Abhishek Sharma (asharm16)

Abhishek Sharma

Associate Professor

Charles V. Schaefer, Jr. School of Engineering and Science

Department of Chemistry and Chemical Biology

Research

The overarching goal of Sharma lab is to design and develop novel-molecular reactivity and molecular function to ultimately accelerate the discovery of new therapeutics.

The emergence of resistance to chemotherapeutic drugs is a prominent challenge in the treatment of cancer as well as bacterial infections. In order to overcome this challenge, it is vital to not only develop drugs with novel mechanisms of action but also to expedite the chemical synthesis of these next generation anticancer and antibacterial agents. Some of our ongoing research projects are highlighted below.

We design, synthesize and evaluate mechanistically novel antiestrogens that can potently block the proliferative action of estrogen receptors in endocrine-therapy resistant breast cancer.
We are also interested in the design and development of small organic molecules that can inhibit protein-protein interactions or probe the physiological/pathological functions of biological receptors and enzymes.

Our another major focus area is the development of novel organoboron building blocks and synthetic methods that significantly expand the chemical space of bioactive molecules and protein conjugates. In a complementary approach, we seek to design new types of organoboron-based molecular probes to illuminate and modulate the biological function of disease-relevant proteins.


For more information: visit www.sharmalab.org

Publications(* = corresponding author)

After joining Stevens

38) Generation and application of alpha,alpha-diboryl radicals via thiyl radical catalyzed ring opening of vinyl cyclopropyl diborons: cis-Diastereoselective borylative cycloaddition with alkenes, H. Vyas, A. J. Gangani, A. Mini, S. Lin, J-M Chu, C. O. Agee, J. Gabriel, R. T. Williamson, Y. Zhang, A. Sharma,* Chem. Eur. J. 2023, (accepted). DOI: chem.202303175

37) SERDs: A case study in targeted protein degradation; L. Wang, A. Sharma,* Chem. Soc. Rev. 2022, 51, 8149-8159.
(Invited article, Part of two themed collections: “Modalities of induced proximity pharmacology: Degraders and Beyond” and "2022 emerging investigators")

36) Boron-promoted deprotonative conjugate addition: development of geminal diborons as versatile soft pronucleophiles and acyl anion equivalents; L. Wang, S. Lin, E. Santos, J. Pralat, K. Spotton, A. Sharma,* J. Org. Chem., 2022, 87, 9896-9906.

35) Acrylic boronate: a multifunctional C3 building block for catalytic synthesis of rare organoborons and chemoselective heterobifunctional ligations; S. Lin, L. Wang, A. Sharma,* Chemical Science, 2021, 12, 7924-7929.

34) Alpha-hydroxy boron-enabled regioselective access to bifunctional halo-boryl alicyclic ethers and alpha-halo borons; L. Wang, S. Lin, Y. Zhu, D. Ferrante, T. Ishak, Y. Baba, A. Sharma,* Chem. Commun. 2021, 57, 4564-4567.

33) The quest for orally available selective estrogen receptor degraders (SERDs); L. Wang, A. Sharma*, ChemMedChem, 2020, 15, 2072-2097. (Selected as a Very Important Paper (VIP) by the reviewers)

32) A modular and concise approach to MIDA acylboronates via chemoselective oxidation of unsymmetrical geminal diborylalkanes: Unlocking access to a novel class of acylborons; S. Lin, L. Wang, N. Aminoleslami, Y. Lao, C. Yagel, A. Sharma,* Chemical Science, 2019, 10, 4684-4691.

31) Antagonists for constitutively active mutant estrogen receptors: Insights into the roles of antiestrogen-core and side-chain; A. Sharma,* W. Toy, V. S. Guillen, N. Sharma, J. Min, K. E. Carlson, C. G. Mayne, S. Lin, M. Sabio, G. Greene, B. S. Katzenellenbogen, S. Chandarlapaty, J. A. Katzenellenbogen, ACS Chem. Biol. 2018, 2018, 13, 3374-3384.

30) New class of selective estrogen receptor degraders (SERDs): Expanding the toolbox of PROTAC degrons; L. Wang, V.S. Guillen, N. Sharma, K. Flessa, J. Min, K. E. Carlson, W. Toy, S. Braqi, B. S. Katzenellenbogen, J. A. Katzenellenbogen, S. Chandarlapaty, A. Sharma,* ACS Med. Chem. Lett. 2018, 9, 803-808.

29) Recent advances in the synthesis and synthetic applications of 1,2,3-triazoles; S. Lin, A. Sharma,* Chem. Heterocycl. Compd. 2018, 54, 314-316.

Before joining Stevens

28) Structurally novel antiestrogens elicit differential responses from constitutively active mutant estrogen receptors in breast cancer cells and tumors; Y. Zhao, M. J. Laws, V. S. Guillen, Y. Ziegler, J. Min, A. Sharma, S. H. Kim, D. Chu, B. H. Park, S. Oesterreich, C. Mao, D. J. Shapiro, K. W. Nettles, J. A. Katzenellenbogen, B. S. Katzenellenbogen, Cancer Res. 2017, 77, 5602-5613.

27) Adamantyl antiestrogens with novel side chains reveal a spectrum of activities in suppressing estrogen receptor mediated activities in breast cancer cells; J. Min, V. S. Guillen, A. Sharma, Y. Zhao, Y. Ziegler, P. Gong, C. G. Mayne, S. Srinivasan, S. H. Kim, K. E. Carlson, K. W. Nettles, B.S. Katzenellenbogen, J. A. Katzenellenbogen, J. Med. Chem. 2017, 60,6321-6336.

26) Exploring the structural compliancy versus specificity of the estrogen receptor using isomeric three-dimensional ligands; N. Sharma, K. Carlson, J. Nwachukwu, S. Srinivasan, A. Sharma, K. Nettles, J. A. Katzenellenbogen, ACS Chem. Biol. 2017, 12, 494-503.

25) Hydroxylated di- and tri-styrylbenzenes, a new class of antiplasmodial agents: discovery and mechanism of action; N. Sharma, D. Mohanakrishnan, A. Shard, A. Sharma, A. K. Sinha, D. A. Sahal, RSC Adv. 2016, 6, 49348-49357.

24) Insights into methyltransferase specificity and bioactivity of derivatives of the antibiotic plantazolicin; Y. Hao, P. M. Blair, A. Sharma, S. K. Nair, D. A. Mitchell; ACS Chem. Biol. 2015, 10, 1209-1216.

23) Triaryl-substituted schiff bases are high-affinity subtype-selective ligands for the estrogen receptor; Z.-Q. Liao, C. Dong, K. E. Carlson, S. Srinivasan, J. C. Nwachukwu, R. W. Chesnut, A. Sharma, K. W. Nettles, J.A. Katzenellenbogen, H.-B. Zhou; J. Med. Chem. 2014, 57, 3532-3545.

22) Synthesis of plantazolicin analogues enables dissection of ligand binding interactions of a highly selective methyltransferase; A. Sharma, P. M. Blair, D. A. Mitchell; Org. Lett. 2013, 15, 5076-5079.

21) Copper-catalyzed direct secondary and tertiary C-H alkylation of azoles through a novel Heteroarene-Amine-Aldehyde/Ketone coupling; D. Vachhani, A. Sharma, E. Van der Eycken; Angew. Chemie. Int. Ed. 2013, 52, 2547-2550.

20) Direct heteroarylation of tautomerizable heterocycles into unsymmetrical and symmetrical biheterocycles via Pd/Cu-catalyzed phosphonium coupling; A. Sharma, D. Vachhani, E. Van der Eycken; Org. Lett. 2012, 14, 1854-1857.

19) Developments in direct C-H arylation of (hetero)arenes under microwave irradiation; A. Sharma, D. Vachhani, E. Van der Eycken; Chem. Eur. J. 2013, 19, 1158-1168.

18) Pd/Cu-catalyzed C-H arylation of 1,3,4-thiadiazoles with (hetero)aryl iodides, bromides and triflates; D. Vachhani, A. Sharma, E. Van der Eycken; J. Org. Chem. 2012, 77, 8768–8774.

17) A facile diversity-oriented synthesis of imidazo[1,2-a]pyrazinones via gold-catalyzed regioselective heteroannulation of propynylaminopyrazinones; D. Vachhani, S. G. Modha, A. Sharma, E. Van der Eycken; Tetrahedron, 2013, 69, 359-365.

16) Microwave-assisted synthesis of medium-sized heterocycles; A. Sharma, P. Appukkuttan; Chem. Commun. 2012, 48, 1623-1637.

15) Direct olefination of benzaldehydes into hydroxy functionalized oligo-(p-phenylenevinylene)s via Pd-catalyzed heterodomino Knoevenagel-decarboxylation-Heck sequence and its application for fluoride sensing p-conjugated units; A. Sharma, N. Sharma, R. Kumar, A. Shard and A. K. Sinha, Chem. Commun. 2010, 46, 3283-3285.

14) Water promoted cascade rearrangement approach towards α-aryl aldehydes from arylalkenes using N-halosuccinimides: An avenue for asymmetric oxidation using phase transfer cinchona organocatalysis; A. Sharma, N. Sharma, R. Kumar, U. Sharma and A. K. Sinha, Chem. Commun. 2009, 5299-5301.

13) Tandem allylic oxidation-condensation/esterification catalyzed by silica gel: An expeditious approach towards antimalarial diaryldienones and enones from natural methoxylated phenylpropenes; A. Sharma, N. Sharma, A. Shard, R. Kumar, D. Mohankrishnan, A. K. Sinha and D. Sahal, Org. Biomol. Chem. 2011, 9, 5211-5219.

12) Unique versatility of ionic liquids as clean decarboxylation catalyst cum solvent: A metal and quinoline-free paradigm towards synthesis of indoles, styrenes, stilbenes and arene derivatives under microwave irradiation in aqueous conditions; A. Sharma, R. Kumar, N. Sharma, V. Kumar and A. K. Sinha, Adv. Synth. Catal. 2008, 350, 2910-2920.

11) Stilbene−chalcone hybrids: design, synthesis, and evaluation as a new class of antimalarial scaffolds that trigger cell death through stage specific apoptosis; N. Sharma, D. Mohanakrishnan, A. Shard, A. Sharma, Saima, A. K. Sinha and D. Sahal, J. Med. Chem. 2012, 55, 297-311.

10) Pd-catalyzed orthogonal Knoevenagel/Perkin-decarboxylation-Heck/Suzuki sequences: Tandem transformation of benzaldehydes into hydroxy functionalized antidiabetic stilbene-cinnamoyl hybrids and unsymmetrical distyrylbenzenes; N. Sharma, A. Sharma, R. Kumar, A. Shard, Saima and A. K. Sinha, Chem. Eur. J. 2011, 17, 10350-10356.

9) One-pot two-step oxidative cleavage of 1,2-arylalkenes to aryl ketones instead of arylaldehydes in an aqueous medium: A complementary approach to ozonolysis; N. Sharma, A. Sharma, R. Kumar, A. Shard and A. K. Sinha, Eur. J. Org. Chem. 2010, 6025-6032.

8) Reinvestigation of structure–activity relationship of methoxylated chalcones as antimalarials: Synthesis and evaluation of 2,4,5-trimethoxy substituted patterns as lead candidates derived from abundantly available natural β-asarone; R. Kumar, D. Mohanakrishnan, A. Sharma, N. K. Kaushik, K. Kalia, A. K. Sinha and D. Sahal, Eur. J. Med. Chem. 2010, 45, 5292-5301.

7) Metal-free activation of H2O2 by synergic effect of ionic liquid and microwave: chemoselective oxidation of benzylic alcohols to carbonyls and unexpected formation of anthraquinone in aqueous condition ; R. Kumar, N. Sharma, N. Sharma, A. Sharma, and A. K. Sinha, Mol. Divers.2011, 15, 687-695.

6) Green methodologies in synthesis and natural product chemistry of phenolic compounds, A. K. Sinha, N. Sharma, A. Shard, A. Sharma, R. Kumar and U. K. Sharma Ind. J. Chem.: Sec. B,2009, 48, 1771-1779.

5) Neutral ionic liquid [hmim]Br as a green reagent and solvent for mild and efficient dehydration of benzyl alcohols into (E)-arylalkenes under microwave irradiation, R. Kumar, A. Sharma, N. Sharma, V. Kumar and A. K. Sinha, Eur. J. Org. Chem. 2008, 5577-5582.

4) Microwave assisted efficient extraction of different parts of Hippophae rhamnoides for the comparative evaluation of antioxidant activity and quantification of its phenolic constituents by RP-HPLC; U. Sharma, K. Sharma, N. Sharma, A. Sharma, H.P. Singh and A.K. Sinha, J. Ag. Food Chem. 2008, 56, 374-379.

3) An unusual, mild and convenient one pot two step access to (E)-Stilbenes from hydroxyl substituted benzaldehydes and phenyl acetic acids under microwave activation: Revelation of new facet on the classical perkin reaction; A. K. Sinha, V. Kumar, A. Sharma, and A. Sharma, Tetrahedron, 2007, 63, 11070–11077.

2) DDQ catalyzed benzylic acetoxylation of arylalkanes: A case of exquisitely controlled oxidation under sonochemical activation; V. Kumar, A. Sharma, M. Sharma, U. Sharma and A. K. Sinha, Tetrahedron, 2007, 63, 9718–9723.

1) Remarkable synergism in methylimidazole-promoted decarboxylation of substituted cinnamic acid derivatives in basic water medium under microwave irradiation: A clean synthesis of hydroxylated (E)-stilbenes; V. Kumar, A. Sharma, A. Sharma and A. K. Sinha, Tetrahedron, 2007, 63, 7640–7646.

General Information

Research positions are available in the Sharma lab for motivated individuals:

Undergraduate and graduate students: Please send your CV and a cover letter describing your research and career interests to Dr. Sharma by email. You can also schedule a meeting with Dr. Sharma to learn more about our research.

Postdoctoral applicants: Please send your CV and a brief research summary describing your previous research.

Experience

Assistant Professor (11/2016-present), Stevens Institute of Technology

Postdoctoral Research Associate (2013-2016), University of Illinois at Urbana-Champaign - with Prof. John Katzenellenbogen

Postdoctoral Research Associate (2012-2013), University of Illinois at Urbana-Champaign - with Prof. Douglas A. Mitchell

FWO Postdoctoral Research Fellow (2011-2012), University of Leuven (KU Leuven), Belgium - with Prof. Erik Van der Eycken

Institutional Service

  • Graduate Student Admission Committee Member
  • PhD Program Coordinator Member
  • SES Doctoral Committee Member
  • CCB Faculty Search Committee Member
  • Academic Appeals Committee Member
  • SES Dean’s Faculty Advisory Council Member
  • CCB Department Chair Search Committee Member

Professional Service

  • Tetrahedron and Tetrahedron Letters Early Career Advisory Board

Honors and Awards

Susan G. Komen Early Career Fellowship - 2016

U.S. Department of Defense Breakthrough Award - 2018

Marie Curie Intra-European Postdoctoral Fellowship by European Union, (Not availed) - 2012

Postdoctoral Fellowship by the Research Foundation–Flanders (FWO), Belgium - 2010

Junior/Senior Research Fellowship (CSIR-NET JRF/SRF), India - 2006

Grants, Contracts and Funds

2016: Susan G. Komen Foundation Grant (Role: PI)

2019: U.S. Department of Defense Breakthrough Grant (Role: PI)

2020: NIH R15 grant (Role: PI)

2021: NSF REU/RET Site (Role: Collaborator)

2021: NIH MIRA (R35) grant (Role: PI)

Patents and Inventions

Patents

After joining Stevens

4) INK4 tumor suppressor proteins mediate resistance to CDK4/6 kinase inhibitors
S. Chandarlapaty, L. Qing, N. Gray, B, Jiang, A. Sharma, A. Mini (PCT application filed, 2022)

3) Antiestrogen compounds; A. Sharma, S. Chandarlapaty L. Wang, S. Lin, W. Toy, J. Katzenellenbogen (US 2021/0130320 A1)

Before joining Stevens

2) One-pot multicomponent synthesis of some novel hydroxy stilbene derivatives with α, β-carbonyl conjugation under microwave irradiation; A. Sharma, A. K. Sinha, R. Kumar, N. Sharma, (US8716532B2)

1) Microwave induced single step green synthesis of some novel 2-aryl aldehydes and their analogues; A. K. Sinha, A. Sharma, R. Kumar, N. Sharma, (US8981152B2).

Courses

CH 243
CH 244
CH 642
CH 115
CH 800