Original article from The Brink by Kat J. McAlpine. April 6, 2020 First...
Mohsan Saeed, PhD
Assistant Professor, Biochemistry
PhD (Microbiology) University of Tokyo
My laboratory investigates the role that viral proteins, particularly viral proteases, play in remodeling host cells and creating a favorable environment for virus replication. To this end, we take a two-pronged approach: employ modern systems biology methods to get a global view of the virus-host interface and then use classical molecular biology and biochemistry techniques to gain deeper mechanistic insights.
The major focus of my laboratory is to identify and characterize host proteins that are cleaved by viral proteases. For this, we use a relatively unbiased approach to label and capture protein N-termini generated by proteolytic cleavage in virus-infected cells. This powerful proteomics (“degradomics”) approach not only identifies the cleaved proteins but also the site of cleavage within a protein. Once the proteins are identified and their cleavage is validated by orthogonal methods, we then ascertain the functional significance of these cleavages in the virus life cycle.
Besides studying host proteins that we have identified from the degradomics analysis of clinically important enteroviruses, we continue to extend this analysis to viruses from other families with the goal to get a global view of cellular pathways commonly targeted or co-opted by diverse viruses. These studies are expected to provide novel insights into cell biology, antiviral defenses, and disease mechanisms. Also, viral proteases are one of the prime targets for antiviral development, and therefore deeper insights into their function will help improve viral therapeutics.
- Rusanov T, Kent T, Saeed M, Hoang TM, Thomas C, Rice CM, Pomerantz RT. Identification of a small interface between the methyltransferase and RNA polymerase of NS5 that is essential for Zika virus replication. Sci Rep. 2018 Nov 26; 8(1): 17384
- Keeffe JR, Van Rompay KKA, Olsen PC, Wang Q, Gazumyan A, Azzopardi SA, Schaefer-Babajew D, Lee YE, Stuart JB, Singapuri A, Watanabe J, Usachenko J, Ardeshir A, Saeed M, Agudelo M, Eisenreich T, Bournazos S, Oliveira TY, Rice CM, Coffey LL, MacDonald MR, Bjorkman PJ, Nussenzweig MC, Robbiani DF. A combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates. Cell Reports. 2018 Nov 6; 25(6): 1385-1394