pressures underlying allelic diversity. This background in computational biology fit well with the training the Roadmap program seeks to provide. Jesse’s ultimate goal is to be a "biostatistician at a research institution …[to] engage in collaborative research with scientists and doctors."
Erin Johnson, Ph.D. (Medical Sciences, Medical
College of Ohio): Post-doctoral fellow co-mentored by Drs. Marianne
Wessling-Resnick and Megan Murray. Erin's project is to investigate the
relationship between reticuloendothelial iron status (specifically regulated by
the iron export protein, ferroportin) and intracellular Mycobacterium
tuberculosis (M.tb) growth and infection. Conducting experiments with a pathogen
such as M.tb requires extensive BL3 level training. Erin is in the process of
finishing this training and will be able to operate independently following
completion of the final skills test. While training, Erin also conducted several
experiments with the BL2 level Mycobacterium bovis-BCG aimed at discerning a
role for ferroportin in modulating intracellular mycobacterial growth. These
preliminary experiments helped to develop a novel immunofluorescence-based
approach for quantifying intracellular bacteria using scanning cell microscopy.
The results suggest that ferroportin is a negative regulator of intracellular
mycobacterial growth. Erin was also a co-author on a paper exploring a similar
role for ferroportin in regulating the growth of Salmonella, another obligate
intracellular pathogen. In addition to performing bench work, Erin is also
participates in weekly group meetings held by Dr. Murray. These meetings are
conducted to discuss and coordinate active tuberculosis epidemiology studies
being carried out in both South Africa and Peru. An ultimate goal is to
translate findings on disease progression and human genetic variation into a
model system for cell culture studies.
Kihwa Kang, Ph.D. (Food Microbiology and
Toxicology, University of Wisconsin-Madison): Postdoctoral fellow co-mentored by
Drs. Chih-Hao Lee and Frank Hu at Harvard School of Public Health.
Hypertriglyceridemia is frequently associated with obesity and metabolic
diseases including insulin resistance. Based on the findings that nuclear
receptor PPAR delta senses dietary lipids and regulates fat catabolism, the
hypothesis behind Kihwa's project is that PPARd is a key regulator of metabolic
homeostasis and insulin sensitivity. Her project examines the effect of receptor
deletion on glucose and lipid metabolism as well as on insulin signaling using
mouse models. As nuclear receptors control biological processes through
transcriptional regulation, she seeks to identify target genes of PPAR in
critical metabolic pathways to dissect the molecular mechanism by which PPAR
regulates metabolism. After establishing the role of PPAR in metabolic
homeostasis and insulin sensitivity, she will test gene-diet interactions by
examining whether PPAR delta polymorphisms modify the effects of dietary fatty
acids and carbohydrates on risk of developing obesity, the metabolic syndrome,
and type 2 diabetes. A large cohort study led by Dr. Frank Hu lends itself to
this interdisciplinary investigation.
Jun Kawasaki is
a HSPH predoctoral student in the Biological Sciences in Public Health (BPH)
program. Jun has a BA in Biology from Grinnell College and enters our program
with a keen interest in cancer research. She seeks to pursue questions about
signal transduction pathways critical for tumor development from both cellular
and clinical aspects, using genetic and molecular approaches. Her undergraduate
research studies focused on nutritional products that have chemopreventive and
chemotherapeutic effects, and her findings were recently presented at the
Experimental Biology 2006 meeting, which she was invited to attend last April.
Jun’s broad interests fit in well with the interdisciplinary nature of our
program.
David Kim, PhD (Environmental Sciences and
Engineering, The University of North Carolina at Chapel Hill): Postdoctoral
fellow co-mentored by Drs. Thomas Smith (Harvard School of Public Health) and
Guido Guidotti (Harvard College). In the last decade, a number of important
discoveries have been made regarding the role of membrane proteins (i.e.,
transporters). Transporters are expressed at higher concentrations in the
epithelium of the stomach, intestines, kidneys, liver, and brain. They can
restrict the access of many compounds to the central nervous systems, decrease
the bioavailability of drugs, and limit the transport of teratogens to the
fetus. Despite the overall significance of transporters, their role in
determining the pharmacokinetic behavior of environmental toxicants is poorly
understood. The objectives of David’s study are (1) to identify environmental
toxicants that can potentially interact with transporters, and (2) to examine
the relative importance of transporters for the bioavailability of environmental
toxicants. The hypothesis behind David’s project is that transporters will
decrease the toxicity of environmental contaminants by restricting uptake into
the systemic circulation and increasing clearance. David will implement
computational tools to examine the structural and functional properties of
chemicals that interact with transporters. He will use the results from this
analysis to develop quantitative structure-activity relationship (QSAR) models
that are predictive of pharmacokinetic parameters, such as the maximum efflux
rate. David will also develop a quantitative description (i.e.,
physiologically-based pharmacokinetic model) of the interaction between
chemicals and transporters, and use this description to predict the
bioavailability of chemicals. The results of David’s project will contribute to
a better understanding of and ability to predict individual risks from exposures
to environmental toxicants.
Clifford Meyer, Ph.D. (Chemical Engineering, Princeton University): Postdoctoral fellow co-mentored by Drs. Shirley Liu and Myles Brown at DFCI. Their joint research project was on chromatin immunoprecipitation (ChIP) tiling arrays and the development of analysis software that is reliable, easy-to-use and capable of representing important features of the data and their relation to the genome. Cliff's particular interests reside in normalization of raw data, data filtering, ChIP-enriched region location and the identification of binding sites and features of the genome such as protein coding sequences and motifs.
Edward Ruiz-Navaerez:
HSPH predoctoral student, and DSc candidate in the 
Departments of Epidemiology and Nutrition. Apolipoprotein
CIII (apoCIII) and AV (apoAV) regulate triglyceride metabolism in opposite ways.
Also, several studies have shown that naturally occurring sequence variation in
both APOC3 and APOA5 genes affects plasma triglyceride levels, but evidence for
an association with risk of coronary heart disease (CHD) is scarce. Edward's
work involved analysis of single nucleotide polymorphisms (SNPs) in the APOC3
and APOA5 genes to determine whether haplotypes defined by these genetic
variants are associated with the risk of nonfatal myocardial infarction (MI) in
the Costa Rican population. He also examined whether haplotypes interact with
non-genetic factors (for example, diet) on the determination of MI risk or
plasma lipid concentrations.
Jeremy Stuart,
D.Sc. (Cancer Cell Biology, Harvard School of Public Health):
Post-doctoral fellow co-mentored by Drs. Zhi-min Yuan and Gokhan Hotamisligil.
One of the most over-looked aspects of obesity-associated disorders is the
predisposition to tumors. Jeremy tested the hypothesis that adipose tissue
produces factors that modulate the growth of tumor cells and contribute to the
cancer risk associated with weight gain. To address this question, he studied
the interaction between adipocytes and tumor cells in vitro using a 3D cell
culture approach. The ultimate goal being to identify adipocyte derived factors
regulating tumor growth in vitro.
Weidong Tian, Ph.D. (Bioinformatics,
Washington University): Postdoctoral fellow co-mentored by Drs. Fritz Roth and
Heather Nelson. Weidong’s project took advantage of the fact that non-melanoma
skin cancer, which is the most frequently diagnosed malignancy in humans, can
serve as a model for understanding genetic susceptibility to cancer. Working
with Dr. Fritz Roth, Weidong plans to develop a principled candidate gene
approach applying a fully integrated probabilistic model for predicting genes
potentially involved in skin cancer development. His work in this area will
greatly benefit from the co-mentorship of Dr. Heather Nelson, who has strong
expertise in epidemiology and the biology of skin cancer. She has developed a
large population-based case control study of skin cancer in New Hampshire, and
with access to DNA from this population, Weidong can directly test the
association between variants in candidate genes and case status in Dr. Nelson’s
epidemiologic study. Variation in genes that modify UV exposure, as well as
those involved in DNA damage response and repair are known to affect individual
susceptibility to skin cancer, thus we viewed this particular research project
to be in keeping with our training goal for interdisciplinary research in
molecular biology, epidemiology, and biostatistics in a team-oriented
environment with the prospect of developing a novel candidate gene approach to
mapping complex traits.
Kelvin Tsai, M.D.: HSPH graduate
of the BPH program. Kelvin employed heterotypic coculture models to study the
interactions between mammary stromal fibroblasts and epithelial cells. This
model system explores the effects of low-level stress and cell premature
senescence on breast morphogenesis and carcinogenesis. His work led to a first
author paper published in Cancer Research.
Sara Vallerie: HSPH predoctoral student, BPH program. Sara's
projects focused on elucidating the roles of JNK1 and JNK3 in the metabolic
syndrome. JNK1 and JNK2 have already been shown to be key players in
obesity-associated disease. Using molecular and cellular biology, physiological,
and biochemical techniques, Sara explored their roles in metabolic disease. Sara
was recently awarded an individual NRSA to support her efforts.
Katy Wellen: HSPH graduate of the BPH program. Katy's project focused on understanding the metabolic role of a poorly understood protein called Stamp2. Found primarily in adipocytes and regulated by both nutritional and inflammatory stimuli, this protein may represent a point of intersection for metabolic and inflammatory pathways. Katy used both cell culture and mouse models to investigate the role of Stamp2 in adipocyte function and whole body energy metabolism. She has several manuscripts pending publication from her studies.
Li Ye is a HSPH predoctoral student in the Biological
Sciences in Public Health (BPH) program. He graduated from Tsinghua University
with a BS degree in Biological Sciences this June. He has twice received a First
Prize Scholarship for academic excellence from Tsinghua University, and was a
Gold Medal winner in the National Biology Olympiad of China in 2002. He is
seeking to apply his talents to systems biology, and in his statement he
indicated that he was attracted to our program because of its "integrated
multidisciplinary approaches÷.not only [have we] covered essential issues such
as genetic basis, stress responses and metabolic regulation of diseases, but
also investigated them at the mechanism level as well as in the context of
population studies".
Hongying Zhong, Ph.D. (Chemistry, University of Alberta): Postdoctoral fellow associated with Proteomics Core in a joint research project led by Drs. Dieter Wolf, Alexander Ivanov, Gokhan Hotamisligil, Frank Sacks, Louise Ryan and Eric Rimm. This combined research effort focused on identifying biomarkers for metabolic disease, including diabetes and coronary heart disease, using plasma proteomics. Hongying's role in this team-directed effort was to devise standardized plasma sample preparation affording sensitivity, reproducibility and throughput. Mouse models of metabolic disease were used to develop and test this technology.