Sushil Kumar

Assistant Professor, Biochemistry and Molecular Biology

Kumar

Phone: 402-559-7754 (Office)
Fax: 402-559-6650
Email

Education/Training:
Ph.D., CCSHAU, 2001

Research

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. 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 (in press)
  2. Joshi S, Cruz E, Rachagani S, Guha S, Brand RE, Ponnusamy MP, Kumar S# and Batra SK. 2015. Bile acid mediated overexpression of MUC4 via FAK-dependent c-Jun activation in pancreatic cancer. Mol Oncol. doi: 10.1016/j.molonc.2016.04.007.
  3. Joshi S, Kumar S#, Ponnusamy MP and Batra SK. 2016. Hypoxia-induced oxidative stress promotes MUC4 degradation via autophagy to enhance pancreatic cancer cell survival. Oncogene. doi:10.1038/onc.2016.119  
  4. Kumar S, Das S, Rachagani S, Kaur S, Joshi S, Johansson SL, Jain M and Batra SK. 2015. NCOA3 regulate mucin expression via transcriptional and post-translational regulation during the development of pancreatic cancer. Oncogene, 10; 34(37): 4879-89.
  5. 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 Surinder K. Batra. 2014. Smoking accelerates pancreatic cancer progression by promoting differentiation of MDSCs and inducing HB-EGF expression in macrophages. Oncogene, 16; 34(16): 2052-60.
  6.  Joshi S, Kumar S, Bafna S, Rachagani S, Wagner KU, Jain M, and Batra SK. 2015. Genetically engineered mucin mouse models for inflammation and cancer. Cancer Metastasis Rev., 34(4): 593-609.
    1. Kaur S, Kumar S, Momi N, Sasson AR, Batra SK. 2013. Mucins in pancreatic cancer and its microenvironment. Nat Rev Gastroenterol Hepatol. 10 (10): 607-20.
    2. 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.
    3. Kassmeier MD, Mondal K, Palmer VL, Raval P, Kumar S, Perry GA, Anderson DK, Ciborowski P, Jackson S, Xiong Y, Swanson PC. 2011. VprBP binds full-length RAG1 and is required for B-cell development and V (D) J recombination fidelity. EMBO J., 13; 31 (4):945-58.
    4. Kumar S and Swanson PC. 2009. Full-length RAG1 promotes contact with coding and intersignal sequences in RAG protein complexes bound to recombination signals paired in cis. Nucleic Acids Res., 37: 2211 – 2226.
    5. 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.
    6. Shlyakhtenko LS, Gilmore J, Kriatchko AN, Kumar S, Swanson PC, and. Lyubchenko YL. 2009. Molecular Mechanism Underlying RAG1/RAG2 Synaptic Complex Formation. J. Biol. Chem., 284: 20956-20965.
    7. Raval P, Kriatchko AN, Kumar S, and Swanson PC. 2008. Evidence for Ku70/Ku80 association with full-length RAG1. Nucleic Acid Res., 36:2060-2072
    8. Kumar S, Sharma NM, Saharan MR and Singh R. 2005. Extracellular acid protease from Rhizopus oryzae: Purification and Characterization. Process Biochemistry, 40: 1701-1705.
    9. Kumar S, Sharma NM, Saharan MR and Singh R. 2004. Biochemical changes during ripening of cheddar cheese prepared by milk clotting enzyme from Rhizopus oryzae. J Food Sci. Technol., 41(3): 279-283.
    10. Sharma NM, Sushil Sharma and Sawhney SK. 2003. A novel method for the immobilization of tyrosinase to enhance stabilityBiotechnol Appl Biochem., 38(2): 137-141. PMID: 12760744
    11. Kumar S, Sharma NM, and Raina R. 2002. Influence of repeated oral administration of triazophos on intestinal absorption of nutrients in rats. Indian J. Vet. Pharmacol. 1: 71-76.

*Equal contribution

#Co-corresponding author