Protein Synthesis, Degradation, and Homeostasis

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Amy Lee

Assistant Professor of Cell Biology
Assistant Professor of Cancer Immunology and Virology (DFCI)

Amy S.Y. Lee Ph.D. received her Ph.D. in Virology at Harvard University in 2012, and then performed postdoctoral research on biochemical and cellular mechanisms of gene regulation at University of California – Berkeley. She joined the faculty in the Department of Biology at Brandeis University in 2016, and subsequently moved to join Harvard Medical School and DFCI in 2020. 

The Lee Lab studies how cells sense and respond to environmental signals by modulating protein synthesis. Specifically, the lab’s research is focused on discovering mechanisms regulating specialized mRNA translation and how these pathways are controlled during organismal development, viral infection, and cellular stress. To obtain broad insights into regulation of protein synthesis, the Lee lab applies an integrative approach combining RNA-protein biochemistry, cell-based experiments, structural biology, and development of new sequencing-based technology. Our research provides mechanistic understanding of the translation regulation networks that coordinate the precise control required for correct development and cellular function.

Wade Harper

Chair & Professor of Cell Biology
Bert and Natalie Vallee Professor of Molecular Pathology

Wade Harper, Ph.D., is the B and N Vallee Professor of Molecular Pathology, a Professor of Cell Biology, and the Chair of Cell Biology in the Blavatnik Institute at Harvard Medical School. He received his Ph.D. in Chemistry from Georgia Institute of Technology, prior to performing post-doctoral work in protein biochemistry of growth factors at Harvard Medical School. He joined the faculty in the Department of Biochemistry and Molecular Biology at Baylor College of Medicine in 1988 and subsequently moved to the Department of Pathology at Harvard Medical School (in 2003) and to the Department of Cell Biology in 2011.

The Harper Lab studies mechanisms underlying cellular homeostasis and signaling, with a focus on the ubiquitin system and the autophagy-lysosome system. The interest in the ubiquitin-proteasome system in the Harper Lab initially emerged through studies to understand how cell cycle regulators (cyclins and CDK inhibitors) are degraded to control cell cycle transitions, resulting in the discovery of cullin-RING ubiquitin ligases, and their roles in phosphorylation-dependent protein degradation. The Harper Lab currently uses quantitative proteomics, imaging, and biochemical approaches to elucidate underlying biochemical mechanisms controlling protein turnover, and applies these approaches to examine regulatory pathways relevant to various neurodegenerative disease, including Parkinson’s and Alzheimer’s diseases. A major focus currently is the PARKIN ubiquitin ligase, which controls turnover of damaged mitochondria via the autophagy pathway and is mutated in Parkinson’s Disease. The Harper Lab, together with the Gygi Lab at HMS, is also using proteomics to develop a large-scale human protein interaction network including the majority of proteins encoded by the human genome.

Randall King

Harry C. McKenzie Professor of Cell Biology

Randy King, M.D., Ph.D. was appointed to the faculty in 2000, after three years as the first Institute Fellow of the Institute of Chemistry of Cell Biology at Harvard. He received his undergraduate degree from Carleton College, followed by a Ph.D. in Biochemistry from UCSF, where he co-discovered the Anaphase-Promoting complex/Cyclosome (APC), and M.D. from Harvard Medical School. He was named the Harry C. McKenzie Professor of Cell Biology in 2013 and has received numerous awards in recognition of his contributions to medical education.

The King lab integrates chemical and cell biological approaches to study cell division and chromosome segregation.

Sichen (Susan) Shao

Assistant Professor of Cell Biology

Sichen (Susan) Shao, Ph.D., joined Harvard Medical School in 2016. Susan received her Ph.D. in biological sciences from the NIH graduate partnerships program with Johns Hopkins University. She then performed postdoctoral work at the MRC Laboratory of Molecular Biology in Cambridge, UK.

The Shao Lab studies cellular mechanisms that surveil different steps of protein biosynthesis to regulate gene expression and maintain protein homeostasis. How quality control factors distinguish rare aberrant products from similar biosynthetic intermediates is a fundamental problem in biomedical science. The Shao Lab biochemically reconstitutes quality control pathways that act on ribosomes during protein synthesis and that sort membrane proteins to different organelles. Combining these experimental systems with mechanistic and structural approaches generates molecular-level insights into physiological processes essential for cell survival, proliferation, and differentiation.

Steven Gygi

Professor of Cell Biology

Steven Gygi, Ph.D., received his Ph.D. from the University of Utah in Pharmacology and Toxicology performing small molecule mass spectrometry.  He went on to pursue postdoctoral work with Ruedi Aebersold at the University of Washington in 1996.  A revolution in biological mass spectrometry was occurring which allowed for the measurement of protein expression levels and a new field, Proteomics, was born.  In 2000, Dr. Gygi moved to Harvard Medical School and joined the Department of Cell Biology.  Currently, he is the faculty director of two MS core facilities (Taplin Biological MS Facility, and the Thermo Fisher Center for Multiplexed Proteomics—TCMP@HMS).

Research in the Gygi lab centers around developing and applying new technologies in the field of mass spectrometry-based proteomics.  These include the systematic and proteome-wide measurements of many protein properties including their expression levels, modification states, structure, localization, function, and interactions.  For example, the Gygi lab, together with the Harper lab at HMS, is creating a genome-scale map of the protein-protein interaction landscape in cells (termed BioPlex).  In addition, sample multiplexing techniques like Tandem Mass Tags (TMT) are being improved to allow up to 16 proteomics samples to be analyzed simultaneously using high resolution mass spectrometry.

Alfred Goldberg

Professor of Cell Biology

Fred Goldberg, Ph.D., did both undergraduate and graduate work at Harvard, and was appointed to a faculty position in the Department of Physiology, and later, in the Department of Molecular and Cellular Physiology, which were precursors to today's Department of Cell Biology. He has received many honors for his pioneering work, including the discoveries of the uniquitin-protesome pathway and ATP-dependent proteases. His research resulted in the development of proteosome inhibitors, including bortezomib/Velcade, used worldwide as the primary treatment for multiple myeloma.

The Goldberg laboratory is presently studying the regulation and mechanisms of protein breakdown in animal and bacterial cells.

Daniel Finley

Professor of Cell Biology

Dan Finley, Ph.D., received his undergraduate degree from Harvard University in biochemistry, and his graduate degree from MIT, with a focus on molecular biology. He stayed at MIT for his postdoctoral training before joining the Department of Cell Biology at HMS in 1988. He also currently sits on the Scientific Advisory Boards of Proteostasis and X-Chem Pharmaceuticals, and is a consultant for Genentech.

The Finley lab is interested in the ubiquitin-proteasome pathway and related regulatory systems. Specific topics include the mechanism of the proteasome, ubiquitin-like proteins, antizyme, and nonproteolytic functions of ubiquitination.

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