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Akbar Ali PhD

TitleAssociate Professor
InstitutionUMass Chan Medical School
DepartmentBiochemistry and Molecular Biotechnology
AddressUMass Chan Medical School
364 Plantation Street LRB
Worcester MA 01605
Phone508-856-8873
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    Other Positions
    InstitutionT.H. Chan School of Medicine
    DepartmentBiochemistry and Molecular Biotechnology


    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.
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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Arya R, Maben Z, Rane D, Ali A, Stern LJ. Phenylsulfamoyl Benzoic Acid Inhibitor of ERAP2 with a Novel Mode of Inhibition. ACS Chem Biol. 2022 07 15; 17(7):1756-1768. PMID: 35767698.
      Citations:    Fields:    Translation:Cells
    2. Zephyr J, Nageswara Rao D, Vo SV, Henes M, Kosovrasti K, Matthew AN, Hedger AK, Timm J, Chan ET, Ali A, Kurt Yilmaz N, Schiffer CA. Deciphering the Molecular Mechanism of HCV Protease Inhibitor Fluorination as a General Approach to Avoid Drug Resistance. J Mol Biol. 2022 05 15; 434(9):167503. PMID: 35183560.
      Citations:    Fields:    Translation:HumansCells
    3. Nageswara Rao D, Zephyr J, Henes M, Chan ET, Matthew AN, Hedger AK, Conway HL, Saeed M, Newton A, Petropoulos CJ, Huang W, Kurt Yilmaz N, Schiffer CA, Ali A. Discovery of Quinoxaline-Based P1-P3 Macrocyclic NS3/4A Protease Inhibitors with Potent Activity against Drug-Resistant Hepatitis C Virus Variants. J Med Chem. 2021 08 26; 64(16):11972-11989. PMID: 34405680.
      Citations: 3     Fields:    Translation:AnimalsCells
    4. Lockbaum GJ, Henes M, Talledge N, Rusere LN, Kosovrasti K, Nalivaika EA, Somasundaran M, Ali A, Mansky LM, Kurt Yilmaz N, Schiffer CA. Inhibiting HTLV-1 Protease: A Viable Antiviral Target. ACS Chem Biol. 2021 03 19; 16(3):529-538. PMID: 33619959.
      Citations: 4     Fields:    Translation:HumansCells
    5. Lockbaum GJ, Reyes AC, Lee JM, Tilvawala R, Nalivaika EA, Ali A, Kurt Yilmaz N, Thompson PR, Schiffer CA. Crystal Structure of SARS-CoV-2 Main Protease in Complex with the Non-Covalent Inhibitor ML188. Viruses. 2021 01 25; 13(2). PMID: 33503819.
      Citations: 22     Fields:    Translation:Cells
    6. Matthew AN, Leidner F, Lockbaum GJ, Henes M, Zephyr J, Hou S, Rao DN, Timm J, Rusere LN, Ragland DA, Paulsen JL, Prachanronarong K, Soumana DI, Nalivaika EA, Kurt Yilmaz N, Ali A, Schiffer CA. Drug Design Strategies to Avoid Resistance in Direct-Acting Antivirals and Beyond. Chem Rev. 2021 03 24; 121(6):3238-3270. PMID: 33410674.
      Citations: 6     Fields:    Translation:HumansCells
    7. Ibrahim M, Latif A, Ali A, Ribeiro AI, Farooq U, Ullah F, Khan A, Al-Harrasi A, Ahmad M, Ali M. Macrocyclic sulfone derivatives: Synthesis, characterization, in vitro biological evaluation and molecular docking. Drug Dev Res. 2021 06; 82(4):562-574. PMID: 33368483.
      Citations: 1     Fields:    Translation:Cells
    8. Rusere LN, Lockbaum GJ, Henes M, Lee SK, Spielvogel E, Rao DN, Kosovrasti K, Nalivaika EA, Swanstrom R, Kurt Yilmaz N, Schiffer CA, Ali A. Structural Analysis of Potent Hybrid HIV-1 Protease Inhibitors Containing Bis-tetrahydrofuran in a Pseudosymmetric Dipeptide Isostere. J Med Chem. 2020 08 13; 63(15):8296-8313. PMID: 32672965.
      Citations: 1     Fields:    Translation:HumansCells
    9. Matthew AN, Zephyr J, Nageswara Rao D, Henes M, Kamran W, Kosovrasti K, Hedger AK, Lockbaum GJ, Timm J, Ali A, Kurt Yilmaz N, Schiffer CA. Avoiding Drug Resistance by Substrate Envelope-Guided Design: Toward Potent and Robust HCV NS3/4A Protease Inhibitors. mBio. 2020 03 31; 11(2). PMID: 32234812.
      Citations: 7     Fields:    Translation:HumansCells
    10. Timm J, Kosovrasti K, Henes M, Leidner F, Hou S, Ali A, Kurt Yilmaz N, Schiffer CA. Molecular and Structural Mechanism of Pan-Genotypic HCV NS3/4A Protease Inhibition by Glecaprevir. ACS Chem Biol. 2020 02 21; 15(2):342-352. PMID: 31868341.
      Citations: 4     Fields:    Translation:Cells
    11. Maben Z, Arya R, Rane D, An WF, Metkar S, Hickey M, Bender S, Ali A, Nguyen TT, Evnouchidou I, Schilling R, Stratikos E, Golden J, Stern LJ. Discovery of Selective Inhibitors of Endoplasmic Reticulum Aminopeptidase 1. J Med Chem. 2020 01 09; 63(1):103-121. PMID: 31841350.
      Citations: 9     Fields:    Translation:HumansCells
    12. Rusere LN, Lockbaum GJ, Lee SK, Henes M, Kosovrasti K, Spielvogel E, Nalivaika EA, Swanstrom R, Yilmaz NK, Schiffer CA, Ali A. HIV-1 Protease Inhibitors Incorporating Stereochemically Defined P2' Ligands To Optimize Hydrogen Bonding in the Substrate Envelope. J Med Chem. 2019 09 12; 62(17):8062-8079. PMID: 31386368.
      Citations: 7     Fields:    Translation:HumansCells
    13. Lockbaum GJ, Leidner F, Rusere LN, Henes M, Kosovrasti K, Nachum GS, Nalivaika EA, Bolon DNA, Ali A, Kurt Yilmaz N, Schiffer CA. Correction to Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. ACS Infect Dis. 2019 Jun 14; 5(6):1044. PMID: 30990653.
      Citations:    Fields:    
    14. Lockbaum GJ, Leidner F, Rusere LN, Henes M, Kosovrasti K, Nachum GS, Nalivaika EA, Ali A, Yilmaz NK, Schiffer CA. Structural Adaptation of Darunavir Analogues against Primary Mutations in HIV-1 Protease. ACS Infect Dis. 2019 02 08; 5(2):316-325. PMID: 30543749.
      Citations: 11     Fields:    Translation:HumansCells
    15. 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 10 02; 26(10):1360-1372.e5. PMID: 30146168.
      Citations: 10     Fields:    Translation:HumansCells
    16. 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.
      Citations:    
    17. 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 07 13; 60(13):5699-5716. PMID: 28594175.
      Citations: 10     Fields:    Translation:HumansCells
    18. Lin KH, Ali A, Rusere L, Soumana DI, Kurt Yilmaz N, Schiffer CA. Dengue Virus NS2B/NS3 Protease Inhibitors Exploiting the Prime Side. J Virol. 2017 05 15; 91(10). PMID: 28298600.
      Citations: 13     Fields:    Translation:HumansCells
    19. 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 09 14; 138(36):11850-9. PMID: 27512818.
      Citations: 25     Fields:    Translation:Cells
    20. 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.
      Citations: 15     Fields:    
    21. 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.
      Citations: 55     Fields:    Translation:HumansCells
    22. 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.
      Citations: 2     Fields:    Translation:HumansCells
    23. 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.
      Citations: 21     Fields:    Translation:Cells
    24. 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.
      Citations: 13     Fields:    Translation:HumansCells
    25. 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.
      Citations: 25     Fields:    Translation:HumansCells
    26. 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.
      Citations: 12     Fields:    
    27. 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.
      Citations: 53     Fields:    Translation:HumansAnimalsCells
    28. 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.
      Citations: 27     Fields:    Translation:HumansCells
    29. 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.
      Citations: 74     Fields:    Translation:HumansCells
    30. 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.
      Citations: 6     Fields:    Translation:Cells
    31. 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.
      Citations: 20     Fields:    Translation:HumansCells
    32. 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.
      Citations: 73     Fields:    Translation:HumansCells
    33. 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 07; 107(49):20986-91. PMID: 21084633.
      Citations: 82     Fields:    Translation:HumansCells
    34. Ali A, Bandaranayake RM, Cai Y, King NM, Kolli M, Mittal S, Murzycki JF, Nalam MNL, Nalivaika EA, Özen A, Prabu-Jeyabalan MM, Thayer K, Schiffer CA. Molecular Basis for Drug Resistance in HIV-1 Protease. Viruses. 2010 Nov; 2(11):2509-2535. PMID: 21994628.
      Citations: 52     Fields:    
    35. 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.
      Citations: 16     Fields:    Translation:HumansCells
    36. 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.
      Citations: 15     Fields:    Translation:HumansCells
    37. 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.
      Citations: 59     Fields:    Translation:HumansCells
    38. 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.
      Citations: 17     Fields:    Translation:HumansCells
    39. 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.
      Citations: 9     Fields:    Translation:Cells
    40. 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.
      Citations: 98     Fields:    Translation:HumansCells
    41. 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.
      Citations: 43     Fields:    Translation:Cells
    42. 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 06; 50(18):4316-28. PMID: 17696512.
      Citations: 14     Fields:    Translation:HumansCells
    43. 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.
      Citations: 25     Fields:    
    44. 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.
      Citations: 26     Fields:    Translation:Cells
    45. 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.
      Citations: 15     Fields:    Translation:HumansCells
    46. 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.
      Citations: 115     Fields:    Translation:HumansCells
    47. 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 03; 278(40):39092-103. PMID: 12857725.
      Citations: 31     Fields:    Translation:HumansAnimalsCells
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