Johns Hopkins Faculty:
Andrew Feinberg, Director
Department of Medicine
Email Dr. Feinberg
Dr. Feinberg did undergraduate studies at Yale and received his M.D. at Johns Hopkins. He carried out postdoctoral research in developmental biology at UCSD, and in molecular biology at Johns Hopkins, and subsequently was a Howard Hughes Medical Institute investigator at the University of Michigan. Since 1994, he has been the King Fahd Professor of Medicine, Molecular Biology and Genetics, and Oncology at Johns Hopkins. He and his colleagues identified altered methylation in human cancer, human imprinted genes and loss of imprinting in cancer, and the molecular basis of Beckwith–Wiedemann syndrome. He has developed several molecular methods, including random priming. Recently, his group has been studying the epigenetics of human complex traits in general, in a Center of Excellence in Genome Sciences (CEGS) awarded by the Genome Research Institute of the NIH.
Assistant Professor of Pharmacology and Molecular Sciences
Email Dr. Taverna
Eukaryotic cells package their genomes in the form of chromatin, which is comprised of histone proteins and DNA. Modification of chromatin by chemical marks affects how cellular machineries interpret the genome. The Taverna laboratory studies histone marks, such as lysine methylation and acetylation, and how they contribute to an “epigenetic/histone code” that dictates chromatin-templated functions like transcriptional activation and gene silencing. We use biochemistry and cell biology in a variety of model organisms to explore connections between gene regulation and proteins that “write” and “read” histone marks, many of which have clear links to human diseases like leukemia and other cancers. The lab also investigates links between small RNAs and histone marks involved in gene silencing.
Email Dr. Reddy
The focus of the research in the Reddy lab is to begin to understand how the nuclear periphery and other subcompartments contribute to general nuclear architecture and to specific gene regulation. Understanding the cell biology of genomes and how nuclear architecture controls gene expression is necessary to truly understand biological processes such as development and disease. Although sequencing of the genome and comparative genome analysis have yielded insights into the regulation and dis-regulation of genetic information, these efforts shed little light into how genomes actually work in vivo. The impact of architectural and cellular organization of genomes on gene activity is a next step to unlocking genetic and epigenetic mechanisms in development and disease. Specifically, they are trying to understand how genes are regulated at the nuclear periphery, decipher how genes are localized (or “addressed”) to specific nuclear compartments and, finally, determine how these processes are utilized in development and corrupted in disease
Department of Medicine
Email Dr. Onyango
.Dr. Onyango’s research is aimed at identifying the major players in protein acetylation and deacetylation in the mitochondria. He is dissecting the functions of these post-translational protein modifications in mitochondria biology, especially in apoptosis, metabolism, and aging. The lab’s goal is to build a (de)acetylation network(s) and to understand how defects in such network(s) might account for mitochondrial associated diseases like heart, kidney and liver diseases as well as cancer, infertility, diabetes and stroke.
Sidney Kimmel Comprehensive Cancer Center
The Baylin laboratory seeks to uncover the molecular basis for changes in cancer cell DNA which impairs important regulatory genes necessary to prevent the formation of tumors. These genetic changes are permanent in the DNA and cannot be reversed. The change studied by the Baylin and Herman labs is an alternative way in which cancer cells inactivate genes by adding methyl groups to the start regions of genes and this is associated with a "silencing" of the gene. Unlike DNA mutations, DNA methylation abnormalities are reversible by drugs in a laboratory setting and this reversal allows cancer cells to reactivate the silenced genes and produce normal protein. Understanding how the abnormal DNA methylation arises in cancer cells, and how this change leads to silencing of genes, is extremely important for enriching the possibility of reversing this process as a strategy to prevent and/or treat cancer.
Department of Biophysics
Visit the Bowman Lab - Email Dr. Bowman
Dr. Bowman received his Ph.D. at Princeton University and was a postdoctoral fellow at the University of California, Berkeley where he used X-ray crystallography to study cellular machinery involved in DNA replication. At Johns Hopkins his lab is focused on factors that package and physically reorganize chromosomes. Knowledge of the processes that drive remodeling are essential for gaining a more insightful understanding of human diseases that result from disruptions of normal gene regulation, such as cancer and inherited developmental disorders. Relatively little is known regarding the mechanism of by which ATP-dependent remodeling factors alter nucleosome structure, with no understanding of how distinct remodeler domains functionally interact to promote remodeling, how key remodeler domains are positioned in space with respect to one another, nor how remodelers embrace the nucleosome substrate. The long-term objective of the Bowman lab is to establish a biochemical and biophysical framework necessary for describing and understanding the processes driving chromatin remodeling.
Department of Biology, School of Arts & Sciences
Visit the Chen lab · Email Dr. Chen
Dr. Chen’s lab is interested in understanding epigenetic regulation in adult stem cell lineages. Adult stem cells have a unique ability to self-renew and produce daughters that differentiate into specific cell types. Mis-determination of stem cell fate and malfunction of stem cell derivatives are common causes of human diseases, such as tumors, tissue dystrophy, and infertility. Epigenetic changes that alter the expression of key regulators while preserving the DNA sequences underlie pathological progression to these diseases. The lab is using Drosophila male germline stem cell lineage as a model system to address the following questions: (1) Are there stem cell factors present and is the expression of these factors maintained by a unique chromatin structure? (2) How do the transcription and chromatin landscape change in continuously differentiating cells during normal development? (3) Can adult stem cells be regenerated if the differentiation process is reversed by the over-expression or ectopic expression of key regulators? (4) What features cause cells to become carcinogenic and does tempering such changes reduce cancer development? The lab is using a combination of molecular, genetic and biochemical tools, as well as developing new strategies to study the above questions at single-cell resolution.
Department of Pharmacology and Molecular Sciences
Visit the Cole lab · Email Dr. Cole
Dr. Cole is the E.K. Marshall and Thomas H. Maren Professor and Director of the Department of Pharmacology and Molecular Sciences at Johns Hopkins. His lab uses chemical approaches to study cell signal transduction, hormonal control of
circadian rhythm and gene regulation. He is interested in understanding the basis for molecular recognition of protein kinases. The lab employs substrate analogs, site-directed mutagenesis, and kinetic methods to elucidate protein kinase-substrate relationships. His lab also studies the mechanism and inhibition of melatonin production. His lab also developed selective HAT (histone acetyltransferase) inhibitors to investigate the role of the protein acetylation.
Department of Molecular Biology and Genetics
Email Dr. Corden
Dr. Corden’s lab focuses on mRNA biogenesis. The lab uses genetic and biochemical approaches in yeast and mammals to study the control of eucaryotic RNA polymerase II, particularly through its unusual repetitive domain at the C-terminus of the largest subunit. This C-terminal domain (CTD) is comprised of tandem repeats of the consensus sequence TyrSerProThrSerProSer. A major effort in the lab is directed at studies of proteins that bind the CTD.
Department of Epidemiology
Email Dr. Fallin
Dr. Fallin is interested in applying genetic epidemiology methods to studies of neuropsychiatric disorders including Alzheimer's disease, schizophrenia, autism, and bipolar disorder. She also works on the genetic predisposition to features affecting aging populations such as muscle strength and frailty. In addition to these applied projects, she is interested in evaluating and improving methods for genetic analysis of population data. This includes haplotype analysis and incorporation of large-scale SNP data. Her research focuses on methodology for population and family-based tests of genetic associations with human disease.
Department of Molecular Biology and Genetics
Email Dr. Greider
Dr. Greider is the Daniel Nathans Professor and Director of the Department of Molecular Biology and Genetics. Her lab focuses on understanding telomeres and telomerase and their role in chromosome stability, stem cell failure and cancer. By studying the biochemistry of telomerase and human telomerase RNA, they aim to elucidate the role of telomere maintenance in cancer in human and mouse cells. Her lab also studies a mouse model of telomere dysfunction and showed that the shortest telomere in a cell triggers a DNA damage response.
Department of Pathology
Email Dr. Iacobusio-Donahue
Dr. Iacobuzio-Donahue’s laboratory focuses on understanding the molecular basis for cancer metastasis as it relates to gastrointestinal cancer. To support her research she instituted the Johns Hopkins Gastrointestinal Cancer Rapid Medical Donation Program (GICRMDP) in 2003, a unique program that allows patients with terminal, metastatic cancer to agree to undergo a rapid autopsy for research into cancer metastasis. Her lab routinely applies molecular/cell biology and high-throughput genomic methods to understand those changes that impart the ability of a cancer cell to grow in an uncontrolled manner at the primary tumor site versus in target organs. Candidate genes or pathways identified through this work are further evaluated using a variety of models to explore their functional relationship to tumor progression, invasion and metastasis.
Department of Biostatistics
Email Dr. Irizarry
Dr. Irizarry has worked on Bioinformatics and Computational Biology problems for nine years. He has developed and published various widely used statistical methods for the analysis of microarray data. Two of his publications have been named Fast Breaking Paper, New Hot Paper, and Current Classic Paper in Mathematics by Thomson Essential Science Indicators (ESI). One of his publications won the 2004 American Statistical Association (ASA) Outstanding Statistical Application Award, which recognizes a paper that is an outstanding application of statistics in any substantive field. He was awarded the ASA Youden Award in Interlaboratory Testing for another of his publications. Dr. Irizarry also develops open source software implementing his statistical methodology. He developed the first extensible software library for the analysis of Affymetrix microarray probe-level data. His software tools have been downloaded over 20,000 times. He is also a leader and founder of the Bioconductor Project, an open source and open development software project for the analysis and comprehension of genomic data. Bioconductor provides the most widely used software tool for the analysis of microarray data. A book, co-edited by Dr. Irizarry and other project leaders, has sold over 10,000 copies in less than three years and has been translated into Chinese and Japanese. Dr. Irizarry has participated in various successful collaborations with Johns Hopkins University scientists. His collaborators include Jef Boeke, Aravinda Chakravarti, Andrew Feinberg, Jonathan Pevsner, and Sarah Wheelan. He has published over 40 collaborative papers. He is the Department of Biostatistics liaison to the Johns Hopkins Medical Institution’s Microarray Core. Dr. Irizarry is also a member of various international collaborative projects. He is a member of the NIC/OBBR-BRN Experimental Design Working Group, the GAIN Alternative Calling Algorithms Working Group, the EMERALD Project Scientific Advisory Board, and the MGED Advisory Board.
Department of Biostatistics
Email Dr. Ji
Dr. Ji works on developing statistical and computational tools for analyzing high-throughput genomic data generated by genome tiling arrays and next-generation sequencing. These transforming technologies provide the power to study gene expression, transcription factor binding, and DNA/histone modifications at the whole genome level. Using information collected by these technologies, Dr. Ji studies transcriptional regulation at both the genetic level and epigenetic level. At the genetic level, he develops methods for detecting transcription factor binding sites from ChIP-chip and ChIP-seq data, and methods for transcription factor binding motif discovery. At the epigenetic level, he studies how histone/DNA modifications and transcription factor binding jointly set up gene regulatory programs in development and diseases. Recently, he has started working with colleagues to develop approaches to analyzing allele-specific expression. In addition to methodology research, he develops software to deliver statistical methodologies to bench biologists. A recent example is the integrated system CisGenome for the analysis of ChIP-chip and ChIP-seq data.
Kennedy Krieger Institute
Email Dr. Kaufmann
As a behaviorally oriented neurologist, Dr. Kaufmann uses standardized behavioral tests and experimental paradigms to characterize the neurobehavioral phenotypes of Rett, Down, and Fragile X syndromes, focusing particularly on disorders of social interaction. He also uses mouse and other experimental models and neuroimaging data from subjects to investigate the neuroanatomical substrate of behavioral phenotypes in these disorders. Thirdly, in partnership with Dr. Joseph Bressler, Dr. Kaufmann studies the genes and proteins involved in these syndromes in order to identify the molecular profiles associated with specific neurobehavioral features. Recently, due to the association between mutations in the gene coding for the methylated DNA-binding protein Mecp2 and Rett syndrome, Dr. Kaufmann has become interested in the role of epigenetic mechanisms in developmental disorders.
Department of Psychiatry
Visit the Potash lab · Email Dr. Potash
Dr. Potash is co-director of the Mood Disorders Program and the director of the George Browne Psychiatric Genetics Laboratory. His research focuses on the genetic basis of major depression, psychotic bipolar disorder and the epigenetics of mood disorders. The lab uses SNP genotyping, DNA resequencing and gene expression studies to define genetic variations involved in susceptibility to mood disorders.
Dr. Reeves is Faculty Director of the Transgenic Core Facility and Director of the Post-Baccalaureate Research Education Program. The Reeves laboratory works on several aspects of the correspondingly complex phenotypes of trisomy using both animal models and studies in human populations. Down syndrome (DS) occurs as a result of Trisomy 21 and is among the most complicated genetic conditions compatible with human survival. The lab has developed and characterized mouse models that are useful for studies of aneuploidy and has initiated a multi-site consortium to identify human modifier genes that account for variability in the presentation of DS, beginning with congenital heart disease and cognitive skills. Definition of the timing and location of malformations, and identification of the gene(s) primarily contributing, forms the basis for genetic, pharmacologic and stem cell therapies to ameliorate these anomalies.
Dr. Wolberger is structural biologist who began working on mechanisms of transcription regulation as a graduate student at Harvard University. She completed postdoctoral work at the University of California, San Francisco and then at the Johns Hopkins University School of Medicine, where she is now Professor of Biophysics and BiophysicalChemistry and an Investigator in the Howard Hughes Medical Institute. Research in the Wolberger laboratory has focused on the fundamental mechanisms of gene regulation, using x-ray crystallography as a central tool for determining structures of protein-DNA complexes and of enzymes responsible for gene silencing. A current focus of research is on the Sir2 family of deacetylase enzymes, which play a central role in gene silencing in addition to regulating a variety of transcription pathways in humans. Dr. Wolberger and her colleagues also study the mechanism of telomeric silencing in yeast. Another research interest centers on the assembly of Lys63-linked polyubiquitin chains, which serve as signals in a variety of non-degradative pathways.
At other institutions:
University of Puerto Rico
National Human Genome Research Institute
Icelandic Heart Foundation