Moorthy Ponnusamy

Assistant Professor, Biochemistry and Molecular Biology

Moorthy.jpgPhone: 402-559-1170
Fax: 402-559-6650
Email

Education/Training:
Ph.D., Madras University, INDIA, 2005

Research:

Research Interest: Characterization of cancer stem cells, Mechanism of Metastasis and Tumor Glycobiology

Mechanism of cancer stem cell maintenance: My primary goal is to identify and characterize the cancer stem cell populations in different cancers. Over the last several years, it has been identified that a small population (less than 5%) of cancer cells, referred as “Cancer Stem Cells (CSCs)” or “side population cells (SP)”, is responsible for the aggressiveness, metastasis and resistance of ovarian cancer cells to therapy. Based on our previous study on role of human polymerase association factor 1/pancreatic differentiation 2 (hPaf1/PD2) in the maintenance of self-renewal in mouse embryonic stem cells, I hypothesize that hPaf1/PD2 may play a role in regulating self-renewal of CSCs. This project seeks to investigate the role and mechanism of a novel molecule hPaf1/PD2 in cancer stem cells. The identification of cancer stem cell specific marker hPaf1/PD2 and its role in CSC maintenance would provide extremely important information that is critical in advancing towards the long-term goal of developing novel therapeutic strategies for cancer stem cell population.

Ductal lineage-differentiation of cancer stem cells in the progression of pancreatic cancer: Previous studies for pancreatic cancer progression suggest the potential involvement of acinar cells and postulated stem cells in the development of pancreatic cancer. This progression occurs via “acinar-to-ductal metaplasia” (ADM) process. Based on this background, we focused to investigate the role of PAF1/PD2 in acinar-to-ductal-metaplasia.

Smoking-induced enrichment of pancreatic cancer stem cells: Cigarette smoking is one of the leading risk factors for pancreatic cancer. Major focus of this proposal is to investigate the role of smoking on the enrichment of pancreatic cancer stem cells (PCSCs) by characterizing the activating stem cell signatures induced by cigarette smoke and its downstream impact on the aggressiveness for pancreatic cancer. The proposed studies will expand the current understanding of the impact of continued smoking on pancreatic cancer progression and define the underlying cellular and molecular mechanisms involved in the transformation, activation and expansion of CSCs. Therefore, we focused on investigating the smoking mediated enrichment of pancreatic cancer stem cells, based on our previous observations (Oncogene, 2013, Gastroenterology, 2014). We have recently identified a novel mechanism for smoking mediated enrichment of pancreatic cancer stem cells (Gastroenterology, 2018).

 Schematic diagrams represent the differentiation, dedifferentiation and therapeutic implication of cancer stem cells

Organoid 3D-culture model to analyze cancer stem cells and therapeutics: Recent evidence demonstrates that 3D-organoid culture has emerged in the forefront of experimental biology. Depending on the source tissue, growth factors, and inhibitors provided, organoids can be programmed to recapitulate the biology of a system and progression of pathology. Organoids are genetically stable, and genetically amenable, making them very suitable tools to study tissue homeostasis and cancer. Therefore, our primary goal is to establish an organoid culture to understand therapy response since it mimics tumor biology and physiology better than monolayer culture and provides a scope for personalized treatment. We have developed organoids from the normal mouse pancreas as well as the pancreatic tumor from Kras;p53;PdxCre mice model. We have also developed human pancreatic tumor organoids.

Published Manuscripts 

Full list of my publications.

Current Funding:

National Institutes of Health, R01CA210637 (PI-Ponnusamy MP)
Title: Role of PD2/Paf1 in Pancreatic Acinar to Ductal Metaplasia
Objective: The goal of this grant application is to investigate the multi-functional role of pancreatic differentiation 2 (PD2) in acinar-to-ductal-metaplasia (ADM) and ductal lineage-differentiation of pancreatic cancer stem cells (CSC) during the progression of pancreatic ductal adenocarcinoma (PDAC).
Role: Principal Investigator
 
National Institutes of Health, P01CA217798 (PI-Batra SK)
Title: Pancreatic Cancer and Metastasis
Objective: Overall theme of the P01 program proposal is to understand the mucin 16 (MUC16)–mediated molecular mechanisms of pancreatic cancer metastasis.
Role: Co-Investigator
 
National Institutes of Health, R01CA183459 (PI-Batra SK) 
Title: Targeting Mucin and EGFR Axis in Pancreatic Cancer
Objective: The overall aim of the proposed study is to test and develop a novel combination therapy against lethal pancreatic cancer by combining the afatinib and cytotoxic agent gemcitabine.
Role: Co- Investigator

Awards:

  1. Received Joseph P. Gilmore Distinguished New Investigator Award-2018
  2. Received Distinguished New Investigator Award-2018