Sushil Kumar

Assistant Professor, Biochemistry and Molecular Biology

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

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

Research

My laboratory is working on the pancreatic pathologies including pancreatic cancer and pancreatitis using multiple murine models, organoid, and 3D cell culture-based technologies. PC is a highly lethal malignancy with a five-year survival rate of ~9 % and is expected to become the second leading cause of cancer-related mortality by 2030. We are investigating the role of various intrinsic factors and microenvironment in the progression and metastasis of pancreatic cancer and the regulation of expression of oncogenic molecules. Among intrinsic factors, we are focusing on the role of nuclear receptor coactivator-3 (NCOA3) and CXCR3 in the initiation, progression, and metastasis of pancreatic cancer. Our studies have demonstrated that NCOA3 regulates the expression of various chemokines, LOXL-2, FUT8, IGFBP3, MMP7, and other essential molecules that support PC progression. We have recently identified a novel interaction between NCOA3 and YAP1. Using inflammation-mediated models, YAP1 has been demonstrated to play a critical role in acinar-to-ductal metaplasia (ADM), an essential step during PC initiation, progression, and aggressiveness. The interaction between NCOA3 and YAP1 and downregulation of YAP1 signature genes following NCOA3 silencing in PC cells suggest an important role of NCOA3 in PC initiation and progression. We are presently investigating the contribution of NCOA3 in ADM and pancreatic cancer progression using a conditional murine model of NCOA3. 

Similarly, we have demonstrated that CXCR3, a G-protein coupled receptor (GPCR) plays a critical role in protecting the cancer cells during the hematological dissemination by promoting the crosstalk between cancer cells and platelets. Platelets are the predominant source of CXCR3 ligand, PF4 in the body and pharmacological inhibition (AMG487) of CXCR3 significantly reduce the metastatic burden in pancreatic cancer, suggesting the important role of CXCR3/PF4 axis in the metastatic process. We are presently working to elucidate the molecular mechanism of CXCR3-facilitated metastasis of pancreatic cancer cells.

As inflammation is critical for the progression of cancer. We have identified a unique signature of cytokines and other inflammatory mediators including NGAL in pancreatic cancer and pancreatitis (benign inflammation of the pancreas), through global gene profiling using autochthonous murine models. Exploring on these lines, we are presently investigating the mechanistic contribution of CXCR2-ligands and NGAL in the severity of pancreatitis. Our studies have revealed that deficiency of Ngal/LCN2 in the experimental murine model of acute pancreatitis; significantly reduce the severity of the disease plausibly through reduced expression of MMP9 in the pancreas of Ngal/LCN2 KO animals during acute pancreatitis. Further, there is marked a reduction in the infiltration of neutrophils, macrophages, and lymphocytes in the pancreas of Ngal/LCN2 KO animals. Concurrently, we have investigated the role of environmental factor in pancreatic cancer and pancreatitis. Our study has demonstrated that alcohol abuse and smoke exposure activate the pancreatic stellate cells, accelerate the progression of pancreatic cancer, and increase the severity of pancreatitis. Now we are extending these observations and investigating the role of smoke exposure on the severity of the acute and chronic pancreatitis.

Research Interest
Tumor Microenvironment

Publications:
My Publications