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A.Sc. University of Houston, 2008;
B.Sc. University of Kansas, 2010;
Ph.D. University of Kansas, 2016;
Postdoctoral Research, University of California Santa Cruz, 2016-2020
Postdoctoral Research, University of Pennsylvania & Children’s Hospital of Philadelphia, 2020-2022
The questions that keep us up at night are: How does the immune system present and recognize antigens to combat disease? What are the molecular features involved in stimulating robust and specific immune responses? How can we exploit distinct features of immune recognition to develop new treatments for disease? Our research centers on answering these important questions.
We focus on the CD1 family of major histocompatibility complex class I (MHC-I) related proteins, which present both self and foreign lipids to αβ, γδ, and natural killer T cells. Examples of CD1 complexes involved in the adaptive and innate immune response to human disease include those associated with lipids derived from cancerous cells (Leukemia, Carcinoma, Lymphoma, Melanoma), wasp/bee venom including yellowjackets of the genus Vespula who represent Georgia Tech's mascot Buzz (Hymenoptera venom allergy), bacterial pathogens (Mycobacterium tuberculosis - Tuberculosis, Borrelia burgdorferi - Lyme Disease, Pseudomonas aeruginosa - Pneumonia), viral pathogens (HSV-1 - Herpes, HBV - Hepatitis B), marine sponges, and self cells in autoimmune disease (Dermatitis, Psoriasis, Lysosomal Storage Disease). Recent studies have shown that CD1 can also associate with and present a much broader range of antigens, such as skin oils that lack a discernible hydrophilic head group, lipopeptides, and non-lipid small molecules. Unlike peptide antigen presentation by high polymorphic human MHC-I complexes for which therapeutics must be tailored to a patients genetic background, the non-polymorphic nature of CD1 means that lipid/CD1 molecules are attractive candidates for donor-unrestricted (i.e. universal and patient-haplotype independent) vaccines and immunotherapy treatments. Progress in the development of lipid/CD1 mediated therapies has been hindered by an incomplete understanding in several important features of the CD1 antigen processing and presentation pathway as well as a lack of structural information for clinically relevant lipid/CD1 complexes. We aim to address these knowledge gaps with our research.
Our goals are to i. understand how lipid antigens are selected and loaded onto CD1 molecules in various cellular compartments, ii. solve macromolecular structures of CD1 complexes with different disease-associated lipids antigens, iii. characterize how T cell receptors engage lipid/CD1 molecules towards activation of the immune response, iv. design lipid-based sensors of disease, and v. engineer T cell receptors (TCRs) and chimeric antigen receptors (CARs) with enhanced affinity and specificity for lipid/CD1 complexes to eliminate diseased cells. With structure, function, and design principles in hand, we become uniquely situated to develop novel immunotherapies targeting lipids associated with tumor cells, pathogen infected cells, or autoreactive cells.
The McShan lab is not focused on any particular approach or technique, although we are particularly fond of solution nuclear magnetic resonance (NMR) spectroscopy. We strive to solve outstanding biological questions with relevance to immunology, medicine, and pathology. Trainees joining our lab will gain hands on experience in biochemical/biophysical characterization of protein-protein and lipid-protein interactions (surface plasmon resonance, isothermal titration calorimetry, hydrogen/deuterium exchange mass spectroscopy), structural biology (solution NMR, X-ray crystallography, cryo-electron microscopy), computational biology (Rosetta modeling, molecular dynamics simulations), protein design/engineering, chemical biology, and immunological assays.
We openly welcome members of the LGBTQAI+ community, women, disabled scientists (including those with invisible disabilities), and scientists of color.