Govinda SharmaBC Cancer Agency · Canada's Michael Smith Genome Sciences Centre
Doctor of Philosophy
Co-founder, Immfinity Biotechnologies
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Citations since 2017
9 Research Items
My goal is to develop and apply tools to allow us to understand the broad landscape of antigens that are recognized by T-cell receptors, which are now understood to be extremely precise, yet highly cross-reactive molecular sensors. Doing this will allow us to understand how T cell antigens actuate cellular responses and orchestrate systemic immune responses, and, importantly, how we can leverage this knowledge to rationally design new immunotherapeutic strategies.
September 2012 - December 2018
I got the chance to go on the Antibuddies podcast to talk about our 2019 Nature Communications paper, discuss some of the work I've been doing since, and just generally have a good time talking about T cells. The link to the full stream is below: https://youtu.be/776qAB_9YuU
KRAS codon 12 mutations are among the most common hotspot mutations in human cancer. Using a functional screening platform we set out to identify αβ T-cell receptors (TCRs) as potential targeting reagents for KRAS G12D and/or KRAS G12V neoepitopes presented by the prevalent HLA-A*02:01 allele. Here we describe isolation and characterization of thre...
Cytotoxic CD8⁺ T cells recognize and eliminate infected or malignant cells that present peptide epitopes derived from intracellularly processed antigens on their surface. However, comprehensive profiling of specific major histocompatibility complex (MHC)-bound peptide epitopes that are naturally processed and capable of eliciting a functional T cel...
Though it is understood that T-cells are a critical component of the immune system’s ability to destroy foreign invaders and attack cancerous cells, very little is known regarding the specific epitopes that are recognized by T-cells to carry out these functions. Generally, the epitopes mediating this immunity are short, contiguous peptides derived...
See the full presentation at the following link: https://youtu.be/hnPJELgmN-0
Despite tremendous potential utility in clinical medicine and research, the discovery and characterization of T-cell antigens has lagged behind most other areas of health research in joining the high-throughput '-omics' revolution. Partially responsible for this is the complex nature of the interactions between effector T cells and antigen-presenti...
Though it is understood that T-cells are a critical component of the immune system’s ability to destroy foreign invaders (such as pathogenic bacteria, viruses, fungi, and parasites) as well as identify and attack cancerous cells, very little is known regarding the specific molecular determinants (antigens) that T-cells recognize in order to carry out these functions. There is a severe lack of linked T-cell receptor/antigen pairs - fewer than 700 verified pairs are described in the literature while hundreds of millions of T-cell receptor sequences have been documented and a nearly limitless number of possible T-cell antigens could exist. I have developed a novel method for high-throughput T-cell antigen discovery that matches the sensitivity of conventional, gold-standard approaches but with the added advantage of being able to query more than a million distinct peptide coding sequences (>100x more than is feasible with conventional methods) for their ability to elicit reactivity from a given TCR. My current work is focused on continuing to benchmark the approach in a variety of model T-cell/antigen systems to open the door for the scientific community to generate linked TCR/antigen data at a scale large enough to allow researchers to better understand basic T-cell biology, develop better predictive models of T-cell reactivity, and rationally design T-cell based immunotherapeutics for the treatment of cancer, infectious diseases, transplant rejection, and autoimmune disorders.