A Boston University researcher wins highly competitive awards for studying the role of proteases in regulating cellular defenses

Mohsen Saeed, Ph.D., Assistant Professor of Biochemistry at Boston University School of Medicine (BUSM), was awarded a five-year grant of $2 million R35 from the National Institute of General Medical Sciences, as well as a five-year grant of $2.5 million R01 grant from the National Institute For allergies and infectious diseases. It is extremely rare for an early stage investigator to win such 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 inactivates invading pathogens and foreign matter. The initiation, activation, and resolution of this innate defensive response is a carefully regulated process designed to avoid both overactivity and underactivity of the immune system, both of which can lead to tissue damage, organ dysfunction, and bacterial disease.

With the R35 award, Said and colleagues hope to build new knowledge about the role of proteases (the enzyme that breaks down proteins and peptides) in regulating cellular defenses and inform the development of strategies to improve the performance of innate defense mechanisms against escalation. 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 Grant R01, Said plans to elucidate the role of intestinal proteases in altering the host cell environment during infection.

Saeed holds a Master’s degree in Microbiology in Microbiology from Quaid-e-Azam University, Pakistan, where he studied the molecular epidemiology of polio-like viruses in paralyzed patients. He then attended the University of Tokyo and earned a Ph.D. in pathology, immunology, and microbiology. During his PhD, he developed new cell culture systems to study hepatitis C virus (HCV) and investigated different aspects of this virus in various laboratory and in vivo environments.

Then he entered the laboratory of Dr. Charles M. Rice is a Nobel Laureate at The Rockefeller University, New York, to receive postdoctoral training. Although his research at Rice’s lab focused primarily on HCV, he also gained experience with a number of other positive RNA viruses, including enteroviruses, flaviviruses, and alphaviruses. In addition, Said has developed a new ‘viral lysis’ technique that allows unbiased identification of cleaved cellular proteins during viral infection.

Saeed joined BUSM in 2019; His group is exploring the role of viral and host proteases in strand positive RNA virus disease mechanisms at Emerging National Infectious Disease Laboratories (NEIDL). In early 2021 when COVID-19 was declared a global pandemic, his lab turned to SARS-CoV-2 research and has since made contributions to the molecular understanding of how SARS-CoV-2 creates infections in different tissues and interacts with the human innate and adaptive immune system.