Siddik Sarkar , Ph.D.

Senior Scientist, Asst. Professor (AcSIR)
Cancer Biology & Inflammatory Disorder
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Research Interest

Research interest: 

Cancer is a dynamic disease and further added miseries due to inter- and intra- cellular heterogeneity. The heterogeneity in spatial locations of different populations of cells help us in identifying the involvement of infiltrating T cell in cancer prognosis. In recent past immunotherapy specifically immune-checkpoint inhibition has emerged as one of the most potent treatment option in melanoma and liquid malignancy (leukemia), but success is limited in solid tumor malignancy. In our laboratory, we are focusing on developing next generation immunotherapeutic that could target the immune surveillance pathways, immune check points, and activate the immune system in general and T cells or NK cells in particular, eventually leading to cancer cell killing in solid tumors. Cancer cells escape immune surveillance not only by upregulating immune check points, but also by downregulating MHC/ HLA molecules and hence antigen presentation pathways are inhibited. In this regard, we are developing chimeric antigen receptor T/ NK (CAR-T/ CAR-NK) targeting neo-antigens or cancer surface markers that induce cancer cell killing independent of MHC expression. The overall objective of the laboratory is to find and identify biomarkers that could be eventually targeted by developing different types of biologics. These biologics would effectively kill the cancer cells and increase the overall survival of cancer patients pertaining to solid tumor malignancy of breast and ovary. The current area of work: -

• Developing vectors (Adeno- and lenti- viral based) for efficient gene transfer

• Armed oncolytic Adenovirus 

• Recombinant chimeric or small size antibodies (nanobody) fused with antitumor cytokines for cancer immunotherapy

• Developing effective bi-specific CAR-T or CAR-NK based therapy for breast and ovarian cancer

• Novel cancer biomarkers that can be targeted for developing cancer immuno- or chemo- therapeutics

Credentials

  • PhD (2006-2010) in Breast cancer and molecular targeted therapy, INDIAN INSTITUTE OF TECHNOLOGY (IIT) KHARAGPUR, WB, INDIA
  • Postdoctoral Research (2010-2015) in the Development of viral immune-gene therapy and molecular imaging in cancer detection and prognosis – VIRGINIA COMMONWEALTH UNIVERSITY (VCU), MCV Campus, Richmond, VA, US
  • Postdoctoral Associate Scientist (2015-2017) in cancer gene therapy and imaging – RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY, NJ, US

Honours & Awards

  • 2016-2017: Received 1 year (2016-2017) research grant (An Effective Chemotherapeutic Approach for Ovarian Cancer Intraperitoneal Metastasis) sponsored by New Jersey Health Foundation. Amount: $ 40,000. Role: Co-PI.
  • 2017: Received Gallo Award for scientific excellence presented by Rutgers Cancer Institute of New Jersey for outstanding cancer research “Combination therapy using SN38 and MMAE to kill cancer stem cell-rich ovarian ascites” (May 2017).
  • 2016: Received Gallo Award for scientific excellence presented by Rutgers Cancer Institute of New Jersey for outstanding cancer research “ Development of therapeutic protocol for drug resistant ovarian cancer” (May 2016).
  • 2011-2013: Received 2 years Postdoctoral fellowship grant (Award Number: W81XWH-11-1-0186. Developing an Effective Therapy for Prostate Cancer. Funding Mechanism: Prostate Cancer Training Award – Postdoctoral – Ph.D or M.D. Award Amount: $116,020.00.) sponsored by U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland, US.
  • 2013: Received Travel grant from Department of Defense, U.S. Army Medical Research and Materiel Command to attend the Annual Meeting 2013 held at Washington DC organized by American Association for Cancer Research.
  • 2009: Received Travel grant from Department of Biotechnology, India and also from Indian Institute of Technology Kharagpur, India to attend the international symposium “ VIII Madrid Breast Cancer Conference”, Madrid, Spain (June 2009).

Grants & Supports

  1. Genomic Surveillance program for SARS-CoV-2: Consortium of India and Sri Lanka (Ref: 223547/Z/21/Z Dated: 24.01.2022). Funding Agency: The Wellcome Trust, UK. Role: PI. Tenure: 2022-2023
  2. Pan-CSIR Cancer Research Program “Making Cancer Care Affordable” Empowering Women’s Health: Focusing on Breast and Gynecological Cancers of Indian Relevance. Subtheme. Development of immunothereapeutics targeting breast and ovarian cancer (Project Code: HCP-40). Funding Agency: CSIR. Tenure: 2021-2026
  3. Modern innovative solutions for Occupational Lung Health challenges in human (MLP137). Funding Agency: CSIR.  Tenure: 2021-  
  4. Suicidal gene therapy using engineered secretory carboxylesterse-2/ Camptothecin-11 targeting chemoresistant ovarian serous adenocarcinoma.  Funding Agency: Science and Engineering Research Board (SERB): File. SRG/2019/001880) Role: PI. Tenure: 2019-2022 
  5. Noninvasive Magnetoacoustics Stimulation in Cancer Therapeutics and Delivery (File. (IP1-SS/611) Intramural CSIR-IICB. Role PI. Tenure: 2022-
  6. Molecular digital Surveillance of COVID-19 samples at IICB (Whole genome sequencing of COVID-19 samples; MLP-132): Intramural-CSIR. Tenure (2021-2022)
  7. Sentinel site for Indian SARS-CoV-2 Genomics Consortium (INSACOG):  Genomics & Molecular Surveillance of SARS-COV-2: Funding Agency: Jointly supported by DBT, CSIR, National Center for Disease Control and Public Health (Head quarter: Georgia, US)

 

Patents & Publications

Publications
  1. Sarkar P, Banerjee S, Saha SA, Mitra P, Sarkar S*. Genome surveillance of SARS-CoV-2 variants and their role in pathogenesis focusing on second wave of COVID-19 in India. Scientific Reports 13, 4692 (2023). PMID: 36949118. DOI: 10.1038/s41598-023-30815-5.
  2. Sarkar P, Banerjee S, Chakrabarti S, Chakrabarti P, Bandyopadhyay A, Ghosh AM, Saha S, Roy A, Sarkar S. Genome characterization, phylogenomic assessment and spatio-temporal dynamics study of highly mutated BA variants from India. Indian J Med Microbiol. (Elsevier). 2022; S0255-0857(22)00232-8. PMID: 36400646. doi: 10.1016/j.ijmmb.2022.10.006
  3. Chandra Jena B, Sarkar S, Rout L, Mandal M. The transformation of cancer-associated fibroblasts: Current perspectives on the role of TGF-β in CAF mediated tumor progression and therapeutic resistance. Cancer Lett. 2021 Nov 1; 520:222-232. doi: 10.1016/j.canlet.2021.08.002. Epub 2021 Aug 5. PMID: 34363903.
  4. Basu D, Chakraborty S, Pal R, Sharma TK, Sarkar S*. Identification and Engineering of Aptamers for Theranostic Application in Human Health and Disorders. Int J Mol Sci. 2021 Sep 7; 22(18):9661. doi: 10.3390/ijms22189661. PMID: 34575825; PMCID: PMC8469434.
  5. Gaur V, Chaudhary S, Tyagi A, Agarwal S, Sharawat SK, Sarkar S, Singh H, Bakhshi S, Sharma P, Kumar S. Dysregulation of miRNA expression and their prognostic significance in paediatric cytogenetically normal acute myeloid leukaemia. Br J Haematol. 2020 Mar;188(6):e90-e94. PubMed PMID: 32077100.
  6. Malekshah OM, Sarkar S, Nomani A, Patel N, Javidian P, Goedken M, Polunas M, Louro P, Hatefi A. Bioengineered adipose-derived stem cells for targeted enzyme-prodrug therapy of ovarian cancer intraperitoneal metastasis. J Control Release. 2019 Oct;311-312:273-287. PubMed PMID: 31499084.
  7. Sarkar S, Malekshah OM, Nomani A, Patel N, Hatefi A. A novel chemotherapeutic protocol for peritoneal metastasis and inhibition of relapse in drug resistant ovarian cancer. Cancer Med. 2018 Aug;7(8):3630-3641. PMID: 29926538
  8. Kumar BNP, Puvvada N, Rajput S, Sarkar S, Mahto MK, Yallapu MM, Pathak A, Emdad L, Das SK, Reis RL, Kundu SC, Fisher PB, Mandal M. Targeting of EGFR, VEGFR2 and Akt by engineered dual drug encapsulated mesoporous silica-gold nanoclusters sensitizes tamoxifen-resistant breast cancer. Mol Pharm. 2018 Jul 2;15(7):2698-2713.PMID: 29787277
  9. Sarkar S*, Konar S, Prasad PN, Rajput S, Kumar BNP, et al. Micellear Gold Nanoparticles as Delivery Vehicles for Dual Tyrosine Kinase Inhibitor ZD6474 for Metastatic Breast Cancer Treatment. Langmuir. 2017 Aug 8;33(31):7649-7659. PubMed PMID: 28701038. (Corresponding author)
  10. Malekshah OM, Chen X, Nomani A, Sarkar S, Hatefi A. Enzyme/Prodrug Systems for Cancer Gene Therapy. Curr Pharmacol Rep. 2016 Dec;2(6):299-308. PubMed PMID: 28042530
  11. Bhutia SK, Behera B, Das DN, Mukhopadhyay S, Sinha N, Panda PK, Naik PP, Patra SK, Mandal M, Sarkar S, Menezes ME, Talukdar S, Maiti TK, Das SK, Sarkar D, Fisher PB. Abrus agglutinin is a potent anti-proliferative and anti-angiogenic agent in human breast cancer. Int J Cancer. 2016 Jul 15;139(2):457-66. PubMed PMID: 26914517.
  12. Sarkar S, Pradhan A, Das S, Emdad L, Sarkar D, Pellecchia M, Fisher PB. Novel therapy of prostate cancer employing a combination of viral-based immunotherapy and a small molecule BH3 mimetic. Oncoimmunology. 2016 Mar;5(3):e1078059. PubMed PMID: 27141334.
  13. Rajput S, Puvvada N, Kumar BN, Sarkar S, Konar S, Bharti R, Dey G, Mazumdar A, Pathak A, Fisher PB, Mandal M. Overcoming Akt Induced Therapeutic Resistance in Breast Cancer through siRNA and Thymoquinone Encapsulated Multilamellar Gold Niosomes. Mol Pharm. 2015 Dec 7;12(12):4214-25. PubMed PMID: 26505213.
  14. Kumar BN, Puvvada N, Rajput S, Sarkar S, Venkatesan P, Pal I, Dey G, Konar S, Mazumdar A, Kundu SC, Pathak A, Fisher PB, Mandal M. Sequential release of tamoxifen and diosgenin from hollow manganese ferrate nanocarriers for breast cancer treatment. Journal of Materials Chemistry B. 2015 October 06; 3:90-101.
  15. PuvvadaN, Rajput S, Kumar BN, Sarkar S, Konar S, Brunt KR, Rao R, Mazumdar A, Das, SK, Basu R, Fisher PB, Mandal M, Pathak A. Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression. Sci Rep. 2015 Jul 6;5:11760. PubMed PMID: 26145450
  16. Das P, Sarkar S, Mandal M, Sen R. Green surfactant of marine origin exerting a cytotoxic effect on cancer cell lines. RSC advances. 2015 June 10; 5:53086-53094.
  17. Quinn BA, Dash R, Sarkar S, Azab B, Bhoopathi P, Das SK, Emdad L, Wei J, Pellecchia M, Sarkar D, Fisher PB. Pancreatic Cancer Combination Therapy Using a BH3 Mimetic and a Synthetic Tetracycline. Cancer Res. 2015 Jun 1;75(11):2305-15. PubMed PMID: 26032425
  18. Sarkar S, Quinn BA, Shen X-N, Dash R, Das SK, Emdad L, Klibanov AL, Wang X-Y, Pellecchia M, Sarkar D, Fisher PB. Therapy of prostate cancer using a novel cancer terminator virus and a small molecule BH-3 mimetic. Oncotarget. 2015 May 10;6(13):10712-27. PubMed PMID: 25926554
  19. Sarkar S, Quinn BA, Shen X, Dent P, Das SK, Emdad L, Sarkar D, Fisher PB. Reversing translational suppression and induction of toxicity in pancreatic cancer cells using a chemoprevention gene therapy approach. Mol Pharmacol. 2015 Feb;87(2):286-95. PubMed PMID: 25452327
  20. Dey KK, Sarkar S, Pal I, Das S, Dey G, Bharti R, Banik P, Ray JG, Maity S, Kulavi I, Mandal M. Mechanistic attributes of S100A7 (psoriasin) in resistance of anoikis resulting tumor progression in squamous cell carcinoma of the oral cavity. Cancer Cell Int. 2015;15:74. PubMed PMID: 26225121
  21. Bhatnagar A, Wang Y, Mease R, Gabrielson M, Sysa P, Minn I, Green G, Simmons B, Gabrielson K, Sarkar S, Fisher PB, Pomper M.. AEG-1 promoter-mediated imaging of prostate cancer. Cancer Res. 2014 Oct 15;74(20):5772-81. PubMed PMID: 25145668
  22. Pal I, Sarkar S, Rajput S, Dey KK, Chakraborty S, Dash R, Das SK, Sarkar D, Barile E, De S, Pellecchia M, Fisher PB, Mandal M. BI-69A11 enhances susceptibility of colon cancer cells to mda-7/IL-24-induced growth inhibition by targeting Akt. Br J Cancer. 2014 Jul 8;111(1):101-11. PubMed PMID: 24892445
  23. Dash R, Bhoopathi P, Das SK, Sarkar S, Emdad L, et al. Novel mechanism of MDA-7/IL-24 cancer-specific apoptosis through SARI induction. Cancer Res. 2014 Jan 15;74(2):563-74. PubMed PMID: 24282278
  24. Sarkar S, Azab B, Quinn BA, Shen X, Dent P, et al. Chemoprevention gene therapy (CGT) of pancreatic cancer using perillyl alcohol and a novel chimeric serotype cancer terminator virus. Curr Mol Med. 2014 Jan;14(1):125-40. PubMed PMID: 24236457.
  25. Azab BM, Dash R, Das SK, Bhutia SK, Sarkar S, Shen XN, Quinn BA, Dent P, Dmitriev IP, Wang XY, Curiel DT, Pellecchia M, Reed JC, Sarkar D, Fisher PB. Enhanced prostate cancer gene transfer and therapy using a novel serotype chimera cancer terminator virus (Ad5/3-CTV). J Cell Physiol. 2014 Jan;229(1):34-43. PubMed PMID: 23868767
  26. Sarkar S, Rajput S, Tripathi AK, Mandal M. Targeted therapy against EGFR and VEGFR using ZD6474 enhances the therapeutic potential of UV-B phototherapy in breast cancer cells. Mol Cancer. 2013 Oct 20;12(1):122. PubMed PMID: 24138843
  27. Sarkar S, Azab BM, Das SK, Quinn BA, Shen X, et al. Chemoprevention gene therapy (CGT): novel combinatorial approach for preventing and treating pancreatic cancer. Curr Mol Med. 2013 Aug;13(7):1140-59. PubMed PMID: 23157679.
  28. Rajput S, Kumar BN, Sarkar S, Das S, Azab B, Santhekadur PK, Das SK, Emdad L, Sarkar D, Fisher PB, Mandal M. Targeted apoptotic effects of thymoquinone and tamoxifen on XIAP mediated Akt regulation in breast cancer. PLoS One. 2013;8(4):e61342. PubMed PMID: 23613836
  29. Hedvat M, Emdad L, Das SK, Kim K, Dasgupta S, Thomas S, Hu B, Zhu S, Dash R, Quinn BA, Oyesanya RA, Kegelman TP, Sokhi UK, Sarkar S, Erdogan E, Menezes ME, Bhoopathi P, Wang XY, Pomper MG, Wei J, Wu B, Stebbins JL, Diaz PW, Reed JC, Pellecchia M, Sarkar D, Fisher PB. Selected approaches for rational drug design and high throughput screening to identify anti-cancer molecules. Anticancer Agents Med Chem. 2012 Nov;12(9):1143-55. PubMed PMID: 22931411
  30. Azab BM, Dash R, Das SK, Bhutia SK, Shen XN, Quinn BA, Sarkar S, Wang XY, Hedvat M, Dmitriev IP, Curiel DT, Grant S, Dent P, Reed JC, Pellecchia M, Sarkar D, Fisher PB. Enhanced delivery of mda-7/IL-24 using a serotype chimeric adenovirus (Ad5/3) in combination with the Apogossypol derivative BI-97C1 (Sabutoclax) improves therapeutic efficacy in low CAR colorectal cancer cells. J Cell Physiol. 2012 May;227(5):2145-53. PubMed PMID: 21780116
  31. Quinn BA, Dash R, Azab B, Sarkar S, Das SK, Kumar S, Oyesanya RA, Dasgupta S, Dent P, Grant S, Rahmani M, Curiel DT, Dmitriev I, Hedvat M, Wei J, Wu B, Stebbins JL, Reed JC, Pellecchia M, Sarkar D, Fisher PB. Targeting Mcl-1 for the therapy of cancer. Expert Opin Investig Drugs. 2011 Oct;20(10):1397-411. PubMed PMID: 21851287
  32. Sarkar S, Mazumdar A, Dash R, Sarkar D, Fisher PB, Mandal M. ZD6474 enhances paclitaxel antiproliferative and apoptotic effects in breast carcinoma cells. J Cell Physiol. 2011 Feb;226(2):375-84. PubMed PMID: 20665703.
  33. Sethi K, Sarkar S, Das S, Rajput S, Mazumder A, Roy B, Patra S, Mohanty B, El-Naggar AK, Mandal M. Expressions of CK-19, NF-kappaB, E-cadherin, beta-catenin and EGFR as diagnostic and prognostic markers by immunohistochemical analysis in thyroid carcinoma. J Exp Ther Oncol. 2011;9(3):187-99. PubMed PMID: 22070050.
  34. Dash R, Azab B, Shen XN, Sokhi UK, Sarkar S, Su ZZ, Wang XY, Claudio PP, Dent P, Dmitriev IP, Curiel DT, Grant S, Sarkar D, Fisher PB. Developing an effective gene therapy for prostate cancer: New technologies with potential to translate from the laboratory into the clinic. Discov Med. 2011 Jan;11(56):46-56. PubMed PMID: 21276410
  35. Thakur G, Mitra A, Rousseau D, Basak A, Sarkar S, Pal K. Crosslinking of gelatin-based drug carriers by genipin induces changes in drug kinetic profiles in vitro. J Mater Sci Mater Med. 2011 Jan;22(1):115-23. PubMed PMID: 21107660.
  36. Sarkar S, Mazumdar A, Dash R, Sarkar D, Fisher PB, Mandal M. ZD6474, a dual tyrosine kinase inhibitor of EGFR and VEGFR-2, inhibits MAPK/ERK and AKT/PI3-K and induces apoptosis in breast cancer cells. Cancer Biol Ther. 2010 Apr 15;9(8):592-603. PubMed PMID: 20139705.
  37. Sethi K, Sarkar S, Das S, Mohanty B, Mandal M. Biomarkers for the diagnosis of thyroid cancer. J Exp Ther Oncol. 2010;8(4):341-52. PubMed PMID: 21222366.
  38. Sarkar S, Mandal M. Growth factor receptors and apoptosis regulators: signaling pathways, prognosis, chemosensitivity and treatment outcomes of breast cancer. Breast Cancer (Auckl). 2009 Aug 17;3:47-60. PubMed PMID: 21556249
  39. Mandal SM, Dey S, Mandal M, Sarkar S, Maria-Neto S, Franco OL. Identification and structural insights of three novel antimicrobial peptides isolated from green coconut water. Peptides. 2009 Apr;30(4):633-7. PubMed PMID: 19111587.
  40. Ghosh K, Chandra K, Ojha AK, Sarkar S, Islam SS. Structural identification and cytotoxic activity of a polysaccharide from the fruits of Lagenaria siceraria (Lau). Carbohydr Res. 2009 Mar 31;344(5):693-8. PubMed PMID: 19264294.
 
Patents

Use of a truncated CCN1 promoter for cancer diagnostics, therapeutics and theranostics. (US9750823B2). Paul B. Fisher, Siddik Sarkar, Swadesh K. Das, Rupesh Dash, Devanand Sarkar, Windle. Assignee Virginia Commonwealth University. Patent granted on 2017-09-05.

 

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