Structural Biology

Home / Research Areas / Structural Biology

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.

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.

Danesh Moazed

Professor of Cell Biology
HHMI Investigator

Danesh Moazed, Ph.D., is a Professor and HHMI Investigator in the Department of Cell Biology at Harvard Medical School.  He is a member of the Harvard Biophysics Program and the Harvard Initiative for RNA Medicine (HIRM). He received his undergraduate and Ph.D. degrees from the University of California in Santa Cruz and performed postdoctoral studies at the University of California in San Francisco.

The Moazed lab studies how genes are silenced and how silencing is epigenetically inherited across generations.  The lab’s interests revolve around diverse pathways of heterochromatin-mediated gene silencing in yeast and mammalian cells.  Work in budding yeast focuses on the structure and function of a diverged and relatively simple form of heterochromatin, which requires only three Silent information regulator (“Sir”) proteins that form a histone deacetylase and chromatin-binding complex.  Work in fission yeast focuses on a conserved example of heterochromatin that requires the nuclear RNA interference (RNAi) machinery, other RNA processing pathways, Heterochromatin protein 1 (HP1) homologs, and histone-modifying enzymes.  In mammalian cells, the work is focused on HP1-mediated and other heterochromatin formation pathways.  The lab uses approaches ranging from genetics and genomics, biochemical purification and reconstitution, and structural biology for their studies.  Ultimately, the lab seeks to understand the conserved fundamental principles that govern the assembly, function, and epigenetic propagation of heterochromatin.

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.

Chris Sander

Professor in Residence of Cell Biology
Director of cBio Center (DFCI)

Chris Sander, Ph.D., received a Master's Degree in physics from Berkeley, followed by a Ph.D. at SUNY, Stony Brook in theoretical physics. He did a postdoc in molecular biology at the Weizmann Institute. He was the founding Director and Department Chair of the Computational Biology Center and Program at Memorial Sloan Kettering Cancer Center from 2002-2015, after which he joined HMS as a Professor-in-Residence of Cell Biology. He is the Director of cBio Center at the Dana-Farber Cancer Institute.

The overall goal of the Sander lab is to solve biological problems using quantitative methods from bioinformatics, statistical physics, data sciences, statistics, computer science, and mathematics. We apply these computational methods to build predictive network models of molecular and cell-cell interactions, to support cancer precision medicine, and to make discoveries in structural and evolutionary biology.

Subscribe to RSS - Structural Biology