Arthur Weiss, MD, PhD

Ephraim P. Engleman Distinguished 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: 
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.



TCR signaling promotes formation of an STS1-Cbl-b complex with pH-sensitive phosphatase activity that suppresses T cell function in acidic environments.


Tsai YL, Arias-Badia M, Kadlecek TA, Lwin YM, Srinath A, Shah NH, Wang ZE, Barber D, Kuriyan J, Fong L, Weiss A

Stimulation of ectopically expressed muscarinic receptors induces IFN-γ but suppresses IL-2 production by inhibiting activation of pAKT pathways in primary T cells.

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

Nguyen TTT, Lu W, Zhu WS, Ansel KM, Liang HE, Weiss A

Overcoming inhibitory constraints to TCR signaling by targeting the pH-sensitive phosphatase suppressor of T-cell receptor signaling 1 (STS1).

The Journal of Immunology

Yuan-Li Tsai, Marcel Arias Badia, Theresa A Kadlecek, Neel H Shah, Lawrence Fong, Arthur Weiss