The Faculty

Focus

Immunology, t-cell receptor, molecular recognition, signaling, membrane channels

Biography

1993 University of California, San Diego B.S. 06/93

2001 University of California, Berkeley Ph.D.  05/01

2011 Stanford University Postdoc 11/05

2005-2012 Assistant Professor, Department of Biochemistry and Molecular Biology, The University of Chicago

2012-2015  Associate Professor, Department of Biochemistry and Molecular Biology, The University of Chicago

2015-present  Professor, Department of Biochemistry and Molecular Biology, The University of Chicago

2017-present  Joseph Regenstein Professor in Biochemistry and Molecular Biology, The University of Chicago

Honors

  • 2009-11 Kavli Fellow
  • 2007-10 Searle Scholar
  • 2007 Cancer Research Foundation Junior Investigator Award
  • 2004-05 NIH Postdoctoral Training Grant
  • 2001-04 Cancer Research Institute Postdoctoral Fellowship
  • 2002 Henzl-Gabor Travel Fellowship
  • 2001 Katherine McCormick Fund for Women
  • 1999 Department of Integrative Biology Research Grant
  • 1998 Department of Integrative Biology Research Grant
  • 1993 Graduate, Cum Laude
  • 1993 Phi Beta Kappa
  • 1993 Golden Key National Honor Society

Research Interests

Our lab is focused on understanding how events at the molecular level (i.e. protein-protein interactions) allow the immune system to discriminate between self and non-self.  Several of the projects in the lab focus on studying the molecular recognition mechanisms of unconventional T cells including γδ T cells, a lineage of T cells that remain much of an enigma in how they function in the vertebrate immune response.  We approach this problem at many different levels:  genetics, protein biochemistry, structure, biophysics and cell biology/imaging.

What do γδ T cells recognize as ligands and how do they do it? γδ T cells constitute a minority (1-5%) of circulating T cells but are prevalent in epithelial tissues such as the digestive, reproductive and respiratory tracts. These cells perform a variety of effector functions ranging from cytokine release and cytotoxicity to immune modulation and wound healing. With the exception of a few defined ligands, it is essentially unknown what signals activate the effector functions of these cells through their T cell receptors (TCRs). We are studying the features of γδ TCRs that modulate T cell recognition. We are also pursing other ligands for γδ T cells, studying them by combining flow cytometry (FACS), biophysical measurements such as SPR, and structure determination using x-ray crystallography. 

Lipids as antigens in immune recognition. We are interested in how the immune system discriminates between self and non-self through receptor/ligand interactions. Conventional αβ T cells do so through recognition of peptide presented in the context of MHC molecules, but our interest lies in how lipids can be used for self/non-self recognition. Some of our studies  include structural, biophysical and functional studies of T cells that respond to the lipid presenting MHC molecules CD1c and CD1d. 

Presentation of metabolites by the MHC-like molecule MR1: We and others have shown that the MHC-like molecule, MR1 presents small-molecule antigens that derive from the metabolic pathways of B vitamins such as riboflavin and folic acid.  These small molecules all have ring structures (pterin or lumazine) that are compatible with the binding cavity of MR1, which is lined with aromatic residues (tyrosines, tryptophans and phenylalanines). MR1 presents these metabolic antigens to a T cell population called MR1Ts (MR1 restricted T cells).  We are currently investigating other metabolites that can be presented by MR1 in the context of infection that can serve to activate MR1Ts.  We use a variety of techniques to investigate this system:  structural biology, protein engineering, cell assays and are closely collaborating with other groups to define and study these antigens.