The following list of program faculty members is provided in two groups: Research Laboratory Mentors and Clinical Training Faculty. The first group includes faculty who have either recently served as research laboratory mentors of our residents or fellows or who are representative of faculty who would be appropriate research laboratory mentors. Opportunities are not limited to this group of faculty, and new faculty may be added based a particular resident or fellow's research interests and approval by a committee of faculty members. Our residents and fellows function as research postdoctoral fellows in the laboratories of these representative faculty members and are engaged fully in all aspects of laboratory research including preparation of manuscripts. In addition, residents and fellows are exposed to the NIH grant process. The second group includes faculty who are integral members of the training program and provide clinical training, clinical research and teaching. Residents and fellows gain exposure to patients that may provide research and collaborative opportunities, and clinical faculty provide valuable mentoring on professional development activities.
Research Laboratory Mentors
Frederick Alt, Ph.D., CHB Department of Pediatrics, Center for Blood Research
(
http://www.hms.harvard.edu/dms/bbs/fac/alt.html)
The broad focus of the Alt laboratory is the elucidation of mechanisms involved in maintenance of genomic stability in mammalian cells. More specifically, the laboratory studies the mechanism and control of antigen receptor variable region gene assembly (VDJ recombination) in developing B and T lymphocytes and the mechanism of immunoglobulin heavy chain class switch recombination (CSR) and somatic hypermutation in activated mature B lymphocytes. A major current focus of the laboratory is the elucidation mechanisms by which the interplay of DNA repair and cell cycle checkpoint mechanisms acts to suppress genomic instability, lymphomas, and solid tumors.
David Altshuler, M.D., Ph.D., MGH Department of Molecular Biology, Center for Human Genetic Research
(
http://www.hms.harvard.edu/dms/bbs/fac/altshuler.html)
A major focus of Dr. Altshuler's research is to characterize human genome sequence variation. His laboratory has been actively involved in the International Haplotype Map Consortium. A second major focus is to apply the tools of high-throughput SNP genotyping and statistical genetics to understand type 2 diabetes and other diseases with genetic risk factors. The long-term goal of his laboratory's research in identifying genetic risk factors is to understand how they contribute to human pathophysiology and to apply such information to improve diagnosis, prevention and treatment of disease.
Alan Beggs, Ph.D., CHB Department of Medicine, Division of Genetics
(
http://www.hms.harvard.edu/dms/bbs/fac/beggs.html)
Dr. Beggs' research is aimed at understanding the structure and function of proteins that make up skeletal muscle fibers. One approach underway involves identifying and characterizing new skeletal muscle genes and proteins. The second entails identifying genetic mutations that cause human neuromuscular disease. These simultaneous approaches should enable them to correlate their basic muscle biology findings with their studies on muscle tissue in patients with neuromuscular diseases. The diseases under study include nemaline myopathy, myotubular myopathy, congenital fiber type disproportion (CFTC), multiminicore disease, and congenital myopathies with non-specific muscle findings.
David Beier, M.D., Ph.D., BWH Department of Medicine, Division of Genetics
(
http://www.hms.harvard.edu/dms/bbs/fac/beier.html)
Dr. Beier's research focuses on mouse genetics, including novel techniques for rapid gene mapping and on the rapid recovery of novel mouse mutations derived from ENU mutagenesis by mapping and gene identification in silico. The screen for recessive ENU-induced mutations of late embryonic development is targeted to identify models of human malformation syndromes which affect organogenesis. Also, genetic analysis is used to characterize complex traits, such as modifier loci affecting the progression of polycystic kidney disease and interacting loci causing asthma in a mouse model.
Susan Bonner-Weir, Ph.D., BWH Department of Medicine, Joslin Diabetes Center
(
http://joslin.org/732_1835.asp)
Dr. Bonner-Weir's laboratory has been studying the islets of Langerhans and concentrating on three areas of research: (1) the architecture of the islets and implications for their function, (2) the regulation of the number of islet cells in the body, and (3) the factors involved in islet growth and differentiation. Now, Dr. Bonner-Weir's main focus is the search for new sources of insulin-producing beta cells. Dr. Bonner-Weir's laboratory has shown that new islets can be formed in vitro from duct cells that have been isolated from the adult human pancreas. This finding offers hope that such duct cells might one day be used to provide islets for transplantation, possibly obviating the need for immunosuppressive drugs if the transplanted islets could be derived from the patient's own cells.
Constance Cepko, Ph.D., HMS Department of Genetics
(
http://www.hms.harvard.edu/dms/bbs/fac/cepko.html)
Dr. Cepko and her associates are interested in the mechanisms that direct development of the central nervous system (CNS) of vertebrates, focusing on the vertebrate retina. One approach is to generate an accurate description of the progenitor-progeny relationships in several areas of the CNS. To achieve this, Dr. Cepko's laboratory developed a technology for mapping the lineages of cells in vivo. Various genomics approaches are used including SAGE and microarrays to identify genes and functional approaches such as retroviral transduction or electroporation in vivo or in vitro to misexpress genes.
George Church, Ph.D., HMS Department of Genetics
(
http://www.hms.harvard.edu/dms/bbs/fac/church.html)
Dr. Church's research interests include the use of quantitative whole genome and proteome measures to guide computational modeling of regulatory and enzymatic networks in microbial and mammalian cells. Technologies are being developed based on bioinformatics, microarrays, mass spectrometry, automation, multiplexing, micro fluidics, and homologous-recombination genome engineering. These methods are being used to discover new regulatory motifs involved in cell cycle control, stress response, and many other network components.
Karen Cichowski, Ph.D., BWH Department of Medicine, Division of Genetics
(
http://www.hms.harvard.edu/dms/bbs/fac/cichowski.html)
The general focus of the Cichowski laboratory is to investigate signaling mechanisms underlying cancer and related developmental processes. To achieve this, a multi-faceted investigative approach is being taken; combining mouse modeling techniques with basic biochemical and cell biological studies. This approach provides a powerful means of dissecting gene function on a molecular and cellular level, as well as in the context of tumorigenesis and development. Lab members are studying the NF1 tumor suppressor gene. Because NF1 patients are also predisposed to developing brain tumors, myeloid malignancies, and may exhibit cognitive deficits and bone deformities, NF1 is implicated in a wide variety of tissues and disease processes.
Douglas Cotanche, Ph.D., CHB Department of Otolaryngology
(
http://www.childrenshospital.org/cfapps/research/data_admin/Site182/mainpageS182P0.html)
The goal of Dr. Cotanche's work is develop therapies to treat sensorineural hearing loss through two investigational routes: 1. to define and harness the mechanisms that regulate the regeneration of hair cells--which line the cochlea and transmit sound to the auditory nerve, and 2. to replace lost hair cells with a stem cell line, in a sense forming an artificial cochlea. In the first research pathway, Cotanche is looking at hair cells in chickens--one of the few animals capable of regenerating the cells once they are lost. In the second line of research, he is seeking to develop a line of stem cells that can be implanted in the cochlea and induced to divide and differentiate.
Joseph Coyle, M.D., HMS Department of Psychiatry, McLean Hospital
(
http://www.mclean.harvard.edu/research/mrc/lpmn.php)
The focus of the laboratory of Dr. Coyle is the glutamatergic neurotransmitter system and its involvement in neurotoxicity models. Major studies going on in the lab at present include: (1) Mechanisms involved in the delayed kainic acid mediated toxicity in vitro and in vivo. The critical role of oxidative stress, elevated intraneuronal CA2+ levels, programmed cell death and developmental expression of glutamate receptor subtypes are examined. (2) Characterization of NAAG and NAALADase and their role in neuro-psychiatric disorders. To better understand the relationships between NAAG and glutamate neurotransmission, he is currently undertaking a detailed molecular characterization of NAALADase to determine its localization and regulation of expression, and defining abnormalities of NAAG and NAALADase levels in neuropsychiatric disorders, including schizophrenia, Huntington's Disease and Alzheimer's Disease.
Alan D' Andrea, M.D., DFCI Department of Radiation Oncology and Pediatrics
(
http://www.hms.harvard.edu/dms/bbs/fac/dandrea.html)
The D' Andrea laboratory examines the molecular signaling pathways which regulate the DNA damage response in mammalian cells. The primary focus is the molecular pathogenesis of human chromosome instability syndromes, particularly Fanconi Anemia (FA). His research program addresses several aspects of this novel signaling pathway including: (1) the assembly, transport, and structure of the FA protein complex, (2) the enzymatic monoubiquitination and deubiquitination of the D2 protein, (3) the function of the chromatin-associated FA complex in cell cycle checkpoints and homologous recombination DNA repair, and (4) the identification of novel interacting proteins in these complexes.
Elizabeth Engle, M.D., CHB Department of Medicine, Division of Clinical Genetics
(
http://www.childrenshospital.org/cfapps/research/data_admin/Site163/mainpageS163P0.html)
Dr. Engle's research combines clinical, genetic, and molecular biological approaches to the study of strabismus and ocular motoneuron development. Her work is focused on studies of the 'congenital fibrosis syndromes,' ophthalmoplegic disorders in which primary gaze is aberrant and the eyes are unable to move in one or multiple directions causing significant visual impairment. Her hypothesis is that the subset of disorders termed 'congenital fibrosis of the extraocular muscles' (CFEOM) result from aberrant development of the oculomotor and/or trochlear nuclei, and that Duane syndrome (DS) results from aberrant development of the abducens nucleus.
Judy Garber, M.D., M.P.H., DFCI Department of Medical Oncology/Population Sciences
(
http://www.dfhcc.harvard.edu/membership/member-profile/member/493/0/)
Dr. Garber's research interests include the process and outcomes of BRCA1/2 clinical testing. The goals of her research are: (1) to identify factors predicting better outcomes of BRCA1/2 genetic testing in women undergoing clinical testing, and (2) to identify factors predicting uptake of genetic testing among physicians.
James Gusella, Ph.D., MGH Department of Neurology, Center for Human Genetic Research
(
http://www.hms.harvard.edu/dms/bbs/fac/gusella.html)
Dr. Gusella's laboratory is focused on understanding nervous system disease using molecular genetic strategies, beginning with human patients and proceeding through in vitro and modeling studies. Dr. Gusella's laboratory is currently searching for susceptibility and modifier genes in Parkinson's disease and Huntington's disease, and, as part of the Developmental Genome Anatomy Project, identifying genes at the breakpoints of balanced translocations associated with developmental abnormality. Lab members are also examining the mechanism of pathogenesis of genetic defects in biotin-responsive basal ganglia disease, Huntington's disease, neurofibromatosis, and torsion dystonia and pursuing assays to identify genetic or chemical modifiers in some of these disorders, with the ultimate goal of developing an effective rational therapy. Finally, the Gusella laboratory is involved in efforts to apply both morphometric and functional imaging studies aimed at providing novel phenotypes for analysis of the genetic underpinnings of behavior and cognition.
Emanuela Gussoni, Ph.D., CHB Department of Medicine, Division of Genetics
(
http://www.hms.harvard.edu/dms/bbs/fac/gussoni.html)
Dr. Gussoni's research involves identification and characterization of human muscle-derived stem cells and the optimize action of the use of muscle-derived stem cells for cell-based therapy of muscular dystrophy. These cells are being studied via microarray analysis. A goal of this project is to identify genes specifically expressed by muscle stem cells. Further, these cells are being expanded to obtain sufficient numbers for optimizing in vivo delivery protocols into mice with muscular dystrophy.
Daniel Haber, M.D., Ph.D., MGH Department of Medicine
(
http://www.hms.harvard.edu/dms/bbs/fac/haber.html)
The Haber laboratory is interested in the genetics of cancer, with primary emphasis on the characterization of tumor suppressor genes implicated in breast cancer and Wilms tumor, and the identification of somatic mutations linked to drug susceptibility in lung cancer. Cells with inducible expression of distinct WT1 isoforms, combined with microarray expression profiling and chromatin-immunoprecipitation libraries are used to search for transcriptional targets of WT1 that underlie its effect on cellular differentiation and tumor suppression. Ongoing studies of the checkpoint kinase CHK2 in cancer-prone families are aimed at developing functional assays for novel mutations and searching for additional genetic variants associated with susceptibility to breast and other cancers. Activating mutations in the epidermal growth factor receptor (EGFR) were identified in the Haber laboratory in the subset of non-small cell lung cancer (NSCLC) with dramatic responses to the tyrosine kinase inhibitor Gefitinib (Iressa/Tarceva).
Joel Hirschhorn, M.D., CHB Department of Medicine, Division of Genetics
(
http://www.hms.harvard.edu/dms/bbs/fac/hirschhorn.html)
Dr. Hirschhorn's laboratory focuses on using genomics to study the genetics of complex traits related to endocrinology. His research at Children's Hospital encompasses three areas: genetic studies of quantitative traits, genetic studies of type 2 diabetes and other common endocrine diseases, and development of tools and technologies to facilitate these studies.
Othon Iliopoulos, M.D. MGH Department of Medicine, Cancer Center
(
http://www.massgeneral.org/cancer/research/basic/ccr/faculty/lliopoulos.asp)
The Iliopoulos laboratory is interested in the biology of tumor suppressor genes with particular emphasis on the von Hippel-Lindau tumor suppressor protein. Lab members are currently exploring potential therapeutic implications of this known VHL-HIF interaction and, in addition, Dr. Iliopoulos and collaborators are identifying novel substrates, which are ubiquitinated by the SCFVHL E3 ligase complex. On the clinical front, lab members are creating a multidisciplinary VHL/Familial Renal Carcinoma clinic, staffed with professional genetic counselors and operating under the auspices of the MGH Cancer Genetics Program.
Isaac Kohane, M.D., Ph.D., CHB Department of Endocrinology, Informatics Program
(
http://www.childrenshospital.org/cfapps/research/data_admin/Site113/mainpageS113P0.html)
Dr. Kohane's laboratory research focuses on the development and applications of novel methodologies of bioinformatics, clinical informatics, and system biology to bring biological and clinical relevance to the intersection between genomic data acquisition modalities (e.g., expression microarrays, genome-wide haplotyping, proteomics) and clinical and biological phenotypes. The biological applications domains they are involved in include: tumorigenesis, neurodevelopment, neuro-endocrinology and transplantation biology, cardiac physiology, glucose homeostasis, and neuromuscular disease. These domain investigations include collaborations with dozens of basic biology and clinical research labs throughout Harvard and MIT. The systematic methodologies being developed and applied include: time-series analysis and signal processing, Bayesian modeling, Relevance networks, comparative genomics, and genome-wide identification of the interaction between genetic variation and functional changes in biology.
Raju Kucherlapati, Ph.D., BWH Deparment of Medicine, Division of Genetics
(
http://www.hms.harvard.edu/dms/bbs/fac/kucherlapati.html)
Dr. Kucherlapati's laboratory was involved in the mapping and sequencing of the human and mouse genomes and using yeast artificial chromosomes, and later, bacterial artificial chromosomes. Lab members made a detailed physical map of human chromosome 12. In collaboration with the Genome Center at Baylor College of Medicine, Dr. Kucherlapati's lab finished sequencing chromosome 12. They were involved in mapping and cloning several human disease genes on this chromosome, including Noonan Syndrome, Darier Diseas, Cornea Plana and Holt-Oram Syndrome. Additionally, the Kucherlapati lab is part of a consortium to sequence the mouse genome. They use their mapping and sequencing expertise to clone new human disease genes.
Louis Kunkel, Ph.D., CHB Department of Medicine, Division of Genetics
(
http://www.hms.harvard.edu/dms/bbs/fac/kunkel.html)
Dr. Kunkel's laboratory continues its two broad areas of research to address the pathogenesis and treatment of the muscular dystrophies. The first is a continuation of efforts to unravel the normal function of the dystrophin associated protein complex and why alteration of genes encoding members of the complex causes the phenotype of muscular dystrophy. The second is to develop a stem cell-based therapy for treatment of patients with muscular dystrophy. Both broad areas are driven by a hope to be curative for the muscular dystrophies.
David Kwiatkowski, M.D., Ph.D., BWH Department of Medicine, Hematology Division
(
http://www.hms.harvard.edu/dms/bbs/fac/kwiatkowski.html)
Research in the Kwiatkowski laboratory focuses broadly on the use of genetic approaches to understand human disease. One major interest is the tumor suppressor gene syndrome tuberous sclerosis. Lab members pursue studies on the human molecular genetics of this disease, develop mouse models using null and conditional alleles of TSC1 and TSC2, explore biochemical and signaling pathways, and explore therapeutic approaches. There is a particular interest in the generation of brain models of this disorder. A second major interest is the human genetics of inflammation in atherosclerosis. Lab members are pursuing a large scale whole genome scan using Affymetrix chips to identify SNPs and alleles that are associated with both inflammation and atherosclerosis risk in the Women's Health Study population.
Charles Lee, Ph.D., BWH Department of Pathology, Division of Cytogenetics
(
http://www.fish-chromosome.net/)
The Lee Laboratory is involved in the development, assessment, and application of emerging molecular cytogenetic technologies in basic and translational-based research. Techniques employed include multicolor karyotyping, color banding (Rx-FISH), and comparative genomic hybridization (CGH) to identify and characterize specific chromosomal imbalances in human development and congenital disorders as well as study the chromosomal mechanisms of tumorigenesis in humans and other model organisms. The three major projects that are ongoing in the research laboratory are: (1) Development and application of molecular cytogenetic tools for the zebrafish, (2) Biomarkers in neoplastic disorders, and (3) Copy Number Variations in mammalian genomes.
David Louis, M.D., MGH Department of Pathology, Cancer Center
(
http://www.massgeneral.org/cancer/research/basic/ccr/faculty/louis.asp)
Dr. Louis' laboratory studies the molecular genetic basis of human brain tumors, both common sporadic brain tumors as well as rarer, inherited brain tumor syndromes. Most of the work has focused on malignant gliomas. The laboratory was the first to demonstrate that molecular genetic analysis could be used to divide glioblastomas into clinicopathologically distinct genetic subsets. The laboratory has also shown that specific genetic alterations are powerful predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. Recent work has focused on the effects of chemotherapy on malignant glioma genotype at the time of recurrence.
Marcy MacDonald, Ph.D., MGH Department of Neurology, Center for Human Genetic Research
(
http://www.hms.harvard.edu/dms/bbs/fac/macdonald.html)
Dr. MacDonald's laboratory focuses on inherited diseases of the nervous system, utilizing the genetics research paradigm. Dr. MacDonald and her colleagues have used genotype-phenotype studies to discover gene mutations that cause Huntington's disease, Neuronal Ceroid Lipofuscinosis, Benign Hereditary Chorea, and other disorders, and her group has pioneered the use of genetic knock-in mouse models that precisely replicate the human disease mutations, to delineate critical early steps in pathogenesis. Genetic studies in Huntington's disease and Neuronal Ceroid Lipofuscinosis, in humans and mice, aim to reveal genes that modify the onset of early disease events, providing validated targets for the development of effective interventions.
Richard Maas, M.D., Ph.D., BWH Department of Medicine, Division of Genetics
(
http://www.hms.harvard.edu/dms/bbs/fac/maas.html)
Work in the Maas laboratory focuses on the developing mammalian eye as a model system for understanding organogenesis. Across Metazoa, the Pax6 gene resides high in the genetic regulatory hierachy controlling eye formation. Using naturally occurring mouse mutants and knockout mice that lack the function of Pax6, Msx, Eya and other genes implicated in eye development, the actions of these genes has begun to be ordered into a regulatory pathway. A multidisciplinary approach has been taken to this problem, including the application of experimental embryology, molecular biology and biochemistry, and human and mouse genetics. An exciting theme emerging from this work is that the genetic regulatory pathways controlling eye development are not only evolutionary conserved, but are also utilized in the genesis of different mammalian organs besides the eye.
Cynthia Morton, Ph.D., BWH Departments of Obstetrics, Gynecology and Reproductive Biology and Pathology, Division of Cytogenetics
(
http://www.hms.harvard.edu/dms/bbs/fac/morton.html)
An overall theme of research projects in human genetics in Dr. Morton's laboratory is to apply evolving techniques in molecular cytogenetics to address problems in human cytogenetics; interests include chromosomal rearrangements in inherited and acquired cytogenetic disorders. A major effort is underway to isolate genes involved in uterine leiomyomata, common pelvic tumors in women that are the most frequent indication for hysterectomy in the United States (www.fibroids.net). Another primary interest in Dr. Morton's laboratory is to identify genes involved in hearing and deafness disorders (hearing.bwh.harvard.edu). Lastly, a gene discovery effort known as DGAP (Developmental Genome Anatomy Project) (dgap.harvard.edu) is in progress to identify and characterize genes critical in human development from balanced chromosomal aberrations present in individuals with multiple congenital anomalies.
Ellis Neufeld, M.D., Ph.D., CHB Department of Medicine, Division of Hematology/Oncology
(
http://www.childrenshospital.org/cfapps/research/data_admin/Site138/mainpageS138P0.html)
Dr. Neufeld's basic research focuses on thiamine-responsive megaloblastic anemia (TRMA) syndrome, a rare inherited early-onset disorder that leads to anemia, diabetes, and progressive deafness, but can be ameliorated with high doses of thiamine (vitamin B1). The Neufeld lab has demonstrated that while normal cells can accumulate thiamine from their environment at very low concentrations, TRMA cells cannot. Moreover, TRMA cells grown in the laboratory die in the absence of thiamine. Dr. Neufeld and colleagues have subsequently identified the gene responsible for TRMA as a high-affinity thiamine transporter, and are now investigating how the transporter causes defects in the bone marrow, in glucose regulation, and in hearing.
Stuart Orkin, M.D., CHB Department of Pediatric Oncology
(
http://www.hms.harvard.edu/dms/bbs/fac/orkin.html)
Dr. Orkin's laboratory studies the development of the hematopoietic system, the biology of hematopoietic stem cells, and the interface between normal and leukemic hematopoiesis. Approaches include conventional molecular biology and contemporary methods of mouse genetics.
Norbert Perrimon, Ph.D., HMS Department of Genetics
(
http://www.hms.harvard.edu/dms/bbs/fac/perrimon.html)
Dr. Perrimon's laboratory is interested in identifying components involved in signal transduction pathways that mediate the interaction between cells, as well as pathways involved in morphogenesis using Drosophila as a model system. To identify components of specific pathways, a high-throughput methodology has been devised in 384 well plates that allow the quick identification of all genes involved in a specific cell-based process. The method is based on the mechanism of RNA interference that has proven highly specific and efficient. Dr. Perrimon's approach is to use these screens to identify the genes involved in a cell-based assay first, and then return to the organism to validate the candidate genes.
Martin Pollak, M.D., BWH Department of Medicine
(
http://www.fsgs.bwh.harvard.edu/)
Dr. Pollak's laboratory is interested in identifying genes involved in the development of focal segmental glomerulosclerosis (FSGS). FSGS is a common form of renal disease, seen both as an isolated entity and as a consequence of HIV infection, diabetes, obesity, and hypertension. Because FSGS is also a cause of renal dysfunction secondary to multiple other diseases, the Pollak laboratory is examining the role of this FSGS gene as a candidate renal dysfunction susceptibility gene. Current efforts are underway to understand the function of ACTN4 and the mechanism of this form of kidney disease using mouse models and cell biologic approaches. The Pollak laboratory is also working to identify additional human FSGS genes.
Heidi Rehm, Ph.D., BWH Department of Pathology, Laboratory for Molecular Medicine (
(
http://www.hpcgg.org/Faculty/rehm.jsp)
The main areas of Dr. Rehms's research include studies of: 1) Norrie disease; 2) genotype/phenotype studies in hereditary hearing loss; 3) access to and quality of genetics services for hereditary hearing loss; and 4) the development of molecular diagnostic tools for identifying genetic causes of hearing loss.
Christine Seidman, M.D., BWH Department of Medicine, Division of Genetics
(
http://www.hms.harvard.edu/dms/bbs/fac/seidman_christine.html)
The Seidman laboratory harnesses and integrates clinical medicine and molecular technologies to define disease-causing gene mutations and genetic variations that increase disease risk. The laboratory also develops and interrogates genetically engineered models to elucidate pathogenetic mechanisms for human disease. Major research projects focus on discovery of the genetic contributions to cardiovascular disease (including dilated and hypertrophic cardiomyopathy, coronary artery disease and congenital heart disease), hearing loss, and lymphedema.
Jonathan Seidman, Ph.D., HMS Department of Genetics
(
http://www.hms.harvard.edu/dms/bbs/fac/seidman_jonathan.html)
The central focus of Dr. Seidman's laboratory is to identify human gene mutations that cause heritable disorders involving cardiac structure, function and development. Investigations over the past five years have helped to understand the molecular basis of several different inherited disorders: familial hypertrophic cardiomyopathy, familial dilated cardiomyopathy, Holt-Oram syndrome (congenital defects of heart and hand), and familial atrial septal defect. Genetically engineered mice are available to create mouse models of some of these conditions. Analyses of these mice provide insights into the roles of specific genes in the disease process.
Philip Sharp, Ph.D., MIT Department of Biology, The McGovern Institute
(
http://web.mit.edu/sharplab/index.html)
Investigation into the mechanisms responsible for the activities of short interfering RNAs (siRNAs) are ongoing in the Sharp Laboratory with the objective of increasing their effectiveness in gene silencing. Sharp lab members are also investigating the roles of short RNAs in transcriptional silencing in murine embryonic stem cells. siRNAs have overlapping functions with microRNAs, endogenous genes in mammalian cells that, when paired by partial complementarity to an mRNA, inhibit accumulation of the corresponding protein. The Sharp Laboratory is studying this translational repression and is also using RNAi technology to identify specific proteins important for the regulation of alternative RNA splicing and transcription.
Susan Slaugenhaupt, Ph.D., MGH Department of Neurology, Center for Human Genetic Research
(
http://www.hms.harvard.edu/dms/bbs/fac/Slaugenhaupt.html)
The overall goal of the Slaugenhaupt lab is to bring the study of genetic disease full circle: from the initial collection of family data, to the cloning and characterization of the culprit gene, and back to the patient via development of improved diagnostics and effective therapies. The work in the lab is currently focused on two neurological disorders, familial dysautonomia and mucolipidosis type IV, and the common cardiac disorder mitral valve prolapse.
Shamil Sunyaev, Ph.D., BWH Department of Medicine, Division of Genetics
(
http://www.hms.harvard.edu/dms/bbs/fac/sunyaev.html)
The Sunyaev laboratory is a computational biology laboratory. They develop and apply computational methods to pursue various problems in fields of genetics, genomics and proteomics. The main interest of Dr. Sunyaev's laboratory is to analyze the population genetic variation and the genome divergence between species with the major focus on the protein coding regions. The effect of amino acid substitutions on function and structure of proteins can be frequently understood and even predicted via comparative sequence analysis and analysis of the protein structure. Lab members relate the above functional studies to the evolutionary process of natural selection to track the evolution of proteins at the molecular level. Results of structural and evolutionary studies can be further applied to the data on human genetic polymorphisms with the goal to understand the complex mechanisms of inheritance and most importantly the genetic basis of human multifactorial diseases.
Sapna Syngal, M.D., M.P.H., DFCI Department of Medical Oncology/Population Sciences
(
http://www.dfhcc.harvard.edu/membership/member-profile/member/383/0/)
Dr. Syngal's research is devoted to the study of genetics, screening and primary prevention of gastrointestinal tumors, primarily colorectal cancer. The major focus is on hereditary colorectal cancer syndromes, notably hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP). Lab members are seeking to characterize the genetic causes of cancer susceptibility in such families, and they have tested over a hundred families for mutations in the mismatch repair genes MSH2, MLH1 and MSH6. Dr. Syngal's laboratory is also conducting a study of the prevalence of the I1307K APC mutation in individuals with sporadic colorectal polyps and carcinomas. Other ongoing projects include chemoprevention trials in patients with familial polyposis as well as sporadic colorectal polyps, and studies of compliance with screening in groups at high and moderate risk for the development of GI cancers.
Clifford Tabin, Ph.D., HMS Department of Genetics
(
http://www.hms.harvard.edu/dms/bbs/fac/tabin.html)
Dr. Tabin's research involves the genetic basis by which form and structure are regulated during vertebrate development. Classical methods of experimental embryology are combined with modern molecular and genetic techniques for regulating gene expression during embryogenesis. One of the classic systems for the study of embryonic development is the chick embryo, where grafting experiments have given profound insight into such questions as the patterning of developing limb axes, and the control of organogenesis. These classical experiments provide a context for interpreting modern molecular studies and the methods they employed also give an additional set of tools for manipulating the embryo. Important complementary information is gained from studies taking advantage of the powerful techniques for regulated misexpression and gene deletion in the mouse.
Daniel Tenen, M.D., BIDMC Department of Medicine, Division of Hematology/Oncology
(
http://www.hms.harvard.edu/dms/immunology/fac/Tenen.html)
The Tenen laboratory is interested in isolating and characterizing factors which play a role in the differentiation of hematopoietic stem cells into different specific lineages, with particular focus on myeloid (granulocyte and monocyte) differentiation in normal and leukemic cells. Current studies are focused on two master transcription factors which are regulators of myeloid development: the Ets factor PU.1, and C/EBP alpha. Current efforts in the laboratory focus on understanding regulation, signal transduction pathways, and interacting partners of PU.1 and C/EBP alpha. Other projects directed at leukemogenic mechanisms include models of murine leukemia using inducible expression of translocation fusion proteins, such as the Bcr-Abl protein. Long term goals are to understand the abnormalities seen in acute myelogenous leukemia (AML), in which differentiation of myeloid blasts is blocked, and to use these myeloid promoters as tools to drive lineage and stage specific expression of heterologous genes in recipient ES cells and transgenic mice, as a step toward gene therapy applications.
Christopher Walsh, M.D., Ph.D., CHB Division of Genetics and BIDMC Department of Neurology
(
http://www.hms.harvard.edu/dms/bbs/fac/walsh_ChrisA.html)
The Walsh laboratory is interested in cellular and genetic mechanisms of development of the cerebral cortex. The cortex is a good system for studying neuronal development, since there are known mutations that systematically disrupt its development. Abnormal development of the cerebral cortex in humans results in epilepsy, autism, mental retardation, dyslexia, and other learning disorders, and perhaps some psychiatric conditions as well. Several projects are directed at trying to understand the basic biology of the cortex by studying the mutations that disturb its development.
Scott Weiss, M.D., Ph.D., BWH Department of Medicine, Channing Laboratory
(
http://www.channing.harvard.edu/weiss.htm)
Dr. Weiss' laboratory focuses on risk factors and natural history of asthma and chronic obstructive pulmonary disease (COPD). Because of the importance of pregnancy and early life factors for the development of asthma and COPD, lab members have developed a series of birth cohort studies to assess environmental and genetic risk factors for asthma. A current research focus is on the effect of maternal diet, specifically N-3 and N-6 fatty acid intake, their influence on immune system function, and on the development of asthma in early life. An additional project that relates to environmental risk factors and the natural history of asthma is the Childhood Asthma Management Program (CAMP). The CAMP project is a multi-center randomized control trial of the effect of nedocromil and budesonide as anti-inflammatory control therapy on the long-term growth and development of children with asthma.
Clinical Training Mentors
Gerard Berry, M.D., CHB Department of Medicine, Division of Genetics
Dr. Berry was recently hired as the new Director of the Metabolic Program at CHB. His area of expertise is inherited metabolic disease. He will become Co-Director of the HMS ABMG Clinical Biochemical Genetics Program.
Frederick Bieber, Ph.D., BWH Department of Pathology
Dr. Bieber is the Co-Director of the HMS ABMG Clinical Molecular Genetics Program and teaches in the Advanced Human Genetics course. His areas of expertise are cytogenetics, fetal and forensic pathology.
Marsha Browning, M.D., M.P.H., MGH Department of Pediatrics, Center for Human Genetic Research
Dr. Browning is an attending physician at MGH, and is conducting research in the laboratory of Dr. Susan Slaugenhaupt on mucolipidosis type IV. She is a 2005 graduate of the HMS ABMG Training Program.
Deyanira Corzo, M.D., CHB Department of Medicine, Division of Genetics
Dr. Corzo is an attending physician at CHB. She is interested in clinical studies for treatment of lysosomal storage diseases.
Gerald Cox, M.D., CHB Department of Medicine, Division of Genetics
Dr. Cox is an attending physician at CHB. His interests are in enzyme replacement therapy for lysosomal storage diseases. His other interests include genetic causes of cardiomyopathy, velo-cardio-facial syndrome, and Bardet-Biedl syndrome.
Paola Dal Cin, Ph.D., BWH Department of Pathology, Division of Cytogenetics
Dr. Dal Cin is a staff cytogeneticist at BWH with a special interest in cancer cytogenetics. She teaches in the Advanced Human Genetics course and supervises Clinical Genetics and Cytogenetics trainees during their clinical rotations.
Christine Finn, M.D., MGH Department of Psychiatry
Dr. Finn supervises trainees in the clinics at BWH and MGH. In addition, she teaches in the Advanced Human Genetics course. She is conducting research on genotype-phenotype correlations in velo-cardio-facial syndrome in conjunction with Dr. Raju Kucherlapati and will be co-mentoring a research trainee with him.
Natasha Frank, M.D., CHB Department of Medicine, Division of Genetics
Dr. Frank is a staff physician at BWH/MGH and researcher at CHB. Dr. Frank supervises trainees in the BWH and MGH clinics. She also teaches in the Advanced Human Genetics course. Her research is focused on the myoregenerative potential of ABCB5+ progenitors.
Anne Giersch, Ph.D., BWH Department of Pathology, Division of Cytogenetics
Dr. Giersch is a staff cytogeneticist at BWH. She teaches in the Advanced Human Genetics course and supervises Clinical Genetics and Cytogenetics trainees during their clinical rotations. Her primary research effort is in hereditary deafness and her current focus is on the development and application of an inner ear cDNA microarray.
Patricia Greenstein, M.D., BIDMC Department of Neurology
Dr. Greenstein teaches genetics in the HMS course which trainees are encouraged to attend. Dr. Greenstein's research interests are in clinical neurogenetics and the ataxias.
David Harris, M.D., CHB Department of Medicine, Division of Genetics
Dr. Harris is an attending physician at CHB. He supervises trainees in the genetics clinic there. In addition, he coordinates and moderates "Ethics Talks" at Genetics Walk Rounds and he teaches in the Advanced Human Genetics course. He also serves as the clinical geneticist on the Developmental Genome Anatomy Project (DGAP, dgap.harvard.edu) research project described below.
Anne Higgins, Ph.D., BWH Department of Pathology, Division of Cytogenetics
Dr. Higgins is a staff cytogeneticist at BWH. She teaches in the Advanced Human Genetics course and supervises Clinical Genetics and Cytogenetics trainees during their clinical rotations. Dr. Higgins was supported by this T32, and her primary research is in the Developmental Genome Anatomy Project (DGAP, dgap.harvard.edu) research project described below.
Ingrid Holm, M.D., CHB Department of Medicine, Division of Genetics
Dr. Holm is an attending physician at CHB. She supervises trainees in the inpatient and outpatient clinics at CHB. She also serves as an instructor in the Advanced Human Genetics course. Her research interests are in genetic endocrine and skeletal disorders.
Lewis Holmes, MGH Department of Pediatrics, Division of Genetics and Teratology
Dr. Holmes is Director of the Prenatal Diagnosis Program at MGH and supervises trainees in the Prenatal Clinic. Dr. Holmes is currently involved in several clinical research projects, including interrelationships between environmental exposures and susceptibility genes.
Mira Irons, M.D., CHB Department of Medicine, Division of Genetics
Dr. Irons is Program Director for the HMS ABMG Training Program. She also teaches in the Advanced Human Genetics course. Dr. Irons' research focus is on neurofibromatosis and Smith Lemli-Optiz syndrome.
Victoria Joshi, Ph.D., MGH Department of Pathology, Laboratory for Molecular Medicine
Dr. Joshi supervises HMS AMBG trainees during their rotations in the Laboratory for Molecular Medicine. She also teaches in the Advanced Human Genetics course.
Olivier Kocher, M.D., Ph.D., BIDMC Department of Pathology
Dr. Kocher supervises Molecular Genetic Pathology fellows during rotations at BIDMC. His research focuses on cloning and characterization of novel molecules playing a role in oncogenesis to define new markers for malignant cell populations and also to better understand tumor biology.
Harvey Levy, M.D., CHB Department of Medicine, Division of Genetics
Dr. Levy is Co-Director of the HMS ABMG Clinical Biochemical Genetics Program, teaches in the Advanced Human Genetics course, and supervises fellows during their clinical rotations. His interests involve clinical research in inborn errors of metabolism.
Azra Ligon, Ph.D., BWH Department of Pathology, Division of Cytogenetics
Dr. Ligon is a staff cytogeneticist at BWH. She serves as the Director of the HMS ABMG Program in Cytogenetics, teaches in the Advanced Human Genetics course and supervises Clinical Genetics and Cytogenetics trainees during their clinical rotations.
Angela Lin, M.D., MGH Department of Pediatrics, Division of Genetics and Teratology
Dr. Lin supervises trainees in the genetics clinics at MGH. She also conducts research studying risk factors and prevalence of birth defects, especially congenital heart disease.
Neal Lindeman, M.D., BWH Department of Pathology, Division of Molecular Diagnostics
Dr. Lindeman supervises Molecular Genetic Pathology fellows in clinical rotations and teaches in the Advanced Human Genetics course. His research focuses on EGFR response to lung cancer.
Janina Longtine, M.D., BWH Department of Pathology, Division of Molecular Diagnostics
Dr. Longtine is a Molecular Genetic Pathologist. She serves as the Director of the HMS Molecular Genetic Pathology Training Program (
http://www.brighamandwomens.org/pathology/Medical/MolecGeneticPathology.aspx). She is also the Director of the BWH Molecular Diagnostics Laboratory, and thus supervises students during their clinical rotations there. In addition, she teaches in the Advanced Human Genetics course.
Helen Lyon, M.D., M.P.H., CHB Department of Medicine, Division of Genetics
Dr. Lyon is an attending physician at CHB who supervises fellows in the genetics clinics there. She also teaches in the Advanced Human Genetics course. Her area of interest is the genetics of Congenital Heart Disease.
David Miller, M.D., Ph.D., CHB Department of Medicine, Division of Genetics
Dr. Miller supervises trainees during rotations in the CHB Genetics DNA Diagnostic Lab and in the genetics clinics at CHB. He also teaches in the Advanced Human Genetics course. Dr. Miller's area of research interest is the genetics of inflammation in atherosclerosis.
Michael Murray, M.D., BWH Department of Medicine, Division of Genetics
Dr. Murray is the Director of the BWH clinical genetics rotation. He is also the Director of the BWH Genetics Medicine Residency Program. He supervises trainees in clinics and teaches in the Advanced Human Genetics course. His area of interest is the genetics of infectious and connective tissue disease. Dr. Murray has developed and led the Brigham and Women's Family History Project (brighamandwomens.org/familyhistory/) and also developed an annual continuing education course, The Genetics of Adult Medicine, now in its second year (
http://cme.med.harvard.edu/cmeups/custom/00261416/TheGeneticBasisofAdultMedicine.htm).
Edward Neilan, M.D., Ph.D., CHB Department of Medicine, Division of Genetics
Dr. Neilan is a clinical and biochemical geneticist who is an attending physician at CHB. He supervises trainees in the clinics and in the biochemical genetics laboratory at CHB. He also teaches in the Advanced Human Genetics course. His area of research interest is Cockayne syndrome.
Jonathan Picker, M.D., Ph.D., CHB Department of Pediatrics
Dr. Picker supervises trainees at CHB and teaches in the Advanced Human Genetics course. His research interests are in the genetics of schizophrenia.
Barbara Pober, M.D., MGH Department of Pediatrics, Division of Genetics and Teratology
Dr. Pober supervises trainees at MGH and teaches in the Advanced Human Genetics course. Her clinical interests include Williams syndrome, congenital diaphragmatic hernia, and the genetic basis for birth defects.
Amy Roberts, M.D., CHB Department of Medicine, Division of Genetics
Dr. Roberts is the Director of the CHB clinical genetics rotation and supervises trainees in the clinics there. She also teaches in the Advanced Human Genetics course. She is conducting research on genotype-phenotype correlations in Noonan syndrome.
Joaquin Santolaya, M.D., BWH Department of Obstetrics, Gynecology and Reproductive Biology
Dr. Santolaya recently joined the Center for Fetal Medicine at BWH and supervises trainees in the antenatal diagnostic clinic there.
Vivian Shih, M.D., MGH Department of Neurology
Dr. Shih is the Director of the MGH Amino Acid Disorders Laboratory and supervises trainees there. Her current research interests include disorders involving homocysteine metabolism, hyperammonenic syndromes, other amino and organic acid disorders, and fatty acid oxidation defects.
Katherine Sims, M.D., MGH Department of Neurology, Neurogenetics DNA Diagnostic Laboratory
Dr. Sims is the Director of the MGH Neurogenetics DNA Diagnostics Laboratory and supervises trainees during their clinical rotations in that lab. Her research interests include primary mitochondrial disorders, lysosomal storage disorders - diagnosis, medical assessment, management and treatment, neurogenetic disorders and issues of diagnosis, management and genetic information transfer, and Norrie disease.
Joan Stoler, M.D., MGH Department of Pediatrics, Division of Genetics and Teratology
Dr. Stoler is the Director of the MGH clinical genetics rotation and supervises trainees during their rotation there. She also teaches in the Advanced Human Genetics course. Her particular area of interest is in connective tissue disorders.
Peter Tishler, M.D., BWH Department of Medicine, Division of Genetics
Dr. Tishler supervises trainees is the BWH General Genetics Clinic. Dr. Tishler's interests include the genetics of sleep apnea syndrome and metabolic disease.
Stanislawa Weremowicz, Ph.D., BWH Department of Pathology, Division of Cytogenetics
Dr. Weremowicz is a staff cytogeneticist at BWH. She supervises Clinical Genetics and Cytogenetics trainees during their clinical rotations.
Louise Wilkins-Haug, M.D., Ph.D., BWH Department of Obstetrics, Gynecology and Reproductive Biology
Dr. Wilkins-Haug supervises trainees in the Center for Fetal Medicine at BWH. She also teaches in the Advanced Human Genetics course. Dr. Wilkins-Haug's research has focused on the genetic basis of intrauterine fetal growth restriction, specifically abnormal placental karyotypes with a chromosomally normal fetus, confined placental mosaicism.
Bai-lin Wu, Ph.D., CHB Department of Laboratory Medicine
Dr. Wu is a molecular geneticist whose primary responsibilities focus on the direction of the CHB Genetics Diagnostic Laboratory. As such, he supervises trainees in the HMS ABMG Training Program during rotations in that laboratory.
Sheng Xiao, M.D., BWH Department of Pathology, Division of Cytogenetics
Dr. Xiao is a staff cytogeneticist at BWH. He supervises Clinical Genetics and Cytogenetics trainees during their clinical rotations.
