Program in Genetics and Genomics


	Stephanie Diezmann Ph.D. 2009 Postdoctoral Fellow Lab of Leah Cowen University of Toronto	Stephanie has a long-standing interest in the evolution and genetics of human fungal pathogens. She first came to Duke in 2001 as a visiting student to do a phylogenetic analysis of the evolutionary relationships among human pathogenic fungi together with Tom Mitchell and Rytas Vilgalys. The following year Stephanie returned to Durham to begin her dissertation research in Fred Dietrich’s laboratory. While in Fred’s lab she studied the evolution and genetics of oxidative stress in the model system Saccharomyces cerevisiae, which is usually benign but occasionally causes infections in humans. Stephanie showed that the yeast’s ability to survive oxidative stress, an important host defense mechanism, is a quantitative trait and clinical isolates are more resistant than strains from other ecological backgrounds such as the brewery or the vineyard. She mapped the phenotype and identified a single nucleotide polymorphism in a transcription factor that was not previously known to have a function in oxidative stress response. This SNP is partly responsible for increased peroxide survival in a clinical isolate. After successfully defending her thesis in January 2009, Stephanie swapped her flip-flops for warm boots and joined Leah Cowen’s laboratory in the Department of Molecular Genetics at the University of Toronto. In Leah’s lab she is pursuing her interest in fungal pathogenicity from a new angle. While DNA has featured prominently in her research so far, Stephanie is now investigating the effect the molecular chaperone heat shock protein 90 (Hsp90) has on host-pathogen interactions. Hsp90 has a profound impact on different facets of life by ensuring proper folding of other proteins, its clients. Leah and her lab have shown that Hsp90 promotes the evolution of antifungal drug resistance and affects cell morphology in response to elevated temperatures. Drug resistance and morphology contribute to virulence of Candida albicans, the yeast most commonly isolated in the clinic where it is the leading cause of fatalities due to mycotic infections. To explore Hsp90’s role in host resistance and fungal pathogenicity, Stephanie is screening a Candida albicans gene deletion library for mutants that are hypersensitive to Hsp90 inhibitors, assuming with the rationale that the proteins encoded by the missing gene in hypersensitive mutants are Hsp90 clients. Furthermore, Stephanie will be branching out from the fungal kingdom into the animal world by employing the nematode Caenorhabditis elegans as a model host to determine which Hsp90 clients in the worm are required for host resistance by using combinatorial RNA inference techniques on worms infected with C. albicans. The combined power of worm genetics and yeast pathogenicity provides new insights into the role that one of the cell’s key molecules plays in one of nature’s most intricate processes.

	Hanyi Zhuang Ph.D. 2008 Faculty Shanghai Jiatong University	Before coming to Duke, Hanyi Zhuang spent a year as a pre-doctoral fellow at NIH/NHGRI in Dr. Francis Collins' lab working on the causative genes of type II diabetes. After entering the Duke UPGG program, she first came to the lab of Hiro Matsunami in 2004 as a rotation student, joining the lab in April 2005. At that time, the lab had just identified RTP1, a protein that promotes functional expression of mammalian odorant receptors (Saito et al, 2004). Hanyi first showed that a short form of RTP1 was likely to be the bona fide RTP1 proteins that are functioning in the olfactory neurons. Using this, she developed a platform for high-throughput deorphaning of mammalian odorant receptors. The manuscript describing these results was published in Journal of Biological Chemistry (Zhuang and Matsunami, 2007). This finding was critically important for the entire lab as well as for the field, as it established a more efficient way to express odorant receptors. Hanyi also began a new project elucidating the molecular mechanisms underlying specific anosmia or smell blindness. She hypothesized that polymorphisms in odorant receptors might cause differences in individuals' olfactory abilities. Specific anosmia for androstenone is an ideal model to investigate her hypothesis. After obtaining a human odorant receptor that responds to androstenone and a related compound, androstadienone, using the aforementioned heterologous expression system, she identified a number of genetic variants of the receptor and showed that polymorphisms of this human odorant receptor can change its ability to respond to androstenone in vitro. In collaboration with Dr. Andreas Keller in Dr. Leslie Vosshall's group, who conducted psychophysical analyses, it was found that polymorphisms in the odorant receptor indeed contribute to the variability in human odor perception to androstenone and androstadienone. These results demonstrate the first link between the genetic variation of a human odorant receptor and odor perception, establishing the basis for the unravelling of olfactory coding. The manuscript describing these findings was published in Nature with Hanyi being a co-first author (Keller, Zhuang et al., 2007). She defended her Ph.D thesis in December 2007. Soon after graduation, Hanyi successfully secured a faculty position at Shanghai Jiaotong University in China, one of the best universities in the country, to start her own group.

	Sean Garvey Ph.D. 2007 Postdoctoral Fellow Lab of Brian Warmhoff University of Virginia	Sean Garvey trained as a UPGG student in the laboratory of Dr. Michael Hauser, where he studied limb girdle muscular dystrophy 1A through the use of mouse models. He is currently a postdoctoral fellow of Brian Wamhoff, identifying pharmacologic targets for heart disease in the Laboratory of Atherogenesis at the University of Virginia. Dr. Garvey was awarded Postdoctoral Fellowships by both the American Physiological Society and the American Heart Association.

	Jason Stajich Ph.D. 2006 Assistant Professor Plant Pathology & Microbiology University of California, Riverside	Jason Stajich completed his thesis, “A Comparative Genomic Investigation of Fungal Genome Evolution,” in April 2006. His graduate mentor was Dr. Fred Dietrich, a faculty member in the Department of Molecular Genetics and Microbiology. Using computational approaches, Jason analyzed patterns of gene family and gene structure evolution in samples of genomes of fungi. His research was in comparative biology of these genomes using samples of closely related species and across an entire kingdom. During his time as a graduate student, he also established collaborations with mycologists and evolutionary biologists across the university through the interdisciplinary nature of the UPGG. Jason was also awarded an NSF Graduate fellowship that provided a stipend for his final three years of graduate school. Upon graduating from the UPGG in 2006, Jason continued to pursue his interest in fungal evolutionary biology and was awarded a three-year postdoctoral fellowship through the Miller Institute for Basic Research in Science at University of California, Berkeley. His faculty sponsor is Dr. John Taylor, a faculty member and co-chair of the Department of Plant and Microbial Biology. In the summer of 2008 he accepted a faculty position at the University of California, Riverside as part of their bioinformatics faculty search and will begin as an Assistant Professor of Bioinformatics in July 2009 in the Department of Plant Pathology and Microbiology. His laboratory will pursue research in fungal biology and evolution using computational, comparative, and experimental techniques.

	Jon S. Zawistowski Ph.D. 2005 Postdoctoral Fellow Dept. of Pharmacology UNC, Chapel Hill	Jon S. Zawistowski completed his graduate studies with Doug Marchuk. There Jon worked on the functional characterization of the gene products involved in an inherited form of stroke and seizure called cerebral cavernous malformations. The Marchuk lab had identified two novel genes that, when mutated, cause this autosomal dominant disease. Jon showed that these gene encoded proteins involved in an integrin/MAP kinase signaling pathway controlling endothelial cell function. His work implicated these pathways in the proper function of the vascular system of the brain. Jon is currently a Postdoctoral Fellow in the lab of Klaus Hahn at the University of North Carolina, Chapel Hill, where he is working on molecular sensors to detect cell signaling in vivo. These small molecule probes will fluoresce whenever a signaling protein phosphorylates its target. These would be used to monitor signaling microscopically in vivo, allowing real-time investigation of signaling at the sub-cellular level. Jon was awarded postdoctoral fellowships from the Josephine Peiser Charitable Foundation/American Cancer Society and the American Heart Association to pursue this work.

	Erich S. Huang Ph.D. 2002 Assistant Professor Department of Surgery Duke University Medical Center	After finishing his Ph.D. in 2002, Erich Huang completed his last year of medical school at Duke University and entered the General Surgery Residency program. He did his Chief Residency year in 2007-2008 and joined the Department of Surgery as an Assistant Professor in July 2008. His research goals are: (1) defining sparse latent factors in gene expression datasets that are indicative of components or "modules" of biological pathway activity in colorectal neoplasia; (2) using computational methods to phenotype malignant and premalignant lesions that stochastically "shuffle" these modules and fit a phenotypic model in accordance with the biology of that specific sample; (3) develop a high-throughput "module" assay for phenotyping samples in order to begin performing large RNAi library screens that define relationships between modules. Ultimately he plans to use this assay as a discovery tool for directed combination therapy, whether in colorectal or other neoplastic disease. The Surgery Department is making an effort to cultivate the research careers of a few junior faculty in keeping with the tradition of Duke being a very research-focused academic surgical department.

	Amy Gladfelter Ph.D. 2001 Assistant Professor Department of Biological Sciences Dartmouth College	For her Ph.D. work in Daniel Lew's laboratory, Amy Gladfelter studied a small GTPase called Cdc42p, which is a conserved regulator of cell polarity and cell shape. She demonstrated that cycling of Cdc42p between GDP- and GTP-bound forms is required for stable septin ring assembly in budding yeast cells and that GTPase activating proteins (GAPs) can act as effectors of small GTPases. Previously, Cdc42p was thought to function simply as an "on-off" switch which signaled in an activated, GTP-form. Her experiments provided evidence that Rho-type small GTPases can also function as "timers" in which the actual rate of cycling contributes to an output such as the construction of a septin ring. After receiving a Ph.D. from the UPGG program in September 2001, Amy began post-doctoral training in the laboratory of Peter Philippsen at the University of Basel, Biozentrum in Basel, Switzerland. She received an NSF post-doctoral fellowship and a Roche Research foundation fellowship to support her post-doctoral work. During that time, she identified and analyzed an asynchronous nuclear division cycle in a multinucleated fungal cell. This discovery was remarkable because it demonstrated that individual nuclei can autonomously commit to division within one cytoplasm. As all nuclear proteins are synthesized in the shared cytoplasm and many proteins shuttle continuously between the cytoplasm and the nuclei, the mechanisms enabling asynchrony are mysterious. Nuclear autonomous behavior has also been observed in multinucleate tumors, in cell cycle checkpoint activation, with gene expression in myoblasts and cells of the placenta; however, in no case has the mechanism of asynchronous behavior within one cell been examined. Her work as a post-doc and now in her own lab has led to the development of this new model system to study how signaling pathways are compartmentalized and restructured based on cell architecture. Amy started her own laboratory at Dartmouth College in the Department of Biological Sciences in January 2006. She has built a research group with 3 Ph.D. students, a technician, a post-doctoral fellow and three undergraduates. She is the recipient of a Basil O'Connor Award from the March of Dimes, pilot project grants from the American Cancer Society and Norris Cotton Cancer Center, and a 4-year project grant from the NSF.