Research interests within the Division span many areas both within contemporary genetics and throughout biomedicine. Over time, the Genetics Division has blossomed into a powerful synergistic hub for interdisciplinary research; this is illustrated by the diversity of research interests within the division. For example, many Genetics Division faculty share co-appointments in other BWH Divisions, including Rheumatology, Renal Medicine, Cardiovascular Medicine, Gastroenterology, Pulmonary Medicine, Preventive Medicine and Allergy, and also in other BWH and HMS Departments. This creates a rich environment for interdisciplinary research on a wide range of topics, with most of our faculty physically located in the HMS New Research Building. Areas of active investigation include genome science and gene editing; bioinformatics; computational genetics and data science; human genetics (including Mendelian and complex disease genetics and human genetic variation); immunobiology and autoimmune diseases, developmental and cancer genetics; gene therapy; chemical biology; proteomics and metabolomics; transcription factors; vascular biology and disease; myogenesis and neuromuscular disorders; renal disease, corneal and stem cell biology; aging; and redox biology.
Computational Genetics, Genomics, and Data Sciences
Genome Analysis Tools and Genomic Analysis of Autoimmunity
Dr. Soumya Raychaudhuri’s research group uses genetics, genomics, and data science to understand autoimmune diseases. In addition to his own work, which focuses heavily on aspects of rheumatoid arthritis (RA), Dr. Raychaudhuri, a co-appointed member of the Division of Rheumatology, leads the BWH Center for Data Sciences that includes other talented Genetics Division faculty. These include Dr. Ilya Korsunsky, who is developing and applying methods for spatial transcriptomics with a special emphasis on RA and other autoimmune diseases. Another Division faculty member, Dr. Po-Ru Loh, develops and applies new computational tools to solve statistical challenges in quantitative genetics. Dr. Loh’s group investigates copy-number variants (CNVs) and variable number tandem repeats (VNTRs) and their impact on human traits and disease risk.
Immunogenetics and the Antibody Responses in Allergy and COVID-19 Infection
Dr. Duane Wesemann, a co-appointed member of the Division of Allergy, uses mouse genetics, human studies, cellular biology, single-cell transcriptomics, and computation to elucidate the underlying features and elasticity of antibody recognition capacity. His lab along with that of Dr. Steve Elledge has also been at the forefront in elucidating immune response to Covid19 infection and Covid19 vaccines.
Analysis of Human Genetic Variation
Dr. Shamil Sunyaev, also a member of the HMS Dept. of Biomedical Informatics (DBMI) and his computational team are focused on the analysis of human genetic variation as evident from large-scale sequencing data sets and on developing new algorithms for identifying both coding and non-coding DNA sequence variants.
Statistical Genetics of Mendelian Disorders
Dr. Christopher Cassa and his research group study the statistical genetics of Mendelian disorders. Dr. Cassa’s group has made significant progress on a model to estimate clinical risk that is attributable to both monogenic and polygenic variation.
Genomic Medicine, Developmental Genetics and Regenerative Medicine
Gene Discovery in Human Disease
Dr. Richard Maas participates in several gene discovery projects aimed at identifying disease-causing genes in individuals with undiagnosed disease. These include the Harvard/BWH Undiagnosed Disease Network Clinical Site and Brigham Genomic Medicine (BGM). Both initiatives apply WES/WGS and RNA-seq to patients with challenging undiagnosed genetic disease. Another effort, founded and directed by Dr. Alireza Haghighi in the Genetics Division is a new HMS International Center for Genetic Disease (iCGD). It focuses on using WGS and genomic medicine to identify disease-causing genes indigenous to parts of the world such as the Middle East where recessive genetic diseases are a matter of public health. Another Division faculty member, Dr. Arezou Ghazani, focuses on the interaction between germline cancer genotypes and cancer somatic variants. Drs. Haghighi and Ghazani are currently pursuing genomic contributions to diseases in the Middle East and in Croatia, respectively.
Extending Genomic Medicine to Clinical Practice
Dr. Robert Green and his Genomes2People Research Program (G2P) focus on the implementation of genomic medicine into routine clinical care. Their team is currently especially interested in understanding genetic risk in newborns.
Neuromuscular Disease
Dr. Vandana Gupta’s laboratory is focused on genetics and therapeutic developments in neuromuscular diseases. Dr. Gupta has identified a number of disease-causing genes in neuromuscular disorders by working at the intersection of human genetics and model organisms.
Liver Development, Regeneration, and Carcinogenesis
Dr. Wolfram Goessling, co-appointed in MGH Gastroenterology, and his group focus on understanding the signals that indicate liver injury and that regulate growth and regeneration. His laboratory investigates both zebrafish and mouse models to discover novel regulatory pathways of liver development and to evaluate their importance for recovery after toxic and physical injury.
ABCB5 Stem Cells in Ocular Development and Repair
Dr. Natasha Frank is a medical geneticist whose laboratory research explores the biology of stem cells and their roles in physiologic organogenesis, repair, and malignant transformation, with the goal of developing novel stem cell-targeted strategies in the fields of tissue regeneration and cancer.
Imaging Mass Spectrometry
The BWH Center for NanoImaging maintains a modern CAMECA nanoSIMS 50L instrument, as well as a staff consisting of instrument operator and center director Dr. Christelle Guillermier. This technology is applied collaboratively to image a range of isotopically tagged biomolecules molecules and pharmaceuticals with subcellular resolution.
Mechanisms of Vascular Disease
The research of Dr. Raj Gupta, who holds appointments in both the Divisions of Genetics and of Cardiovascular Medicine, focuses on the connection between genetic variation and cellular phenotypes for vascular disease. For example, his recent work indicates a convergence of coronary artery disease genes onto endothelial cell programs.
Kidney Disease Mechanisms
Dr. Anna Greka, also a member of the Division of Renal Medicine, is investigating molecular mechanisms of renal disease with particular interest in membrane proteins and transport and an orientation toward novel therapeutics. In one body of work, she investigated the molecular mechanisms of a toxic proteinopathy, MUC1-related kidney disease, and tied this to MUC1 sequestration by TMED9 cargo receptor-containing vesicles of the early secretory pathway.
Genomic Technologies and the Study of Gene Regulation
Genome Editing Applied to Gene Regulation and Human Disease
Dr. Richard Sherwood uses high-throughput CRISPR/Cas9 gene-editing screening combined with machine learning to understand and develop new treatments for genetic disease. His group is also developing new experimental and computational methods to analyze genomes and chromatin.
Regulation of Gene Expression
Dr. Mitzi Kuroda studies how chromatin organization governs the fidelity of gene expression patterns during development. Her laboratory employs genetics, genomics, and biochemistry to study epigenetic regulation in the fruit fly (Drosophila) and in mammalian cells in culture.
Genomic Approaches to Understanding Transcriptional Regulation
Dr. Martha Bulyk’s lab continues their pioneering work in the development of new experimental technologies and computational genomic methods for deciphering how gene regulatory codes are encoded in the genome, read out by regulatory factors in cells, and impacted by genetic variation.
Cancer Genetics and Therapeutics
Innovative Genetic Technologies and Cancer
Dr. Stephen Elledge’s laboratory works in cancer research with a special emphasis on the role of the immune system and tumor immune surveillance. One recent highlight from the Elledge laboratory uses T-Scan II, a highly sensitive genome-scale CD4+ antigen discovery platform, to identify epitopes for CD4 T cells. T-Scan II integrates endogenous HLA-II antigen-processing machinery in synthetic antigen-presenting cells and TCR signaling in T cells to enable simultaneous screening of multiple HLAs and TCRs. By leveraging genome-scale human, virome, and epitope mutagenesis libraries, TScan-II facilitates de novo antigen discovery and exploration of TCR specificity.
Cancer therapies, cell signaling, and epigenetics
The focus of the Cichowski laboratory is to elucidate mechanisms that drive human cancer, identify novel therapeutic targets, and use robust animal models to test promising therapies. Specifically, they have been investigating how specific signaling and epigenetic pathways converge and have been using this insight to develop novel combination therapies.
Epithelial Cancer Cells of Origin
Dr. Zhe Li and his laboratory are focused on understanding how cancer cells evolve from their normal target cells (i.e., cells of origin) through the accumulation of genetic mutations and epigenetic changes, and through interaction with the microenvironment (e.g., immune cells), as an avenue for identifying unique pathways. Dr. Sahar Nissim, co-appointed in the Division of Gastroenterology, and his laboratory uses single cell transcriptomics and human genetics to focus on the causal cellular, molecular and epigenetic mechanisms of pancreatic cancer development and on the pursuit of novel therapies.
Biochemical and Chemical Biology Investigation
Redox Biology and Aging
Dr. Vadim Gladyshev’s research focuses on redox biology, uncovering the molecular basis for changes in longevity by identifying the genetic and biochemical basis for adaptations in long-lived mammals, and examining longevity-associated processes across all mammals. Understanding the mechanisms of aging – and potentially delaying the aging process – may allow the delay in the onset of diseases such as cancer, diabetes, and Alzheimer’s disease. The Gladyshev laboratory develops biomarkers of aging, including DNA methylation clocks, and studies mechanisms of age-related deleterious processes.
Chemical Biology
Dr. Phil Cole’s laboratory studies the chemical biology of protein post-translational modifications (PTMs) in the context of signaling, epigenetics, and cancer. His laboratory develops and applies chemical approaches including protein semi-synthesis and small molecule probes to protein phosphorylation, acetylation, ubiquitination, and other PTMs in enzymes and cellular networks.