Sushil Kumar

Assistant Professor, Biochemistry and Molecular Biology

KumarPhone: 402-559-3138 (Office)
    Location: DRC1 7010
Fax: 402-559-6650

Ph.D., CCSHAU, 2001


My overall research interest is to understand the role of tumor microenvironment (TME) in the progression of pancreatic cancer (PC) and regulation of oncogenic molecules, especially mucins. PC is characterized by highly complex microenvironment, where stromal cells often outnumber cancer cells. One of the hallmarks of PC is aberrant overexpression of various members of the mucin (MUC) family of proteins including MUC1, MUC 4 and MUC16 that are detectable in earliest precursor lesions (i.e., pancreatic intraepithelial neoplasia [PanIN]) and progressively increase with disease advancement. While working on MUC regulation during PC progression, we identified nuclear receptor co-activator-3 (NCOA3) as an important modulator of MUC1 and MUC4 expression and suggested its critical role in pancreatic cancer progression. In addition to mucin regulation, NCOA3 regulates the expression of LOXL-2, cytokines, and other essential molecules that support PC microenvironment. LOXL-2 is the most significantly down-regulated gene after NCOA3 silencing, which has previously been shown to be critical for the hardening of desmoplasia by crosslinking extracellular matrix proteins (ECM) in PC. We plan to target NCOA3 that will simultaneously downregulate MUC expression, inflammation, and stiffness in the tumor microenvironment, therefore, counter the barrier imposed by tumor stroma (desmoplasia) for improved delivery of chemotherapy and reduce the metastatic burden (manuscript under revision). Also, we are developing innovative technologies to delineate the crosstalk between various cellular components in the TME mediated through cytokines. On these lines, we have established a defined in vitro 3D co-culture system to investigate the cytokine contribution of various cell types to TME and delineate the crosstalk mediated through cytokines, the role of ECM in cell migration and invasion, and immune cell recruitment.

Research Interest

Tumor Microenvironment

 Selected Publications

  1. Kumar S*, Cruz E, Joshi S, Patel A, Jahan R, Batra SK, Jain M. Genetic Variants of Mucins: Unexplored Conundrum. Carcinogenesis. PubMed PMID: 27838635 DOI: 10.1093/carcin/bgw120. *corresponding author

  2. Wang Y, Kumar S*,Rachagani S,Sajja BR, Xie Y, Hang Y, Jain M, Li J, Boska MD, Batra SK,Oupický D. Polyplex-mediated inhibition of chemokine receptor CXCR4 and chromatin-remodeling enzyme NCOA3 impedes pancreatic cancer progression and metastasis. Biomaterials. 2016; 101: 108-20. PubMed PMID: 27267632; PubMed Central PMCID: PMC4921319 *equal contribution

  3. Kumar S and Batra SK. Interleukin-22 connects smoking and pancreatic fibrosis during chronic pancreatitis. Gastroenterology. 2016 151(6):1067-70. PubMed PMID: 27983953 DOI: Editorial commentary for the manuscript entitled “Aryl Hydrocarbon Receptor Ligands in Cigarette Smoke Induce Production of Interleukin-22 to Promote Pancreatic Fibrosis in Models of Chronic Pancreatitis.”

  4. Joshi S, Kumar S*, Ponnusamy MP, Batra SK*. Hypoxia-induced oxidative stress promotes MUC4 degradation via autophagy enhanced pancreatic cancer cell survival. Oncogene. 2016 Nov 10;35 (45): 5882-92 PubMed PMID: 27109098; PubMed Central PMCID: PMC5079846. *corresponding author

  5. Joshi S, Cruz E, Rachagani S, Guha S, Brand RE, Ponnusamy MP, Kumar S*, and Batra SK*. Bile acid mediated overexpression of MUC4 via FAK-dependent c-Jun activation in pancreatic cancer. Mol Oncol. 2016; 10(7): 1063-77. PubMed PMID: 27185392; PubMed Central PMCID: PMC4972654. *corresponding author

  6. Kumar S, Das S, Rachagani S, Kaur S, Joshi S, Johansson SL, Ponnusamy MP, Jain M, and Batra SK. NCOA3-mediated upregulation of mucin expression via transcriptional and post-translational changes during the development of pancreatic cancer. Oncogene. 2015 Sept 10; 34 (37):4879-89. PubMed PMID: 25531332; PubMed Central PMCID: PMC4476953

  7. Kumar S, Torres MP, Kaur S, Rachagani S, Joshi S, Johansson SL, Momi N, Baine MJ, Gilling CE, Smith LM, Wyatt TA, Jain M, Joshi SS, and Batra SK. Smoking accelerates pancreatic cancer progression by promoting differentiation of MDSCs and inducing HB-EGF expression in macrophages. Oncogene. 2015 Apr 16; 34(16):2052-60. PubMed PMID: 24909166; PubMed Central PMCID: PMC4457293.

  8. Joshi S, Kumar S, Bafna S, Rachagani S, Wagner KU, Jain M, and Batra SK. Genetically engineered mucin mouse models for inflammation and cancer. Cancer Metastasis Rev. 2015 Dec 34(4):593-609; PubMed PMID: 25634251; PubMed Central PMCID: PMC4520780.

  9. Kaur S, Kumar S, Momi N, Sasson AR, and Batra SK. Mucins in pancreatic cancer and its microenvironment. Nat Rev Gastroenterol Hepatol. 2013 Oct 10(10):607-20. PubMed PMID: 23856888; PubMed Central PMCID: PMC3934431.

  10. Kassmeier MD, Mondal K, Palmer VL, Raval P, Kumar S, Perry GA, Anderson DK, Ciborowski P, Jackson S, Xiong Y, and Swanson PC. VprBP binds full-length RAG1 and is required for B-cell development and V (D) J recombination fidelity. EMBO J. 2012 Feb 15;31(4):945-58. PubMed PMID: 22157821; PubMed Central PMCID: PMC3280554.

  11. Rachagani S, Torres MP, Kumar S, Haridas D, Baine M, Macha MA, Kaur S, Ponnusamy MP, Dey P, Seshacharyulu P, Johansson SL, Jain M, Wagner KU, Batra SK. 2012. Mucin (Muc) expression during pancreatic cancer progression in spontaneous mouse model: potential implications for diagnosis and therapy. J Hematol Oncol., 26 (5):68-72. PubMed PMID: 23102107; PubMed Central PMCID: PMC3511181.

  12. Tarang S, Kumar S, Batra SK. Mucins and toll-like receptors: kith and kin in infection and cancer. Cancer Lett. 2012 Aug 28; 321(2):110-9. PubMed PMID: 22306702; PubMed Central PMCID: PMC3285398.

  13. Kumar S, Swanson PC. Full-length RAG1 promotes contact with coding and intersignal sequences in RAG protein complexes bound to recombination signals paired in cis. Nucleic Acids Res. 2009 Apr;37(7):2211-26. PubMed PMID: 19233873; PubMed Central PMCID: PMC2673416.

  14. Shlyakhtenko LS, Gilmore J, Kriatchko AN, Kumar S, Swanson PC, Lyubchenko YL. Molecular mechanism underlying RAG1/RAG2 synaptic complex formation. J Biol Chem. 2009 Jul 31; 284(31):20956-65. PubMed PMID: 19502597; PubMed Central PMCID: PMC2742861.

  15. Swanson PC, Kumar S and Raval P. 2009. Early Steps of V (D) J Rearrangement: Insights from biochemical studies of RAG: RSS complexes. In Advances in Experimental Medicine and Biology. Ed. Pierre Ferrier, Landes Bioscience, and Springer Science + Business Media: 650, p1-15.

  16. Raval P, Kriatchko AN, Kumar S, Swanson PC. Evidence for Ku70/Ku80 association with full-length RAG1. Nucleic Acids Res. 2008 Apr;36(6):2060-72. PubMed PMID: 18281312; PubMed Central PMCID: PMC2330247.