BME Faculty Search Seminar – Nova Pishesha

Exploiting Antigen Presentation Pathways for Precision Immune Engineering

Dr. Nova Pishesha,

Junior Fellow, Society of Fellows at Harvard University

Current treatments for autoimmunity rely on general immunosuppression, which exposes patients to opportunistic infections. Hence, immunoregulatory modalities, which educate the immune system to induce antigen-specific tolerance are desirable. My doctoral research revolved around engineered red blood cells (RBCs) to treat preclinical models of autoimmune diseases by hijacking the tolerogenic RBC clearance pathways. As a postdoctoral fellow, I worked on an alpaca-derived single domain antibody fragment (nanobody)-based platform. I have engineered these nanobodies to efficiently target antigen presenting cells and transmit either tolerogenic or vaccinal signal to antigen-specific immune cells. I showed that a single dose of a VHH that recognizes major histocompatibility complex class II/MHCII (VHHMHCII), conjugated to a myelin peptide and an anti-inflammatory corticosteroid, i.e. dexamethasone (VHHMHCII-MOG-DEX), affords lasting protection in a mouse model of multiple sclerosis (MS). A single dose of VHHMHCII-MOG-DEX also reverses paralyses in mice without compromising the capacity of the immune system to fight pathogens. I further developed this technology for treating type 1 diabetes and as a SARS-CoV-2 vaccine. My independent group will aspire to produce novel treatments for autoimmune and infectious diseases.

Talk will be in-person and virtual, see information below.