Arthur Weiss, MD, PhD

Ephraim P. Engleman Distinguished Professor
Professor
Department of Medicine
Research Overview: 

The response of lymphocytes to antigen initiates an antigen specific immune response and also represents a unique opportunity to study how complex molecular circuitry within cells andweiss between cells can lead to developmental decisions, cell differentiation and proliferation. We are interested in understanding how receptors involved in antigen recognition can initiate signal transduction events that regulate cell responses in the immune system. We know that receptors involved in antigen recognition functionally interact with tyrosine kinases and phosphatases, enzymes that regulate protein phosphorylation, to induce signaling pathways that regulate cellular responses and gene expression. We are using genetically selective small molecule inhibitors of kinases together with kinase, phosphatase and substrate mutants to study how thresholds for the initiation of immune responses are set and how feedback circuits influence responses. We would like to understand how the tyrosine kinases and phosphatases in these pathways are regulated and how they control cellular responses in development, in normal immune responses and in autoimmune diseases such as lupus and rheumatoid arthritis.

Primary Thematic Area: 
Immunology
Secondary Thematic Area: 
Cancer Biology & Cell Signaling
Research Summary: 
Our lab focuses on the roles of tyrosine kinases and phosphatases in regulating lymphocyte activation, and studies how abnormalities in tyrosine phosphorylation pathways can lead to immunologically-mediated diseases.

Websites

Publications: 

Bruton's Tyrosine Kinase Membrane Dynamics and Signaling.

Biophysical journal

Laura M. Nocka, Jean K. Chung, Aubrianna Decker, Theresa Kadlecek, Arthur Weiss, John Kuriyan, Jay T. Groves

How the T Cell Signaling Network Processes Information to Discriminate between Self and Cognate Ligands.

Biophysical journal

Raman S. Ganti, Wan-Lin Lo, Darren McAffee, Jay T. Groves, Arthur Weiss, Arup K. Chakraborty

CD45 functions as a signaling gatekeeper in T cells.

Science signaling

Courtney AH, Shvets AA, Lu W, Griffante G, Mollenauer M, Horkova V, Lo WL, Yu S, Stepanek O, Chakraborty AK, Weiss A

Slow phosphorylation of a tyrosine residue in LAT optimizes T cell ligand discrimination.

Nature immunology

Lo WL, Shah NH, Rubin SA, Zhang W, Horkova V, Fallahee IR, Stepanek O, Zon LI, Kuriyan J, Weiss A

Reporters of TCR signaling identify arthritogenic T cells in murine and human autoimmune arthritis.

Proceedings of the National Academy of Sciences of the United States of America

Ashouri JF, Hsu LY, Yu S, Rychkov D, Chen Y, Cheng DA, Sirota M, Hansen E, Lattanza L, Zikherman J, Weiss A