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.
Da-Yuan Chen – Postdoctoral Associate
Nazimuddin Khan – Postdoctoral Associate
Alexander Tavares – Graduate Student
Brianna Close – Graduate Student
Hasahn Conway – Research Technician
Research positions are available, please contact Dr. Saeed.
Liu D, Tedbury PR, Lan S, Huber AD, Puray-Chavez MN, Ji J, Michailidis E, Saeed M, Ndongwe TP, Bassit LC, Schinazi RF, Ralston R, Rice CM, Sarafianos SG. Visualization of Positive and Negative Sense Viral RNA for Probing the Mechanism of Direct-Acting Antivirals against Hepatitis C Virus. Viruses. 2019 Nov 08; 11(11). PMID: 31717338
Luna JM, Saeed M, Rice CM. Taming a beast: lessons from the domestication of hepatitis C virus. Curr Opin Virol. 2019 04; 35:27-34. PMID: 30875640
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 11 26; 8(1):17384. PMID: 30478404
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 Rep. 2018 11 06; 25(6):1385-1394.e7. PMID: 30403995
Kuchay S, Saeed M, Giorgi C, Li J, Hoffmann HH, Pinton P, Rice CM, Pagano M. NS5A Promotes Constitutive Degradation of IP3R3 to Counteract Apoptosis Induced by Hepatitis C Virus. Cell Rep. 2018 10 23; 25(4):833-840.e3. PMID: 30355490
Robinson CL, Chong ACN, Ashbrook AW, Jeng G, Jin J, Chen H, Tang EI, Martin LA, Kim RS, Kenyon RM, Do E, Luna JM, Saeed M, Zeltser L, Ralph H, Dudley VL, Goldstein M, Rice CM, Cheng CY, Seandel M, Chen S. Male germ cells support long-term propagation of Zika virus. Nat Commun. 2018 05 29; 9(1):2090. PMID: 29844387
Robbiani DF, Bozzacco L, Keeffe JR, Khouri R, Olsen PC, Gazumyan A, Schaefer-Babajew D, Avila-Rios S, Nogueira L, Patel R, Azzopardi SA, Uhl LFK, Saeed M, Sevilla-Reyes EE, Agudelo M, Yao KH, Golijanin J, Gristick HB, Lee YE, Hurley A, Caskey M, Pai J, Oliveira T, Wunder EA, Sacramento G, Nery N, Orge C, Costa F, Reis MG, Thomas NM, Eisenreich T, Weinberger DM, de Almeida ARP, West AP, Rice CM, Bjorkman PJ, Reyes-Teran G, Ko AI, MacDonald MR, Nussenzweig MC. Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico. Cell. 2017 May 04; 169(4):597-609.e11. PMID: 28475892
Harak C, Meyrath M, Romero-Brey I, Schenk C, Gondeau C, Schult P, Esser-Nobis K, Saeed M, Neddermann P, Schnitzler P, Gotthardt D, Perez-Del-Pulgar S, Neumann-Haefelin C, Thimme R, Meuleman P, Florian WR, De Francesco R, Rice CM, Bartenschlager R, Lohmann V. Erratum: Tuning a cellular lipid kinase activity adapts hepatitis C virus to replication in cell culture. Nat Microbiol. 2017 Jan 23; 2:17012. PMID: 28112725
Harak C, Meyrath M, Romero-Brey I, Schenk C, Gondeau C, Schult P, Esser-Nobis K, Saeed M, Neddermann P, Schnitzler P, Gotthardt D, Perez-Del-Pulgar S, Neumann-Haefelin C, Thimme R, Meuleman P, Vondran FW, De Francesco R, Rice CM, Bartenschlager R, Lohmann V. Tuning a cellular lipid kinase activity adapts hepatitis C virus to replication in cell culture. Nat Microbiol. 2016 12 19; 2:16247. PMID: 27991882
Saeed M, Andreo U, Chung HY, Espiritu C, Branch AD, Silva JM, Rice CM. SEC14L2 enables pan-genotype HCV replication in cell culture. Nature. 2015 Aug 27; 524(7566):471-5. PMID: 26266980
Complete list can be found at BU Profiles