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.
- Faculty, National Emerging Infectious Disease Lab, Boston University
- Member, Genome Science Institute, Boston University
- Published on 8/10/2023
Lin L, Chen DY, Scartelli C, Xie H, Merrill-Skoloff G, Yang M, Sun L, Saeed M, Flaumenhaft R. Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication. iScience. 2023 Sep 15; 26(9):107602. PMID: 37664626.
- Published on 7/26/2023
Datta S, Chen DY, Tavares AH, Reyes-Robles T, Ryu KA, Khan N, Bechtel TJ, Bertoch JM, White CH, Hazuda DJ, Vora KA, Hett EC, Fadeyi OO, Oslund RC, Emili A, Saeed M. High-resolution photocatalytic mapping of SARS-CoV-2 spike interactions on the cell surface. Cell Chem Biol. 2023 Jul 26. PMID: 37499664.
- Published on 7/21/2023
Feng S, O'Brien A, Chen DY, Saeed M, Baker SC. SARS-CoV-2 nonstructural protein 6 from Alpha to Omicron: evolution of a transmembrane protein. mBio. 2023 Aug 31; 14(4):e0068823. PMID: 37477426.
- Published on 6/1/2023
Weingarten-Gabbay S, Chen DY, Sarkizova S, Taylor HB, Gentili M, Pearlman LR, Bauer MR, Rice CM, Clauser KR, Hacohen N, Carr SA, Abelin JG, Saeed M, Sabeti PC. The HLA-II immunopeptidome of SARS-CoV-2. bioRxiv. 2023 Jun 01. PMID: 37398281.
- Published on 5/29/2023
Yang L, Han Y, Zhou T, Lacko LA, Saeed M, Tan C, Danziger R, Zhu J, Zhao Z, Cahir C, Giani AM, Li Y, Dong X, Moroziewicz D, Paull D, Chen Z, Zhong A, Noggle SA, Rice CM, Qi Q, Evans T, Chen S. Isogenic human trophectoderm cells demonstrate the role of NDUFA4 and associated variants in ZIKV infection. iScience. 2023 Jul 21; 26(7):107001. PMID: 37534130.
- Published on 4/10/2023
Chen DY, Turcinovic J, Feng S, Kenney DJ, Chin CV, Choudhary MC, Conway HL, Semaan M, Close BJ, Tavares AH, Seitz S, Khan N, Kapell S, Crossland NA, Li JZ, Douam F, Baker SC, Connor JH, Saeed M. Cell culture systems for isolation of SARS-CoV-2 clinical isolates and generation of recombinant virus. iScience. 2023 May 19; 26(5):106634. PMID: 37095858.
- Published on 1/11/2023
Chen DY, Chin CV, Kenney D, Tavares AH, Khan N, Conway HL, Liu G, Choudhary MC, Gertje HP, O'Connell AK, Adams S, Kotton DN, Herrmann A, Ensser A, Connor JH, Bosmann M, Li JZ, Gack MU, Baker SC, Kirchdoerfer RN, Kataria Y, Crossland NA, Douam F, Saeed M. Spike and nsp6 are key determinants of SARS-CoV-2 Omicron BA.1 attenuation. Nature. 2023 Mar; 615(7950):143-150. PMID: 36630998.
- Published on 1/10/2023
Chen DY, Kenney D, Chin CV, Tavares AH, Khan N, Conway HL, Liu G, Choudhary MC, Gertje HP, O'Connell AK, Kotton DN, Herrmann A, Ensser A, Connor JH, Bosmann M, Li JZ, Gack MU, Baker SC, Kirchdoerfer RN, Kataria Y, Crossland NA, Douam F, Saeed M. Role of spike in the pathogenic and antigenic behavior of SARS-CoV-2 BA.1 Omicron. bioRxiv. 2023 Jan 10. PMID: 36263066.
- Published on 12/8/2022
Weingarten-Gabbay S, Pearlman LR, Chen DY, Klaeger S, Taylor HB, Welch NL, Keskin DB, Carr SA, Abelin JG, Saeed M, Sabeti PC. HLA-I immunopeptidome profiling of human cells infected with high-containment enveloped viruses. STAR Protoc. 2022 Dec 16; 3(4):101910. PMID: 36595954.
- Published on 12/7/2022
Torchia JA, Tavares AH, Carstensen LS, Chen DY, Huang J, Xiao T, Mukherjee S, Reeves PM, Tu H, Sluder AE, Chen B, Kotton DN, Bowen RA, Saeed M, Poznansky MC, Freeman GJ. Optimized ACE2 decoys neutralize antibody-resistant SARS-CoV-2 variants through functional receptor mimicry and treat infection in vivo. Sci Adv. 2022 Dec 09; 8(49):eabq6527. PMID: 36475798.
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