Research in the Department of Human and Molecular Genetics at Virginia Commonwealth University spans the spectrum of gene discovery, functional genomics, diagnostics and therapeutics. Research in the department falls into four main categories.
Cancer Molecular Genetics and Experimental Therapeutics
Paul B. Fisher, M.Ph., Ph.D.
Dr. Fisher’s laboratory focuses on three broad areas: cancer, neurodegeneration and infectious diseases. Using subtraction hybridization and other techniques, the laboratory has cloned a number of novel genes. Experiments are aimed at elucidating mechanisms of action and roles in various disease states. The primary objectives are to translate laboratory discoveries into the clinic for improved diagnosis, prevention and therapy of cancer, neurodegeneration and infectious diseases. Dr. Fisher collaborates with Drs. Sarkar, Su and Wang.
Zheng Fu, Ph.D.
Dr. Fu's research programs focus on understanding the molecular mechanisms of the control of the cell cycle and maintenance of the genomic stability, understanding how misregulation of those physiological processes contribute to carcinogenesis and applying the findings to develop novel and targeted cancer therapies as an improved way of preventing and treating cancers.
Joseph W. Landry, Ph.D.
Dr. Landry studies how chromatin remodeling complexes and histone modifying enzymes regulate chromatin structure and ultimately gene expression. These mechanisms of gene regulation show promise as novel targets for small molecule therapeutics, which could inhibit metastasis and immune system avoidance by tumor cells.
Devanand Sarkar, M.B.B.S., Ph.D.
Dr. Sarkar focuses on understanding the molecular mechanism of carcinogenesis, especially hepatocellular carcinoma (HCC), and utilizing that knowledge to develop novel and targeted cancer therapeutics. The current studies predominantly involve Astrocyte Elevated Gene-1 (AEG-1), its downstream molecules and interacting partners in the context of HCC.
Xiang-Yang Wang, Ph.D.
Dr. Wang studies stress response and its key players (e.g., stress proteins), ‘danger’ sensing pattern recognition molecules (e.g., scavenger receptors) in inflammation, pathogen recognition and immune homeostasis. They are also involved in the preclinical development and evaluation of novel immuno-modulating approaches to treat malignancies and other inflammatory diseases.
Jolene Windle, Ph.D.
Dr. Windle employs genetically engineered mouse tumor models to examine the effect of specific genetic alterations on tumorigenesis. These include studies to compare the effects of p53 gain-of-function and loss-of-function mutations, as well as the effects of different ras oncogenes, on a wide range of tumor properties. Dr. Windle also directs the VCU Transgenic/Knockout Mouse Core, and collaborates with a number of other investigators on the development of novel mouse cancer models.
Neurogenetics, Neurodegeneration and Deafness
Paul B. Fisher, M.Ph., Ph.D.
Dr. Fisher studies neurodegeneration and is interested in translating laboratory discoveries into the clinic for improved diagnosis, prevention and therapy.
Mike Grotewiel, Ph.D.
Dr. Grotewiel uses the genetic model organism, Drosophila melanogaster (fruit fly), to investigate the molecular basis for ethanol-related behaviors and oxidative damage. Since the fundamental aspects of gene function are conserved throughout the animal kingdom, information from the Drosophila studies in the Grotewiel laboratory should be applicable to alcohol use disorders and other diseases in humans. Dr. Grotewiel is a member of and collaborates with other members of the the VCU Alcohol Research Center directed by Drs. Mike Miles (Pharmacology and Toxicology) and Ken Kendler (Psychiatry). Dr. Grotewiel also collaborates with Drs. Scott Gronert (Chemistry), Rita Shiang (Human and Molecular Genetics) and Paul Fisher (Human and Molecular Genetics).
Rita Shiang, Ph.D.
Dr. Shiang’s laboratory has identified one gene, CISD2, which causes Wolfram Syndrome. Wolfram syndrome is a neurodegenerative syndrome with diabetes as an additional symptom. Her laboratory is exploring the cellular consequences of knocking down the gene in neuronal and beta pancreatic islet cell lines.
Developmental Genetics and Differentiation
James Lister, Ph.D.
Dr. Lister studies the gene networks that control development of neural crest cells in the zebrafish, focusing on the role of the transcription factors mitfa and foxd3 in pigment cells. Dr. Lister’s lab is also investigating the function of mitf genes in eye development and melanoma. Additional projects include the construction of zebrafish models of human genetic disorders and new tools for manipulating the fish genome.
Joyce A. Lloyd, Ph.D.
Dr. Lloyd’s laboratory is interested in developmental gene regulation and uses globin switching as a model system. The major focus of this research project has been to identify the DNA regulatory elements and transcription factors controlling globin gene switching. Using knock-out mice the laboratory has shown that EKLF and KLF2, related zinc finger transcription factors, regulate embryonic globin gene expression. Currently the laboratory is studying the mechanism of action of EKLF and KLF2 in erythropoiesis and globin gene expression. New work in the laboratory includes studying the roles of KLF2 and KLF4 in cardiovascular development. Dr. Lloyd collaborates with Drs. Jack Haar and Gordon Ginder at VCU.
Rita Shiang, Ph.D.
Dr. Shiang uses model systems, including cell lines, zebrafish and mice to explore craniofacial development. She studies the gene mutated in Treacher Collins Syndrome, a syndrome that affects the bones in the face, primarily the lower jaw. Shiang collaborates with James Lister, Ph.D.
Jolene Windle, Ph.D.
Dr. Windle has a major interest in the use of genetically modified mice to study the contribution of various genes to both normal bone development and to various disease states in the bone. She has a particular interest in Paget’s disease of bone, in which both genetic and environmental factors contribute to the development of focal bone abnormalities, and she has developed a variety of transgenic and knockout mouse models for investigating the molecular basis of the etiology of this disease.
Quantitative and Behavioral Genetics
Lindon J. Eaves, Ph.D., D.Sc., MA (Oxon)
Dr. Eaves Lindon Eaves' interests embrace, but are not confined to, the study of human variation, with particular focus on human behavior and its disorders. His research encompasses the development of mathematical models that reflect competing theories of the causes and familial transmission of human differences, the design of studies for the resolution, analytical methods for parameter estimation and hypothesis-testing and application to substantive questions about specific human traits.
Hermine H. Maes, Ph.D.
Dr. Maes addresses basic etiological questions regarding the transition from tobacco use to nicotine dependence; examining the role of genetic and environmental factors contributing to progression of tobacco use into nicotine dependence between adolescence and young adulthood. With collaborators in the Department of Psychiatry one research goal is to characterize the functional properties of nicotinic receptors implicated in nicotine dependence to increase our understanding of the etiology, development, heterogeneity and comorbidity of smoking. Along with Dr. Michael Neale (Psychiatry), she is a co-investigator on the “Open Mx: Multipurpose Software for Statistical Modeling” project to develop powerful software for statistical analysis of large and complex datasets.
Judy L. Silberg, Ph.D.
Dr. Silberg is a clinical psychologist by training and her research focuses on the complex interplay of genetic and environmental factors in the development of behavioral and emotional disorders in children, adolescents and young adults. She has spearheaded the collection of several genetically informative datasets including: The Virginia Twin Study of Adolescent Behavioral Development (VTSABD); the Young Adult Follow Up (YAFU) of the VTSABD and; the Children of Twins Study (COT) of adult twins, spouses, and their children for studying the nature of transmissible risk from parents to their children.
Timothy P. York, Ph.D.
Dr. York studies the contribution of genetic and environmental factors that regulate the duration of pregnancy. Current research includes assessing the extent to which the fetal and maternal genomes interact with aspects of the social environment and how this might explain the large difference in the mean gestational age at birth between racial groups. This and other studies utilize developments in statistical genetic methodology to identify robust information from whole-genome measures (e.g., epigenetics, gene expression, cytogenetics, microbiome and allelic variation) using cross-platform data integration methods. Genetically informative family studies (e.g., discordant MZ twin design) are used to increase the signal to noise ratio in highly multi-dimensional data.