Cell Cycle, Division, and Proliferation

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Tomas Kirchhausen

Tomas Kirchhausen
Springer Family Chair (BCH)
Senior Investigator, Program in Cellular and Molecular Medicine (BCH)
Professor of Cell Biology
Professor of Pediatrics

The Kirchhausen Lab focuses on understanding processes that mediate and regulate cellular membrane remodeling, the biogenesis of organelles, and the ways by which viruses, biologicals and oligonucleotides are delivered to the cell interior. 

By direct observation of molecular events obtained using Lattice Light Sheet Microscopy and Lattice Light Sheet Microscopy optimized with Adaptive Optics (AO-LLSM), frontier optical-imaging modalities with high temporal resolution and spatial precision, we aim to bridge the gap between molecules and cells, either as independent entities in culture, as components of organoids, or as constituents of living tissues. The richness and magnitude of the big-data obtained over periods ranging from seconds to hours create new challenges for obtaining quantitative representations of the observed dynamics and for deriving accurate and comprehensive models for the underlying developmental mechanisms. With these type of dynamic studies we expect to integrate molecular snapshots obtained at molecular and atomic resolution using cryoEM with live-cell processes, in an effort to generate ‘molecular movies' allowing us to obtain frameworks for analyzing some of the molecular contacts and switches that participate in the regulation, availability, and intracellular traffic of the many molecules involved in signal transduction, immune responsiveness, lipid homeostasis, cell-cell recognition and organelle biogenesis. Such biological phenomena have importance for our understanding of many diseases including cancer, viral infection and pathogen invasion, Alzheimer's, as well as other neurological diseases.

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.

Yang Shi

Group Leader in Cancer Genomics at Ludwig Cancer Research Center.
Investigator
Department of Neonatology (BCH; interim during transition)

Yang Shi, Ph.D., obtained his doctorate from NYU in molecular biology and trained as a postdoctoral fellow at Princeton University. He joined Harvard Medical School as an assistant professor in 1991. He was the Merton Bernfield Professor of Neonatology in the Division of Newborn Medicine at Boston Children's Hospital from 2009-2018, after which he was named the C.H. Waddington Professor of Pediatrics. In 2020, he was appointed a Member of the Oxford Branch of the Ludwig Institute for Cancer Research at the University of Oxford. Yang is a fellow of the American Association for the Advancement of Science and a member of the American Academy of Arts and Sciences.

A major focus of the Shi lab is to understand epigenetic regulation and its role in human diseases. The Shi lab discovered the first histone methyl eraser, LSD1, and they continue to investigate how histone methylation is dynamically regulated as well as mechanisms involved in the recognition of combinatorial modifications occurring on histone tails that are important for chromatin regulation. More recently, the Shi lab has  been studying RNA modifications and how they impact gene expression regulation. At Ludwig Oxford, Yang's lab will be focusing on acute myeloid leukaemia and diffuse intrinsic pontine glioma, two cancers in which chromatin and epigenetics play critical roles.

David Pellman

Margaret M. Dyson Professor of Pediatric Oncology (DFCI)
Professor of Cell Biology
HHMI Investigator

David Pellman, M.D. is the Margaret M. Dyson Professor of Pediatric Oncology at the Dana-Farber Cancer Institute, a Professor of Cell Biology at Harvard Medical School, an Investigator of the Howard Hughes Medical Institute, and the Associate Director for Basic Science at the Dana-Farber/Harvard Cancer Center.  He received his undergraduate and medical degrees from the University of Chicago.  During medical school, he did research at the Rockefeller University.  His postdoctoral fellowship was at the Whitehead Institute/Massachusetts Institute of Technology.

The Pellman Lab works on the mechanism of cell division and how certain cell division errors drive rapid genome evolution.  The normal processes studied in the laboratory have included spindle positioning and asymmetric cell division, the mechanism of spindle assembly and cytokinesis, and the mechanism of nuclear envelope assembly and how it is coordinated with chromosome segregation.  The mutational processes studied in David’s group are particularly important for cancer, but have relevance for genome evolution in other contexts.  Current projects include: the mechanism of a newly discovered mutational process called “chromothripsis”, how the architecture and integrity of the nuclear envelope impacts genome maintenance, and the role of cytoplasmic chromatin in triggering innate immune proinflammatory signaling. The lab uses a variety of approaches which include, molecular genetics, biochemistry, and imaging.  Currently there is a heavy emphasis on using a combination of live-cell imaging and single-cell genome sequencing developed in the lab (“Look-Seq”) to relate the consequences of cell division errors to genome alterations. 

Marcia Haigis

Professor of Cell Biology

Marcia C. Haigis, Ph.D. obtained her Ph.D. in Biochemistry from the University of Wisconsin in 2002 and performed postdoctoral studies at MIT studying mitochondrial metabolism. In 2006, Dr. Haigis joined the faculty of Harvard Medical School, where she is currently a Professor in the Department of Cell Biology. Dr. Haigis is an active member of the Paul F. Glenn Center for the Biology of Aging, a member of the Ludwig Center at Harvard Medical School, and was recently selected for the National Academy of Medicine Emerging Leaders in Health and Medicine Program.

The Haigis Lab aims to: 1) identify molecular mechanisms by which mitochondria respond to cellular stress and 2) elucidate how these cellular mechanisms contribute to aging and age-related diseases, such as cancer. The Haigis lab has made key contributions to our understanding of metabolic reprogramming in cancer, including identifying nodes of metabolic vulnerability in the control of fat oxidation in leukemia and metabolic recycling of ammonia to generate amino acids important for tumor growth.

Joan Brugge

Joan Brugge
Louise Foote Pfeiffer Professor of Cell Biology
Co-Director of the Ludwig Center at Harvard

Joan Brugge, Ph.D., received her Ph.D. in virology from Baylor College of Medicine, and was a postdoctoral researcher at the University of Colorado Medical Center. After professorships at SUNY, Stony Brook and the University of Pennsylvania, where she was an HHMI investigator, she became the Scientific Director and Senior VP at ARIAD Pharmaceuticals. She returned to academia as Professor of Cell Biology at HMS in 1997, and was Chair of the department from 2004-2014. She became Co-Director of the Ludwig Center at Harvard in 2014. She currently sits on the Scientific Advisory Board of the Allen Institute of Cell Sciences.

The Brugge laboratory is investigating the cellular processes and pathways that are involved in normal morphogenesis of epithelial tissues as well as those involved in the initiation and progression of epithelial tumors.

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