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Akbar Ali PhD

TitleAssociate Professor
InstitutionUniversity of Massachusetts Medical School
DepartmentBiochemistry and Molecular Pharmacology
AddressUniversity of Massachusetts Medical School
364 Plantation Street, LRB
Worcester MA 01605
Phone508-856-8873
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    Other Positions
    InstitutionUMMS - School of Medicine
    DepartmentBiochemistry and Molecular Pharmacology


    Collapse Biography 
    Collapse education and training
    University of the Punjab, Lahore, , PakistanMSOrganic Chemistry
    Humboldt University Berlin, Berlin, , GermanyPHDOrganic Chemistry

    Collapse Overview 
    Collapse overview

    Targeting Drug Resistant Pathogens

    We are interested in understanding the mechanisms of drug resistance and developing strategies to design inhibitors with improved resistance profiles. Our lab uses medicinal chemistry approaches to target drug-resistant pathogens such as HIV and HCV, flaviviruses, and cancers.

    Research Focus

    Drug resistance is a major limitation in the treatment of pathogenic infections and cancers. Understanding the molecular mechanisms of drug resistance and developing strategies to avoid resistance could lead to more effective therapies against drug resistant pathogens. Under the leadership of Prof. Celia Schiffer, we focus on optimizing the resistance profile of HIV and HCV protease inhibitors by SBDD, organic synthesis, and structure-activity relationship (SAR) studies. Our lab is also interested in using fragment-based drug design (FBDD) to discover inhibitors against dengue, zika and other Flavivirus proteases.




    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Matthew AN, Leidner F, Newton A, Petropoulos CJ, Huang W, Ali A, KurtYilmaz N, Schiffer CA. Molecular Mechanism of Resistance in a Clinically Significant Double-Mutant Variant of HCV NS3/4A Protease. Structure. 2018 Aug 07. PMID: 30146168.
      View in: PubMed
    2. Rusere LN, Matthew AN, Lockbaum GJ, Jahangir M, Newton A, Petropoulos CJ, Huang W, Kurt Yilmaz N, Schiffer CA, Ali A. Quinoxaline-Based Linear HCV NS3/4A Protease Inhibitors Exhibit Potent Activity against Drug Resistant Variants. ACS Med Chem Lett. 2018 Jul 12; 9(7):691-696. PMID: 30034602.
      View in: PubMed
    3. Matthew AN, Zephyr J, Hill CJ, Jahangir M, Newton A, Petropoulos CJ, Huang W, Kurt Yilmaz N, Schiffer CA, Ali A. Hepatitis C Virus NS3/4A Protease Inhibitors Incorporating Flexible P2 Quinoxalines Target Drug Resistant Viral Variants. J Med Chem. 2017 Jun 08. PMID: 28594175.
      View in: PubMed
    4. Lin KH, Ali A, Rusere L, Soumana DI, Yilmaz NK, Schiffer CA. Dengue Virus NS2B/NS3 Protease Inhibitors Exploiting the Prime Side. J Virol. 2017 Mar 15. PMID: 28298600.
      View in: PubMed
    5. Soumana DI, Kurt Yilmaz N, Ali A, Prachanronarong KL, Schiffer CA. Molecular and Dynamic Mechanism Underlying Drug Resistance in Genotype 3 Hepatitis C NS3/4A Protease. J Am Chem Soc. 2016 Sep 14; 138(36):11850-9. PMID: 27512818.
      View in: PubMed
    6. Soumana DI, Kurt Yilmaz N, Prachanronarong KL, Aydin C, Ali A, Schiffer CA. Structural and Thermodynamic Effects of Macrocyclization in HCV NS3/4A Inhibitor MK-5172. ACS Chem Biol. 2016 Apr 15; 11(4):900-9. PMID: 26682473.
      View in: PubMed
    7. Sansó M, Levin RS, Lipp JJ, Wang VY, Greifenberg AK, Quezada EM, Ali A, Ghosh A, Larochelle S, Rana TM, Geyer M, Tong L, Shokat KM, Fisher RP. P-TEFb regulation of transcription termination factor Xrn2 revealed by a chemical genetic screen for Cdk9 substrates. Genes Dev. 2016 Jan 01; 30(1):117-31. PMID: 26728557.
      View in: PubMed
    8. Ndjomou J, Corby MJ, Sweeney NL, Hanson AM, Aydin C, Ali A, Schiffer CA, Li K, Frankowski KJ, Schoenen FJ, Frick DN. Simultaneously Targeting the NS3 Protease and Helicase Activities for More Effective Hepatitis C Virus Therapy. ACS Chem Biol. 2015 Aug 21; 10(8):1887-96. PMID: 25961497.
      View in: PubMed
    9. Soumana DI, Ali A, Schiffer CA. Structural analysis of asunaprevir resistance in HCV NS3/4A protease. ACS Chem Biol. 2014 Nov 21; 9(11):2485-90. PMID: 25243902.
      View in: PubMed
    10. Shen Y, Altman MD, Ali A, Nalam MN, Cao H, Rana TM, Schiffer CA, Tidor B. Testing the substrate-envelope hypothesis with designed pairs of compounds. ACS Chem Biol. 2013 Nov 15; 8(11):2433-41. PMID: 23952265.
      View in: PubMed
    11. Nalam MN, Ali A, Reddy GS, Cao H, Anjum SG, Altman MD, Yilmaz NK, Tidor B, Rana TM, Schiffer CA. Substrate envelope-designed potent HIV-1 protease inhibitors to avoid drug resistance. Chem Biol. 2013 Sep 19; 20(9):1116-24. PMID: 24012370.
      View in: PubMed
    12. Silver NW, King BM, Nalam MN, Cao H, Ali A, Kiran Kumar Reddy GS, Rana TM, Schiffer CA, Tidor B. Efficient Computation of Small-Molecule Configurational Binding Entropy and Free Energy Changes by Ensemble Enumeration. J Chem Theory Comput. 2013 Nov 12; 9(11):5098-5115. PMID: 24250277.
      View in: PubMed
    13. Fazly A, Jain C, Dehner AC, Issi L, Lilly EA, Ali A, Cao H, Fidel PL, Rao RP, Kaufman PD. Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis. Proc Natl Acad Sci U S A. 2013 Aug 13; 110(33):13594-9. PMID: 23904484.
      View in: PubMed
    14. Ali A, Aydin C, Gildemeister R, Romano KP, Cao H, Ozen A, Soumana D, Newton A, Petropoulos CJ, Huang W, Schiffer CA. Evaluating the role of macrocycles in the susceptibility of hepatitis C virus NS3/4A protease inhibitors to drug resistance. ACS Chem Biol. 2013 Jul 19; 8(7):1469-78. PMID: 23594083.
      View in: PubMed
    15. Romano KP, Ali A, Aydin C, Soumana D, Ozen A, Deveau LM, Silver C, Cao H, Newton A, Petropoulos CJ, Huang W, Schiffer CA. The molecular basis of drug resistance against hepatitis C virus NS3/4A protease inhibitors. PLoS Pathog. 2012; 8(7):e1002832. PMID: 22910833.
      View in: PubMed
    16. Parai MK, Huggins DJ, Cao H, Nalam MN, Ali A, Schiffer CA, Tidor B, Rana TM. Design, synthesis, and biological and structural evaluations of novel HIV-1 protease inhibitors to combat drug resistance. J Med Chem. 2012 Jul 26; 55(14):6328-41. PMID: 22708897.
      View in: PubMed
    17. Ali A, Wang J, Nathans RS, Cao H, Sharova N, Stevenson M, Rana TM. Synthesis and structure-activity relationship studies of HIV-1 virion infectivity factor (Vif) inhibitors that block viral replication. ChemMedChem. 2012 Jul; 7(7):1217-29. PMID: 22555953.
      View in: PubMed
    18. Li M, Shandilya SM, Carpenter MA, Rathore A, Brown WL, Perkins AL, Harki DA, Solberg J, Hook DJ, Pandey KK, Parniak MA, Johnson JR, Krogan NJ, Somasundaran M, Ali A, Schiffer CA, Harris RS. First-in-class small molecule inhibitors of the single-strand DNA cytosine deaminase APOBEC3G. ACS Chem Biol. 2012 Mar 16; 7(3):506-17. PMID: 22181350.
      View in: PubMed
    19. Romano KP, Ali A, Royer WE, Schiffer CA. Drug resistance against HCV NS3/4A inhibitors is defined by the balance of substrate recognition versus inhibitor binding. Proc Natl Acad Sci U S A. 2010 Dec 7; 107(49):20986-91. PMID: 21084633.
      View in: PubMed
    20. Ali A, Bandaranayake RM, Cai Y, King NM, Kolli M, Mittal S, Murzycki JF, Nalam MN, Nalivaika EA, Ozen A, Prabu-Jeyabalan MM, Thayer K, Schiffer CA. Molecular Basis for Drug Resistance in HIV-1 Protease. Viruses. 2010 Nov; 2(11):2509-35. PMID: 21994628.
      View in: PubMed
    21. Ali A, Reddy GS, Nalam MN, Anjum SG, Cao H, Schiffer CA, Rana TM. Structure-based design, synthesis, and structure-activity relationship studies of HIV-1 protease inhibitors incorporating phenyloxazolidinones. J Med Chem. 2010 Nov 11; 53(21):7699-708. PMID: 20958050.
      View in: PubMed
    22. O'Brien SK, Cao H, Nathans R, Ali A, Rana TM. P-TEFb kinase complex phosphorylates histone H1 to regulate expression of cellular and HIV-1 genes. J Biol Chem. 2010 Sep 24; 285(39):29713-20. PMID: 20551309.
      View in: PubMed
    23. Nalam MN, Ali A, Altman MD, Reddy GS, Chellappan S, Kairys V, Ozen A, Cao H, Gilson MK, Tidor B, Rana TM, Schiffer CA. Evaluating the substrate-envelope hypothesis: structural analysis of novel HIV-1 protease inhibitors designed to be robust against drug resistance. J Virol. 2010 May; 84(10):5368-78. PMID: 20237088.
      View in: PubMed
    24. Ali A, Ghosh A, Nathans RS, Sharova N, O'Brien S, Cao H, Stevenson M, Rana TM. Identification of flavopiridol analogues that selectively inhibit positive transcription elongation factor (P-TEFb) and block HIV-1 replication. Chembiochem. 2009 Aug 17; 10(12):2072-80. PMID: 19603446.
      View in: PubMed
    25. Jorissen RN, Reddy GS, Ali A, Altman MD, Chellappan S, Anjum SG, Tidor B, Schiffer CA, Rana TM, Gilson MK. Additivity in the analysis and design of HIV protease inhibitors. J Med Chem. 2009 Feb 12; 52(3):737-54. PMID: 19193159.
      View in: PubMed
    26. Nathans R, Cao H, Sharova N, Ali A, Sharkey M, Stranska R, Stevenson M, Rana TM. Small-molecule inhibition of HIV-1 Vif. Nat Biotechnol. 2008 Oct; 26(10):1187-92. PMID: 18806783.
      View in: PubMed
    27. Altman MD, Ali A, Reddy GS, Nalam MN, Anjum SG, Cao H, Chellappan S, Kairys V, Fernandes MX, Gilson MK, Schiffer CA, Rana TM, Tidor B. HIV-1 protease inhibitors from inverse design in the substrate envelope exhibit subnanomolar binding to drug-resistant variants. J Am Chem Soc. 2008 May 14; 130(19):6099-113. PMID: 18412349.
      View in: PubMed
    28. Reddy GS, Ali A, Nalam MN, Anjum SG, Cao H, Nathans RS, Schiffer CA, Rana TM. Design and synthesis of HIV-1 protease inhibitors incorporating oxazolidinones as P2/P2' ligands in pseudosymmetric dipeptide isosteres. J Med Chem. 2007 Sep 6; 50(18):4316-28. PMID: 17696512.
      View in: PubMed
    29. Chellappan S, Kiran Kumar Reddy GS, Ali A, Nalam MN, Anjum SG, Cao H, Kairys V, Fernandes MX, Altman MD, Tidor B, Rana TM, Schiffer CA, Gilson MK. Design of mutation-resistant HIV protease inhibitors with the substrate envelope hypothesis. Chem Biol Drug Des. 2007 May; 69(5):298-313. PMID: 17539822.
      View in: PubMed
    30. Ali A, Reddy GS, Cao H, Anjum SG, Nalam MN, Schiffer CA, Rana TM. Discovery of HIV-1 protease inhibitors with picomolar affinities incorporating N-aryl-oxazolidinone-5-carboxamides as novel P2 ligands. J Med Chem. 2006 Dec 14; 49(25):7342-56. PMID: 17149864.
      View in: PubMed
    31. Chiu YL, Dinesh CU, Chu CY, Ali A, Brown KM, Cao H, Rana TM. Dissecting RNA-interference pathway with small molecules. Chem Biol. 2005 Jun; 12(6):643-8. PMID: 15975509.
      View in: PubMed
    32. Chiu YL, Ali A, Chu CY, Cao H, Rana TM. Visualizing a correlation between siRNA localization, cellular uptake, and RNAi in living cells. Chem Biol. 2004 Aug; 11(8):1165-75. PMID: 15324818.
      View in: PubMed
    33. Hwang S, Tamilarasu N, Kibler K, Cao H, Ali A, Ping YH, Jeang KT, Rana TM. Discovery of a small molecule Tat-trans-activation-responsive RNA antagonist that potently inhibits human immunodeficiency virus-1 replication. J Biol Chem. 2003 Oct 3; 278(40):39092-103. PMID: 12857725.
      View in: PubMed
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