Specialty Division

Cancer and Immunobiology

Research Expertise

Regulation of cytoskeletal dynamics in T cells and dendritic cells, and cytoskeletal control of the immune response

Keywords: T cells, dendritic cells, signaling, cell migration, antigen presentation, cytoskeletal dynamics, protein traffic, immunodeficiency, autoimmunity, vaccine development, cancer immunotherapy, integrins

Research Summary
The focus of my lab is on the role of the cytoskeleton in T cell and dendritic cell function. The cytoskeleton is intimately involved in determining the efficiency and the fidelity of the immune response. For example, when a cytotoxic T cell recognizes a tumor cell for lysis, specific receptor interactions trigger capping of the cortical actin cytoskeleton, creating a specialized membrane domain that is important for T cell signaling events leading to lysis of the tumor cell. Similar processes are important for directing and modulating T cell help. In dendritic cells, actin regulatory proteins control the uptake and presentation of antigens, migration of antigen-bearing cells from sites of infection to lymphoid organs, and defining the outcome of T cell stimulation. Our long-term goals in the lab are to understand how receptor-ligand interactions at the cell surface trigger remodeling of the cytoskeleton, and how the cytoskeleton in turn affects the immune response. Proteins of current interest in the lab include WASP, an actin regulatory protein involved in immunodeficiency disease, HS1, a related protein implicated in autoimmune disease, and Crk family adapter proteins, proteins that control T cell adhesion and migration.

Rotation Projects:
Possible rotation projects are always changing. Topics could include analyzing regulation of T cell actin dynamics at the immunological synapse, analyzing actin function during antigen presentation in dendritic cells, or manipulating cytoskeletal signaling pathways to modify T cell migration during T cell immunotherapy.

Lab Personnel:
Nathan Roy, Postdoctoral Fellow
Shuixing Li, Research Associate
Edward Williamson, Research Associate
Vidhi Chandra, Research Technician

Itmat Expertise

Research in the lab centers on the role of the cytoskeleton in T cell and dendritic cell function. In particular, we are studying the role of actin binding proteins such as ezrin, moesin, fascin and alpha-actinin in modulating cell signaling and cell migration via changes in cell stiffness and ligand mobility.

Graduate Groups

Cell and Molecular Biology
Immunology

Education

AB (Biology), Washington University, 1983
PhD (Microbiology and Immunology), Duke University, 1989

Specialty Certification

Postgraduate Training

Predoctoral Fellow, Cell and Molecular Biology Program, Department of Microbiology and Immunology, Duke University, 1983-88
Postdoctoral Fellow, Department of Microbiology and Immunology, Duke University, 1989-93
Postdoctoral Fellow, Cell Biology Programme, European Molecular Biology Laboratory (EMBL), Germany, 1993-96

Awards and Honors

Phi Beta Kappa National Honor Society, 1982
NIH Pre-doctoral Fellowship, 1983-88
Biology Honors, Washington University, 1983
Sigma Xi National Scientific Honor Society, 1986
R. Burns Prize to Outstanding Graduate Student of the Year, Dept of Microbiology and Immunology, Duke University, 1988
Recipient, Bane Trust Fund, 1996
Young Investigator Award, Cancer Research Foundation, 1997
Recipient, Louis Block Fund, 1997
Career Development Award, Schweppe Foundation, 1998
Evelyn and George Willing Endowed Chair in Pathology Research, Children's Hospital of Philadelphia, 2008-23
Distinguished Mentor Award, Penn Biomedical Postdoctoral Programs, 2017
Simon Flexner Award for Contribution to Graduate Education, Department of Pathology and Laboratory Medicine, Penn Medicine, 2018

Memberships and Professional Organizations

American Society for Cell Biology, 1986-present
Human Frontier Science Program (France), External Reviewer, 2000-present
Wellcome Trust (England), External Reviewer, 2000-present
Telethon Italia (Italy), External Reviewer, 2000-present
German Research Foundation, External Reviewer, 2000-present
Israeli Science Foundation, External Reviewer, 2000-present
Medical Research Council (England), External Reviewer, 2000-present
Institut Pasteur (France), External Reviewer, 2000-present
Chicago Cytoskeleton, Steering Committee, 2001-03
NIH Cell and Molecular Immunology-A Study Section (formerly ALY), 2001-06
NIH ZRG1 CDB-B (02) M Sep Study Section, 2002-23
Abramson Cancer Center, Penn Medicine, 2003-present
-------- Immunology Microscopy Interest Group (PennIMIG), 2008-10
CHOP Research Institute, Children’s Hospital of Philadelphia, 2003-present
-------- Cell Biology Research Affinity Group, 2003-present (Co-Leader, 2019-21)
-------- Vaccines and Immune Therapy Research Affinity Group, 2003-14
-------- Normal and Malignant Hematopoiesis Research Affinity Group, 2020-present
Cell and Molecular Biology Graduate Group (CAMB), University of Pennsylvania, 2003-present
-------- CAMB Admissions Committee, 2004-08
-------- Cell Biology, Physiology, and Metabolism (CPM) Program (Executive Committee, 2007-17, Vice Chair, 2012-16)
Immunology Graduate Group (IGG), University of Pennsylvania, 2003-present
-------- IGG Student Affairs Committee, 2003-16
-------- IGG Admissions Committee, 2004-16
-------- IGG Executive Committee, 2005-present
-------- IGG Colloquium Committee, 2008-10
-------- IGG Career Development Committee, Chair, 2013-16
Perelman School of Medicine at the University of Pennsylvania, MSTP Admissions Committee, 2003-present
Pennsylvania Muscle Institute, Perelman School of Medicine at the University of Pennsylvania, 2004-present
American Association of Immunologists, 2005-present
-------- Committee on the Status of Women, 2009-11
-------- CSOW Career Advisory Board, 2015-present
Lupus Research Institute, Grant Review Panel, 2008-11
Nano/Bio Interface Center, Perelman School of Medicine at the University of Pennsylvania, 2009-present
Arthritis Foundation, Grant Review Panel, 2009-12
Penn School of Veterinary Medicine, Microscopy Core Advisory Committee, 2010-present
Institute for Translational Medicine and Therapeutics (ITMAT), Perelman School of Medicine at the University of Pennsylvania, 2011-present
Institute for Immunology and Immune Health (I3H; fka Institute for Immunology), Penn Medicine, 2013-present
Protective Immunity and Immunopathology Research Affinity Group, Children’s Hospital of Philadelphia, 2014-present
Penn Orphan Disease Center, Perelman School of Medicine at the University of Pennsylvania, 2015-present
European Molecular Biology Alumni Association, Germany, 2015-present
CHOP Diversity Fellowship Advisory Committee, 2016-present (Chair, 2016-20)
CHOP Research Trainee Advisory Committee, 2016-present (Chair, 2017-20)
Penn-PREP Advisory Board, 2016-present
NIH Cancer Immunology and Immunotherapy Fellowship Panel (ZRG FO9CY(20)), 2017
CHOP Building a Diverse Workforce Working Group, 2022-23
CHOP HR Clinical Research and Technical Career Ladder Working Group, 2023-present

Web Links

Selected Publications

Search PubMed for articles