Michael VanSaun, PhD

The overall goal of my research is to identify novel therapeutics to prevent and/or reduce the mortality from cancer. I have a broad background in cellular biology, with specific training and expertise in cancer biology and cell signaling. I have studied cancer for 15 years, of which I have spent the past 10 years specifically focused on liver and pancreatic cancer; now expanding into bladder cancer. My experience and qualifications in this field of study are exemplified by some of my recent peer reviewed publications, awarded grants, and through participation in meetings and associations with the Pancreatic Cancer Action Network, the American association for cancer research, the American Pancreatic Association and the American Gastroenterological Association.
The primary concept of our studies is to determine how cells communicate with one another to regulate cancer progression. Additionally, we are interested in how obesity impacts the development and progression of cancer. We are interested in factors released from adipose tissue that ultimately regulate mitogenic activity within cancer cells. Our studies incorporate genetically engineered mouse models of cancer; focusing of the KPC (Kras^G12D; LSL-p53^R172H; Ptf1a^Cre) mice, orthotopic implantations, as well as advanced in vitro co-culture model systems.

Dr. VanSaun's lab is actively investigating 5 different projects:

1. To understand the role of mitochondrial SHP2 on pancreatic cancer progression. We have identified that suppression of SHP2 causes mitochondrial dysfunction and loss of respiration. We are performing phospho-proteomic analysis to understand the mitochondrial targets of SHP2 in order to understand how SHP2 regulates metabolism.

2. To define the role of the smooth muscle during invasive bladder cancer progression. We have demonstrated that MIBC induces an injury response in bladder smooth muscle cells. We believe induction of this injury response is a way for the cancer to trick the muscle into destabilization of cellular adhesions, making a hole in the muscle through which the cancers can escape and metastasize.

3. To determine whether induction of thermogenesis can regulate pancreatic cancer progression. We known that obese adipose secretes mitogenic and inflammatory factors that increase growth of pancreatic cancers. We are hoping to activate thermogenesis in adipocytes as a novel approach to suppressing the negative effects of obese adipose.

4. To understand how loss of TGFbR2 increases pancreatic cancer progression. Loss of TGFbR2 in the KrasG12D mouse model of pancreatic cancer significantly increases the incidence of cancer and decreases the ​overall ​lifespan. We ​performed RNAseq analysis of ​cell lines from our mouse models ​to elucidate ​novel pathways driving this phenomenon. We are currently testing these pathways to find novel targets that could help patients with these specific ​genetic ​mutations or loss of function.

5. To understand the role of neuroendocrine cells in pancreatic cancer progression. We have discovered that CLEC4F labels a unique set of neuroendocrine cells in pancreatic ​cancers. We have generated truncation mutants to understand the ​functional role for this protein in pancreatic cancer.

Adiponectin receptor agonists inhibit leptin induced pSTAT3 and in vivo pancreatic tumor growth.

High fat diet induced hepatic steatosis establishes a permissive microenvironment for colorectal metastases and promotes primary dysplasia in a murine model.

Modulation of the leptin receptor mediates tumor growth and migration of pancreatic cancer cells.

Molecular pathways: adiponectin and leptin signaling in cancer.

SHP2 regulates adipose maintenance and adipocyte-pancreatic cancer cell crosstalk via PDHA1

Synthetic adiponectin receptor agonist, AdipoRon, induces glycolytic dependence in pancreatic cancer cells

R01CA231052-01A1 - Counteracting molecular mechanisms of obesity dependent PDAC progression

R03CA286703 - Enhancing intratumoral T cell infiltration to improve checkpoint blockade efficacy via Plectin-AAV targeted siCXCL5 in PDAC