BU investigator wins highly competitive awards to study the role of proteases in regulation of cellular defenses

Mohsan Saeed, PhD, assistant professor of biochemistry at Boston University School of Medicine (BUSM), has received a five-year, $2 million R35 grant from the National Institute of General Medical Sciences, as well as a five-year, $2.5 million R01 grant from the National Institute of Allergy and Infectious Diseases. It is extremely rare for an early-stage investigator to win these highly competitive awards during the same funding cycle.

Human cells respond to foreign agents such as pathogens and toxins by initiating a strong innate defense response that creates a protective environment in the cells and incapacitates the invading pathogens and foreign substances. The initiation, activation and resolution of this innate defense response is a carefully regulated process designed to avoid both hyperactivation and underactivation of the immune system, either of which can lead to tissue damage, organ dysfunction and microbial diseases.

With his R35 award, Saeed and his colleagues hope to generate new knowledge about the role of proteases (enzyme which breaks down proteins and peptides) in the regulation of cellular defenses and inform the development of strategies to improve the performance of innate defense mechanisms against escalating microbial and environmental threats.

Enteroviruses are human pathogens that replicate in multiple organs and cause a variety of diseases, including gastroenteritis, pneumonia, myocarditis and encephalitis. Currently, little is known about how enteroviruses alter the biology of infected cells. Using his R01 grant, Saeed plans to clarify the role of enteroviral proteases in changing the host cell environment during infection.

Saeed received his MPhil in microbiology from Quaid-e-Azam University, Pakistan, where he studied the molecular epidemiology of polio-like viruses in patients suffering from paralysis. He then joined the University of Tokyo, receiving his PhD in pathology, immunology and microbiology. During his doctoral studies, he developed novel cell culture systems for the study of hepatitis C virus (HCV) and investigated various aspects of this virus in diverse in vitro and in vivo settings.

He then entered the laboratory of Nobel Laureate Dr. Charles M. Rice at the Rockefeller University, New York, for his postdoctoral training. Although his research in the Rice Lab mainly focused on HCV, he also gained expertise with a number of other positive-strand RNA viruses, including enteroviruses, flaviviruses and alphaviruses. In addition, Saeed developed a novel "viral degradomics" technique that allows an unbiased identification of cellular proteins cleaved during viral infections.

Saeed joined BUSM in 2019; his group explores the role of viral and host proteases in disease mechanisms of positive-strand RNA viruses at the National Emerging Infectious Diseases Laboratories (NEIDL). In early 2021 when COVID-19 was declared a global pandemic, his lab pivoted to SARS-CoV-2 research and has since made contributions to the molecular understanding of how SARS-CoV-2 establishes infection in various tissues and interacts with the human innate and adaptive immune systems.