Membrane Biology

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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.

Adrian Salic

Adrian Salic
Professor of Cell Biology

Adrian Salic, Ph.D. was appointed Assistant Professor of Cell Biology in 2005, after completing his postdoctoral research in the Department of Systems Biology at Harvard Medical School. He received his PhD from Harvard University in 2000. His development of novel tools to detect DNA and RNA synthesis resulted in the creation of the commerically-available "Click-iT" EdU and EU kits that are now widely used by labs around the world.

The Salic lab studies biochemical and cellular mechanisms involved in signal transduction through the Hedgehog signaling pathway. We also develop and apply new chemical technologies to study the cell biology of lipids.

Tom Rapoport

Professor of Cell Biology
HHMI Investigator

Tom Rapoport, Ph.D., joined the faculty at Harvard Medical School in 1995. He received his Ph.D. in Biochemistry from the Humboldt University in East-Berlin for work in enzymology. He then focused on mathematical modeling of metabolism, for which he received his second degree (Habilitation) from the same institution. Before moving to the US, he worked at the Central Institute of Molecular Biology of the Academy of Sciences of the GDR and later at the Max-Delbrueck Center for Molecular Medicine in Berlin-Buch. In 1997, he became a Howard Hughes Medical Institute Investigator.

The Rapoport Lab is interested in the mechanisms by which proteins are transported across membranes, how misfolded proteins are degraded, and how organelles form and maintain their characteristic shapes. Most of the projects center around the endoplasmic reticulum (ER). One project concerns the molecular mechanism by which proteins are translocated across the ER membrane or across the plasma membrane in bacteria and archaea. Much of the current work deals with ERAD (ER-associated protein degradation), a process in which misfolded proteins are retro-translocated across the ER membrane into the cytosol. Major questions concern the mechanism by which proteins move across the membrane and are extracted by the Cdc48 ATPase. Another project concerns the mechanism by which ER morphology, specifically the tubular ER network, is generated. More recently, the Rapoport lab has started to study how proteins are imported into peroxisomes, and how lung surfactant proteins generate lamellar bodies. The lab employs a variety of different techniques, including biochemical methods, such as reconstitutions with purified proteins, and structural biology methods, including X-ray crystallography and cryo-electron microscopy.

Robert V. Farese, Jr.

Bob Farese
Chair & Professor of Molecular Metabolism (Harvard T.H. Chan SPH)
Professor of Cell Biology

Robert Farese, Jr., M.D., is Chair and Professor of the Department of Genetics and Complex Diseases at the Harvard Chan School of Public Health, and Professor of Cell Biology at Harvard Medical School, where he runs a laboratory jointly since 2014 with Dr. Tobias Walther. Dr. Farese obtained his M.D. from Vanderbilt University, did medical training at the University of Colorado, and his postdoctoral research training at UCSF and the Gladstone Institutes. Dr. Farese was an investigator at Gladstone/UCSF from 1994-2014, where his laboratory focused on lipid and energy metabolism, in particular elucidating the biochemical and cell biological pathways of neutral lipid and triglyceride synthesis and storage. Since 2007, Dr. Farese also works in the field of neurodegenerative diseases, with an emphasis on investigating lipid metabolism in the central nervous system. He serves on the board of the Bluefield Project to Cure FTD.

The Farese & Walther Lab investigates cellular lipid and energy metabolism, in particular the mechanisms and physiology of neutral lipid synthesis and storage in lipid droplets. More broadly the lab studies the mechanisms how cells regulate the abundance of lipids, how they store lipids to buffer fluctuation in their availability, and how these processes function in membrane biology and cell physiology.

Tobias Walther

Tobias Walther, Ph.D.
Professor of Molecular Metabolism (Harvard T.H. Chan SPH)
Professor of Cell Biology
HHMI Investigator

Tobi Walther, Ph.D., received his PhD in biology from the European Molecular Biology Laboratory and Ludwig-Maximilians University in Munich, and trained as a postdoc in the Department of Biochemistry and Biophysics at UCSF. He became a Group Leader at the Max Planck Institute of Biochemistry in Martinsried, Germany. In 2010, he relocated his lab and became Associate Professor of Cell Biology at the Yale School of Medicine. In 2014, Dr. Walther joined the Harvard Chan School of Public Health’s Department of Genetics and Complex Diseases, and studies the mechanisms of lipid and membrane homeostasis in cells and organisms with his scientific partner, Bob Farese Jr.

The Farese & Walther laboratory determines the mechanisms how cells regulate the abundance of lipids, how they store lipids to buffer fluctuation in their availability and how these processes function in membrane biology and cell physiology.

Maofu Liao

Maofu Liao
Associate Professor of Cell Biology

Maofu Liao, Ph.D., is an Associate Professor of Cell Biology at Harvard Medical School. He received his Ph.D. from Albert Einstein College of Medicine in 2006, performed postdoctoral research at University of California, San Francisco, and joined the faculty in the Department of Cell Biology of Harvard Medical School in 2014. 

Research in the Liao Lab focuses on understanding the structure and function of membrane proteins and DNA/RNA-protein complexes. The major techniques include single-particle cryo-electron microscopy (cryo-EM) and a variety of biochemical assays. The Liao lab is particularly interested to reveal the mechanism of how proteins sense, move and convert specific lipid molecules. This is achieved by obtaining high-resolution structures of lipid-interacting proteins, and by studying the conformational dynamics of membrane proteins in lipid bilayer environment.

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.

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