Membership   Michael Bustin, Ph.D. Dr. Bustin's research focuses on the role of chromosomal proteins in chromatin function, gene expression, development and cancer. The current focus is on the cellular function of HMGN proteins.   Susan Gottesman, Ph.D. Dr. Gottesman studies novel mechanisms for gene regulation and how these mechanisms contribute to global control circuits in the E. coli model system. Her current investigations focus on small regulatory RNAs and energy-dependent proteolysis.   Shiv Grewal, Ph.D. Dr. Grewal investigates the epigenetic control of higher-order chromatin assembly in the S. pombe model system. He has shown that RNA interference (RNAi), whereby double-stranded RNAs silence cognate genes, plays a critical role in targeting of heterochromatin complexes to specific locations in the genome.   Gordon Hager, Ph.D. Dr. Hager’s interests lie in the role of chromatin structure in gene regulation, the mechanism of steroid receptor function, and the architecture of active genes in the interphase nucleus. His lab examines nuclear receptors as important models in understanding chromatin modification and restructuring.   Michael Lichten, Ph.D. Dr. Lichten studies the genetic recombination, DNA damage repair, and chromosome structure in S. cerevisiae, with a focus on events that occur during meiosis.   Tom Misteli, Ph.D. Dr. Misteli uses molecular techniques in combination with live-cell microscopy to study gene expression in the intact nucleus of living cells. He has developed novel imaging techniques to explore gene and protein function at the molecular level in living cells and his laboratory is applying these methods to understand the contribution of genome organization to differentiation and disease.   Andre Nussenzweig, Ph.D. Dr. Nussenzweig examines the mechanisms by which cells monitor and repair DNA double-strand breaks. His research goals are to: 1) elucidate the mechanisms by which oncogenic translocations form, 2) determine the influence of chromatin structure on the maintenance of genomic stability, and 3) decipher the complex interplay between DNA damage detection, signaling, and repair.   Thomas Ried, M.D. Dr. Ried investigates the role of genomic instability and associated gene expression changes during cancer development. He is analyzing aneuploidy as a molecular marker for cancer diagnostics and identifying gene expression signatures that assist in disease prognosis and therapy.   Jeffrey Strathern, Ph.D. Dr. Strathern is interested in understanding the mechanisms of genetic recombination and gene regulation in S. cerevisiae. Currently, he is screening for strains defective in recombination to define additional functions involved DSB repair.   Carl Wu, Ph.D. Dr. Wu studies chromatin regulation of eukaryotic gene expression in the yeast, fly, and mouse model systems. His research focuses on how genes are dynamically unmasked by ATP-driven, multi-component chromatin remodeling enzymes, and the physiological significance of this process.   Amar Klar, Ph.D. Dr. Klar studies: 1) the fission yeast mating-type switching and gene silencing; 2) implications of the yeast work to explain development of human hand-use preference, brain laterality, scalp hair-whorl orientation, schizophrenia and bipolar disorders, and the mouse visceral left-right axis determination; and 3) the mechanism of selective DNA strand segregation in mouse cell mitosis.   Peter Aplan, M.D. Dr. Aplan studies the mechanisms that lead to recurrent, non-random chromosomal translocations associated with hematologic malignancies in mouse and human cells.   Thomas Hornyak, M.D. Dr. Hornyak studies the role of polycomb proteins in melanocyte transformation and melanoma development and the identification, characterization, and function of melanocyte stem cells.   Kathrin Muegge, M.D. Dr. Muegge studies how heterochromatin controls gene silencing during embryogenesis and tumorigenesis.   Victor Zhurkin, Ph.D. Dr. Zhurkin uses computer techniques to study the sequence-dependent DNA deformability and its role in nucleosome positioning and formation of the higher-order chromatin structure.   Dhruba Chattoraj, Ph.D. Dr Chattoraj studies DNA replication and segregation with a focus to understand how these processes are coordinated with the cell cycle in a multi-chromosome bacterium Vibrio cholerae.   Dinah Singer, Ph.D. Dr. Singer studies the multiple molecular mechanisms that regulate the tissue-specific and dynamic patterns of MHC class I gene expression in vivo, focusing on transcriptional mechanisms, chromatin structure and boundary elements and their relationship to the biological function of the class I molecule in providing immune surveillance.   William Bonner, Ph.D. Dr. Bonner investigates the mechanisms of DNA double-strand break repair, emphasizing those related to ?-H2AX focus formation at the sites of DNA double-strand breaks. He analyzes the impact of defects in these mechanisms on genome integrity, cancer, and aging.   David Symer, M.D., Ph.D. Dr. Symer studies transcriptional and genomic variation due to endogenous transposons in mouse and human genomes. His laboratory focuses on epigenetic controls and consequences of active transposition.   James McNally, Ph.D. Dr. McNally's primary focus is on the in vivo dynamics of transcription factor binding, and its role in transcription. A secondary focus is on the structure and function of higher order chromatin at sites of active transcription.   Kevin Gardner, M.D., Ph.D. Dr. Gardner's group is applying genomic approaches to study the mechanisms of transcriptional co-regulator function and targeted chromatin modification in response to mitogenic signaling and cell cycle progression in lymphoid cells. Two transcriptional co-regulators currently under investigation by the group are the p300 histone acetyltransferase and the breast cancer associate gene BRCA1.   Munira Basrai, Ph.D. Dr. Basrai has two research projects: 1) Molecular mechanisms of faithful chromosome transmission and cell cycle checkpoint control in S. cerevisiae and humans and 2) Functional genomics of previously unidentified small open reading frames (sORFs). Her current research efforts are focused on the structure of specialized centromeric chromatin and how it influences genome stability.   Sheue-yann Cheng, Ph.D. Dr. Cheng’s work focuses on the understanding of molecular mechanisms of thyroid hormone receptor (TR) action. TRs are ligand-dependent transcription factors. She is interested in understanding how the gene regulating activity of TRs is modulated by nuclear coregulator proteins via modifying the chromatin structure.   Mikhail Kashlev, Ph.D. Dr. Kashlev’s research interests include: 1) identification of protein factors and mechanisms leading to establishment and maintenance of epigenetic modifications of genes in eukaryotes, 2) the study of TCR and transcription fidelity toward mammalian RNA polymerase II, and 3) understanding the basic mechanism of transcriptional pausing, arrest and termination using RNA polymerase from E. coli.   Yawen Bai, Ph.D. Dr. Bai’s research uses biophysical techniques including NMR and amide hydrogen exchange to investigate the dynamic processes of nucleosome assembly/disassembly and structures of histone chaperones complexed with histones.   Mirit Aladjem, Ph.D. Dr. Aladjem investigates genetic and epigenetic regulation of DNA replication in mammalian cells. Her laboratory examines mechanisms that transmit signals from the cell cycle regulatory network to chromatin to determine where and when DNA replication initiates during normal cell cycle progression and after exposure to anti-cancer drugs.   David Levins, M.D., Ph.D. Dr. Levens’ lab studies the interrelationship between DNA topology, DNA conformation and gene expression. In particular we are focusing on a class of sequence specific, super-coil sensitive, single strand DNA binding transcription factors (FBP1, FBP2, FBP3, and FIR) that impose real-time regulation on c-myc and other genes. The supercoiling forces required for binding are generated by ongoing transcription and dynamically transmitted to susceptible sites within the genome.   Shyam Sharan, Ph.D. Dr. Sharan research is to directed towards understanding the role of Breast cancer susceptibility genes BRCA1 and BRCA2 in maintaining the genomic integrity using mouse models.   Yikang Rong, Ph.D. Dr. Rong’s lab uses the fruitfly Drosophila as a model to elucidate the mechanisms that distinguish the natural ends of a chromosome (telomeres) and broken ends of a chromosome (DNA double strand breaks).   Maxwell Lee, Ph.D. Dr. Lee’s research focuses on understanding the genetic and epigenetic mechanisms of cancer etiology using an integrative systems biology approach - "cancer genomics and epigenomics". We have been using gene chips to study genome-wide chromatin modification (ChIP-on-chip), human methylome characterization, and gene expression in both normal and cancer cells.   Paul Meltzer, M.D., Ph.D. Dr. Meltzer’s research interests are focused on the characterization of genetic alterations in cancer cells, the mechanisms that lead to their development and their effects on gene expression. To address these issues, Dr. Meltzer and colleagues utilize several genomic technologies, especially DNA microarray hybridization.   Vladimir Larionov, Ph.D. Dr. Larionov’s research interests focus on the structure and function of the human centromere. They exploit Human Artificial Chromosomes HACs with synthetic alphoid DNA as a tool for functional and structural analyses of the human kinetochore.   Charles Vinson, Ph.D. Dr. Vinson’s research focuses on the B-ZIP family of transcription factors (AP1, C/EBP, and CREB). His group has designed a dominant negative that inhibits the DNA binding of these proteins and produces clinically relevant phenotypes when they are expressed in transgenic mice. In addition, his team is using Chip-ChiP data to determine the location of these proteins in the genome to help understand their mechanism of action.   Bruce Paterson, Ph.D. We are studying muscle development in Drosophila at the transcriptional and post transcriptional levels. The major steps in Drosophila muscle formation involve 1) the determination of the myogenic field in the mesoderm, 2) selection and segregation of the muscle founder cells, 3) seeding the proper founder cell pattern which determines muscle position and identity, and 4) activation of the muscle-specific gene set in the post mitotic muscle fiber. Changes in gene expression/regulation and chromatin structure/function underlie this entire process. As an entry point we are analyzing the role of the muscle-specific bHLH transcription factor in Drosophila, called nautilus (MyoD). Nautilus expression is the earliest marker for founder cells and its function is required to establish the correct founder cell/muscle pattern. Nautilus converts non-muscle cells to muscle cells, a process likely involving chromatin remodeling, and may point to one of its important roles during development. In addition, nautilus activates miRNAs and is regulated by miRNAs itself, placing nautilus as both a transcriptional and post- transcriptional regulator of myogenesis.   David Schrump, M.D. Dr Schrump's work focuses on epigenetic mechanism of gene expression in lung cancer cells, and the utilization of DNA demethylating agents and histone deacetylase inhibitors for lung cancer therapy. Additional laboratory efforts pertain to the characterization of epigenetic alterations in normal respiratory epithelia mediated by tobacco smoke.   Yamini Dalal, Ph.D. Dr. Yamini Dalal studied DNA sequence effects on nucleosome positioning and linker histone H1 modulation of chromatin structure in vitro and in vivo in mouse during her graduate years at Purdue University in the laboratory of Dr. Arnold Stein. She then moved to the Fred Hutchinson Cancer Research Center to work with Dr. Steven Henikoff on the centromere-specific histone variant CenH3 and studied its influence on nucleosome and chromatin structure using Drosophila as a system. Her laboratory interests focus on understanding how chromatin structure influences epigenetic mechanisms involved in important biological functions.