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.
Sebastian Kapell – Postdoctoral Associate
Hasahn Conway – Research Technician
Research positions are available, please contact Dr. Saeed.
- 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
- 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 Reports. 2018 Oct 23; 25(4): 833-840. (*First authors)
- 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. Nature Communications. 2018 May 29; 9(1): 2090.
- 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 Jr, Sacramento G, Nery N Jr, Orge C, Costa F, Reis MG, Thomas NM, Eisenreich T, Weinberger DM, de Almeida ARP, West AP Jr, 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 4;169(4): 597-609.
- 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 F, De Francesco R, Rice CM, Bartenschlager R, Lohmann V. Tuning a cellular lipid kinase activity adapts hepatitis C virus to replication in cell culture. Nature Microbiology. 2016 Dec 19; 2: 16247.
- 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.
- Stoddard MB, Li H, Wang S, Saeed M, Andrus L, Ding W, Jiang X, Learn GH, von Schaewen M, Wen J, Goepfert PA, Hahn BH, Ploss A, Rice CM, Shaw GM. Identification, molecular cloning, and analysis of full-length hepatitis C virus transmitted/founder genotypes 1, 3, and 4. MBio. 2015 Feb 24; 6(2).
- Wose Kinge CN, Espiritu C, Prabdial-Sing N, Sithebe NP, Saeed M*, Rice CM*. Hepatitis C virus genotype 5a subgenomic replicons for evaluation of direct-acting antiviral agents. Antimicrob Agents Chemother. 2014 Sep; 58(9): 5386-94. (*Corresponding authors)
- Rice CM, Saeed M. Hepatitis C: Treatment triumphs. Nature. 2014 Jun 5; 510(7503): 43-4.
- Liehl P, Zuzarte-Luís V, Chan J, Zillinger T, Baptista F, Carapau D, Konert M, Hanson KK, Carret C, Lassnig C, Müller M, Kalinke U, Saeed M, Chora AF, Golenbock DT, Strobl B, Prudêncio M, Coelho LP, Kappe SH, Superti-Furga G, Pichlmair A, Vigário AM, Rice CM, Fitzgerald KA, Barchet W, Mota MM. Host cell sensors for plasmodium activate innate immunity against liver stage infection. Nature Medicine. 2014 Jan; 20(1): 47-53.
- Saeed M, Scheel TK, Gottwein JM, Marukian S, Dustin LB, Bukh J, Rice CM. Efficient replication of genotype 3a and 4a hepatitis C virus replicons in human hepatoma cells. Antimicrob Agents Chemother. 2012 Oct; 56(10): 5365-73.
- Saeed M, Gondeau C, Hmwe S, Yokokawa H, Date T, Suzuki T, Kato T, Maurel P, Wakita T. Replication of Hepatitis C Virus Genotype 3a in Cell Culture. Gastroenterology. 2013 Jan; 144(1): 56-58.
- Saeed M, Suzuki R, Watanabe N, Masaki T, Tomonaga M, Muhammad A, Kato T, Matsuura Y, Watanabe H, Wakita T, Suzuki T. Role of the ERAD pathway in degradation of hepatitis C virus envelope proteins and production of virus particles. J Biol Chem. 2011 Oct 28; 286(43): 37264-73.
- Saeed M, Shiina M, Date T, Akazawa D, Watanabe N, Murayama A, Suzuki T, Watanabe H, Hiraga N, Imamura M, Chayama K, Choi Y, Krawczynski K, Liang TJ, Wakita T, Kato T. In vivo adaptation of hepatitis C virus in chimpanzees for efficient virus production and evasion of apoptosis. Hepatology. 2011 Aug; 54(2): 425-33.
- Masaki T, Suzuki R, Saeed M, Mori K, Matsuda M, Aizaki H, Ishii K, Maki N, Miyamura T, Matsuura Y, Wakita T, Suzuki T. Production of infectious hepatitis C virus by using RNA polymerase I-mediated transcription. J Virol. 2010 Jun; 84(11): 5824-35.
- Saeed M, Suzuki R, Kondo M, Aizaki H, Kato T, Mizuochi T, Wakita T, Watanabe H, Suzuki T. Evaluation of hepatitis C virus core antigen assays in detecting recombinant viral antigens of various genotypes. J Clin Microbiol. 2009 Dec; 47(12): 4141-3.
- Saeed M, Zaidi SZ, Naeem A, Masroor M, Sharif S, Shaukat S, Angez M, Khan A. Epidemiology and clinical findings associated with enteroviral acute flaccid paralysis in Pakistan. BMC Infect Dis. 2007 Feb 15; 7: 6.