||The adaptive immune system protects us from infectious diseases and diverse pathologies (e.g., cancer). The pathogen-specific immunological memory that the adaptive immune system exhibits is the basis for vaccination. The adaptive immune system can also go awry, leading to diverse autoimmune diseases (e.g., multiple sclerosis). Our group is focused on understanding how the adaptive immune system is regulated, and on harnessing this understanding to design vaccines against scourges such as HIV. We confront these challenges by bringing together theoretical and computational studies, rooted in statistical mechanics, with a diversity of biological experiments and clinical data.
A major emphasis of our theoretical and computational studies is to make mechanistic predictions and design therapies that can be directly tested, and the metric of success is uncovering basic principles and impact on experimental and clinical immunology.
We have active collaborations with immunologists around the world. Current research interests are primarily focused on signaling in T and B lymphocytes, development of an antigen specific (yet degenerate) lymphocyte repertoire, the human immune response to HIV, and vaccine design.
"Manipulating the Selection Forces during Affinity Maturation to Generate Cross-Reactive HIV Antibodies", with S. Wang et al., Cell, 160, 785 (2015).
"Coreceptor Scanning by the T Cell Receptor Provides a Mechanism for T Cell Tolerance", with O. Stepanek et al., Cell, 159, 333 (2014).
"Translating HIV Sequences into Quantitative Fitness Landscapes Predicts Viral Vulnerabilities for Rational Immunogen Design", with A. Ferguson et al., Immunity, 38, 606-617 (2013).
“Coordinate Linkage of HIV Evolution Reveals Regions of Immunological Vulnerability”, with V. Dahirel et al., Proc. Natl. Acad. Sci, 108, 11530-11535 (2011).
"Effects of Thymic Selection of the T-Cell Repertoire on HLA Class I-Associated Control of HIV Infection", with A. Košmrlj, Nature, 465, 350 (2010).
"Digital Signaling and Hysteresis Characterize Ras Activation in Lymphoid Cells", with J. Das et al, Cell, 136, 337 (2009).
“CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse”, with Q-J Li et al., Nature Immunology (2004).
“The Immunological Synapse Balances T Cell Receptor Signaling and Degradation”, with K.H. Lee, et al., Science, 302, 1218 (2003).