Research

Overview

Dr. VanSaun's lab focuses on understanding the influence of adipose secreted cytokines (adipokines) on pancreatic cancer progression. The epidemic of obesity is a significant risk factor, associated with 40% of all cancers, including pancreatic cancer, which ranks as the third deadliest cancer with an approximate five-year survival rate of 9%. Obesity associated inflammation incites a yin/yang dysregulation of adipokines, whereby pro-tumorigenic adipokine (leptin, IL-6 and IL-1β) levels increase and anti-tumorigenic adipokine (adiponectin) levels decrease. This dysregulation results in enhanced activation of mitogenic pathways, such as KRAS, that drive cancer progression and promote the recruitment of innate inflammatory cells. We have spent the past eight years studying adipocyte-tumor crosstalk and understanding how secreted factors from the adipose tissue (adipokines) ultimately affect the tumor microenvironment. We have developed mouse and human in vitro PDAC-adipocyte co-culture models as well as in vivo genetically engineered mouse models of pancreatic cancer combined with high fat diet induced obesity to understand the impact of obesity on pancreatic cancer progression. We currently have multiple projects ongoing in the laboratory to understand: 1) role of adipose-tumor crosstalk in pancreatic cancer progression, 2) role of tyrosine phosphatases in regulation of MAPK signaling, 3) regulation of immune function in the tumor microenvironment, 4) metabolic alterations in response to phosphatase activity, 5) the potential use of adiponectin agonists as anti-cancer therapeutics.

• R01 - Counteracting molecular mechanisms of obesity dependent PDAC progression, NIH/NCI, PI

• VanSaun, M., N, Lee, I., K, Washington, M., K, Matrisian, L, Gorden, D., L. 2009. High fat diet induced hepatic steatosis establishes a permissive microenvironment for colorectal metastases and promotes primary dysplasia in a murine model.. The American journal of pathology, 175 (1), 355-64
• Vansaun, Michael., N. 2013. Molecular pathways: adiponectin and leptin signaling in cancer.. Clinical cancer research : an official journal of the American Association for Cancer Research, 19 (8), 1926-32
• Messaggio, F, Mendonsa, A., M, Castellanos, J, Nagathihalli, N., S, Gorden, L, Merchant, N., B, VanSaun, M., N. 2017. Adiponectin receptor agonists inhibit leptin induced pSTAT3 and in vivo pancreatic tumor growth.. Oncotarget, 8 (49), 85378-85391
• Manley, Sharon., J, Olou, Appolinaire, Messggio, Fanuel, Jack, Ambrose, Joseph, VanSaun, Michael., N. 2022. Synthetic adiponectin receptor agonist, AdipoRon, induces glycolytic dependence in pancreatic cancer cells. Cell Death and Disease.
• Olou, Appolinaire, Jack, Jarrid, Ambrose, Joseph, Walsh, McKinnon, Eades, Austin, VanSaun, Michael., N. 2022. SHP2 regulates adipose maintenance and adipocyte-pancreatic cancer cell crosstalk via PDHA1. Journal of Cell Communication and Signaling