Cytoskeletal Biology (Cellular Architecture and Mechanics)

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Radhika Subramanian

Assistant Professor of Genetics (HMS)
Assistant Molecular Biologist (MGH)
Affiliate member of Cell Biology (HMS)

Radhika received her Ph.D. in Biochemistry from Brandeis University. She then performed postdoctoral work at the Rockefeller University. She joined the faculty of the Massachusetts General Hospital and Harvard Medical School in October 2014.

The Subramanian Lab is interested in how micron-length scale structures that are critical for cellular signaling emerge from the collective activity of nanometer-sized proteins. We address this question in the context of microtubule organization for (1) cell division and (2) cilium-dependent Hedgehog signal transduction. We primarily use a reconstitution-based approach and ‘reconstruct’ sub-reactions of these cellular pathways in vitro from purified components. We aim to decipher the fundamental rules that govern the spatial-temporal organization of cellular machines and organelles, such as the spindle and the cilium, through this approach. We employ a wide range of experimental techniques, integrating information from cutting-edge single-molecule methods, high-resolution microscopy, structural tools, and biochemical and cellular read-outs. Through these studies, our goal is to understand the cellular mechanisms relevant to developmental disorders and human cancers.

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.

David Van Vactor

Professor of Cell Biology
Director of Biological and Biomedical Sciences Graduate Program
Program Director/PI of Molecular Cellular and Developmental Dynamics T32
Faculty Director of Harvard Curriculum Fellows Program

David Van Vactor, Ph.D. is a Professor of Cell Biology in the Blavatnik Institute at Harvard Medical School (HMS) and a member of the Program in Neuroscience and the DFCI/Harvard Cancer Center. He is the Faculty Director of the HMS Curriculum Fellows program and Director/PI of Harvard’s Molecular, Cellular and Developmental Dynamics (MCD2) T32 PhD training program. He is also a Visiting Professor at the Okinawa Institute of Science and Technology (OIST) Graduate University in Japan.  Dr. Van Vactor received his B.A. in Behavioral Biology at the Johns Hopkins University and his Ph.D. from the Department of Biological Chemistry at the University of California, Los Angeles (UCLA), before post-doctoral research at the University of California, Berkeley.

The Van Vactor Lab is focused on understanding the development, maintenance and plasticity of neuromuscular connectivity in the model organism Drosophila. The coordinated morphogenesis of the synapse, fundamental unit of cell-cell communication in neural networks, requires many layers of regulatory mechanisms.  Genome-wide enhancer/suppressor screens to define the molecular machinery controlling neuromuscular junction development (NMJ) led us to multiple translational regulators, including a number of microRNA (miR) genes. Because the fly NMJ has served so well for genetic analysis of synapse development and function in many labs, we have a sophisticated knowledge of underling pathways and gene networks, thus making this a system particularly well suited to explore upstream regulatory logic. Using conditional genetic tools to manipulate the function of conserved miRs and their target genes, we have identified several novel regulatory pathways.  In addition, through a close and long-term collaboration with the Artavanis-Tsakonas Lab, we have worked to better understand developmental and age-dependent degeneration of the neuromuscular system using a variety of models for human disease in Drosophila.

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. 

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