BU researcher wins highly competitive prizes to study the role of proteases in the regulation of cellular defense

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 researcher to win these highly competitive awards during the same funding cycle.

Human cells respond to foreign substances such as pathogens and toxins by triggering a strong innate immune response that creates a protective environment in the cells and disables the invading pathogens and foreign substances. Initiating, activating and resolving this innate immune response is a carefully regulated process designed to prevent both hyperactivation and underactivation of the immune system, both of which can lead to tissue damage, organ dysfunction and microbial diseases.

With his R35 prize, Saeed and his colleagues hope to generate new knowledge on the role of proteases (enzyme that degrade proteins and peptides) in the regulation of cellular defenses and the development of strategies to improve the performance of innate defense mechanisms against escalating microbial and environmental threats.

Enteroviruses are human pathogens that multiply 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. With his R01 grant, Saeed aims to clarify the role of enteroviral proteases in altering 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 went to the University of Tokyo, where he obtained his doctorate in pathology, immunology and microbiology. During his doctoral studies, he developed new cell culture systems for the study of the hepatitis C virus (HCV) and investigated different aspects of this virus in various in vitro and in vivo settings.

He then went to the laboratory of Nobel laureate Dr. Charles M. Rice at Rockefeller University, New York, for his postgraduate training. Although his research in the Rice Lab focused primarily on HCV, he also gained expertise in a number of other positive-strand RNA viruses, including enteroviruses, flaviviruses and alphaviruses. In addition, Saeed developed a new “viral degradomics” technique that allows unbiased identification of cellular proteins that are cleaved during viral infections.

Saeed joined BUSM in 2019; his group is investigating 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 focused on SARS-CoV-2 research and has since contributed to the molecular understanding of how SARS-CoV-2 mediates infections in various tissues and interacts with the human innate and adaptive immune system.

Source:

Boston University School of Medicine

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