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.
National Emerging Infectious Disease Lab
Genome Science Institute
Probing Pathomechanisms of Enterovirus D68 Infection
03/01/2020 - 02/28/2022 (PI)Charles H. Hood Foundation
Publications listed below are automatically derived from MEDLINE/PubMed and other
sources, which might result in incorrect or missing publications. Faculty can
to make corrections and additions.
Showing 10 of 28 results.
Ejemel M, Li Q, Hou S, Schiller ZA, Tree JA, Wallace A, Amcheslavsky A, Kurt Yilmaz N, Buttigieg KR, Elmore MJ, Godwin K, Coombes N, Toomey JR, Schneider R, Ramchetty AS, Close BJ, Chen DY, Conway HL, Saeed M, Ganesa C, Carroll MW, Cavacini LA, Klempner MS, Schiffer CA, Wang Y. A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction. Nat Commun. 2020 08 21; 11(1):4198. PMID: 32826914
Pfaender S, Mar KB, Michailidis E, Kratzel A, Boys IN, V'kovski P, Fan W, Kelly JN, Hirt D, Ebert N, Stalder H, Kleine-Weber H, Hoffmann M, Hoffmann HH, Saeed M, Dijkman R, Steinmann E, Wight-Carter M, McDougal MB, Hanners NW, Pöhlmann S, Gallagher T, Todt D, Zimmer G, Rice CM, Schoggins JW, Thiel V. LY6E impairs coronavirus fusion and confers immune control of viral disease. Nat Microbiol. 2020 Jul 23. PMID: 32704094
Huang J, Hume AJ, Abo KM, Werder RB, Villacorta-Martin C, Alysandratos KD, Beermann ML, Simone-Roach C, Olejnik J, Suder EL, Bullitt E, Hinds A, Sharma A, Bosmann M, Wang R, Hawkins F, Burks EJ, Saeed M, Wilson AA, Mühlberger E, Kotton DN. SARS-CoV-2 Infection of Pluripotent Stem Cell-derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response. bioRxiv. 2020 Jun 30.View Related Profiles. PMID: 32637964
Ejemel M, Li Q, Hou S, Schiller ZA, Wallace AL, Amcheslavsky A, Yilmaz NK, Toomey JR, Schneider R, Close BJ, Chen DY, Conway HL, Mohsan S, Cavacini LA, Klempner MS, Schiffer CA, Wang Y. IgA MAb blocks SARS-CoV-2 Spike-ACE2 interaction providing mucosal immunity. bioRxiv. 2020 May 15. PMID: 32511396; DOI: 10.1101/2020.05.15.096719;
Esswein SR, Gristick HB, Jurado A, Peace A, Keeffe JR, Lee YE, Voll AV, Saeed M, Nussenzweig MC, Rice CM, Robbiani DF, MacDonald MR, Bjorkman PJ. Structural basis for Zika envelope domain III recognition by a germline version of a recurrent neutralizing antibody. Proc Natl Acad Sci U S A. 2020 05 05; 117(18):9865-9875. PMID: 32321830
Dao Thi VL, Wu X, Belote RL, Andreo U, Takacs CN, Fernandez JP, Vale-Silva LA, Prallet S, Decker CC, Fu RM, Qu B, Uryu K, Molina H, Saeed M, Steinmann E, Urban S, Singaraja RR, Schneider WM, Simon SM, Rice CM. Stem cell-derived polarized hepatocytes. Nat Commun. 2020 04 03; 11(1):1677. PMID: 32245952
Pfaender S, Mar KB, Michailidis E, Kratzel A, Hirt D, V'kovski P, Fan W, Ebert N, Stalder H, Kleine-Weber H, Hoffmann M, Hoffmann HH, Saeed M, Dijkman R, Steinmann E, Wight-Carter M, Hanners NW, Pöhlmann S, Gallagher T, Todt D, Zimmer G, Rice CM, Schoggins JW, Thiel V. LY6E impairs coronavirus fusion and confers immune control of viral disease. bioRxiv. 2020 Mar 07. PMID: 32511345
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 11 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
This graph shows the total number of publications by year, by first, middle/unknown,
or last author.
In addition to these self-described keywords below, a list of MeSH based concepts is available here