Professor, Department of Biochemistry & Molecular Biology
Dr. Singh’s laboratory studies molecular and cellular mechanisms of the generation of antibody responses against pathogens and vaccines. Following the infection, antigen (expressed by pathogens) specific B cells develop into plasma cells. Plasma cells are factories for producing antibodies molecule that neutralize the invading pathogens. A single plasma cell produces approximately ten thousand antibody molecule per second. Dr. Singh’s laboratory found that Ufbp1/DDRGK1, an essential component of the ufmylation pathway plays an essential role in the development of plasma cells. Plasma cells possess a dense network endoplasmic reticulum, an organelle (chamber), where antibody molecules are synthesized and folded before their secretion. Dr. Singh also showed that Ufbp1 is required for development of endoplasmic reticulum network in plasma cells. Currently, he is exploring the mechanisms how Ufbp1 and other components of ufmylation pathway regulate development and function of plasma cells.
Survival of plasma cells is directly linked to the longevity of protection a vaccine offers. Have you ever wondered why do we take some vaccines such as MMR only once in our life time, whereas we take DTAP vaccine every 5-10 years? Recently, we are advised to take COVID vaccine/boosters every 6-12 months or so. The reason is the longevity of plasma cell induced by these vaccines. Plasma cells induced by MMR vaccine survive for our lifetime, whereas those induced by DTAP survive for 5-10 years. One of the reasons for frequent COVID vaccine boosters is the emergence of new strains. The second reason is that plasma cells induced by COVID vaccine start dying in approximately 6-7 months or so. Once the plasma cells die, the antibodies produced by them also disappear, which necessitates the requirement of booster shots. Dr. Singh is also studying the factors and mechanisms that regulate the survival of plasma cells.
It is well known that vaccines do not induce a potent immune response in the elderly population. He is also interested in identifying the mechanisms and factors that can boost the vaccine-induced immune responses in aged population.
His other research interests include how T cells are activated and generate immune responses and help other immune cells to successfully eliminate invading pathogens and cancers. Previously he discovered the mechanism underlying dietary fiber-mediated suppression of intestinal inflammation and cancers.
His research is funded by extramural sources such as NIH/NIAID.