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 R35 million stipend from the National Institute of General Medical Sciences along with a five-year R01 2.5 million bursary bursary of the National Institute of Allergy and Infectious Diseases. It is extremely rare for an early stage researcher to receive these highly competitive awards in the same funding cycle.

Human cells respond to foreign substances such as pathogens and toxins by initiating a powerful innate defense response that creates a protective environment within 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 aimed at avoiding both overactivation and underactivation of the immune system, both of which can lead to tissue damage, organ dysfunction, and microbial disease.

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With his R35 award, Saeed and his colleagues hope to gain new insights into the role of proteases (enzymes that break down proteins and peptides) in regulating cellular defenses and develop strategies to improve the performance of innate defense mechanisms against a Escalation to support 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. Little is currently known about how enteroviruses alter the biology of infected cells. With his R01 grant, Saeed plans to elucidate the role of enteroviral proteases in altering the host cell environment during infection.

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Saeed received his MPhil in Microbiology from Quaid-e-Azam University, Pakistan, where he studied the molecular epidemiology of polio-like viruses in patients with paralysis. He then moved to the University of Tokyo and received his doctorate in pathology, immunology and microbiology. During his PhD, he developed novel cell culture systems to study the hepatitis C virus (HCV) and studied different aspects of this virus in different in vitro and in vivo settings.

He then joined the laboratory of Nobel laureate Dr. Charles M. Rice at Rockefeller University in New York. Although his research at Rice Lab focused primarily on HCV, he also gained experience 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 unbiased identification of cellular proteins cleaved during viral infections.

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Saeed joined BUSM in 2019; his group studies 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 turned to SARS-CoV-2 research and has since made contributions to the molecular understanding of how SARS-CoV-2 establishes infection in different tissues and with the innate human interacts and adaptive immune system.


Boston University School of Medicine

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