Inflammation and Cancer


The Inflammation and Cancer Program expands inter-disciplinary collaborations in the topical area of GI and liver cancer models. The Program provides opportunities to translate basic observations into clinically-relevant observations. To accomplish this goal, the following services and expertise are provided:

  1. Access to GI and liver cancer animal models. An example is the azoxymethane/dextran sodium sulfate (AOM/DSS) colitis model of colorectal cancer. This model rapidly recapitulates the aberrant crypt foci-adenoma-carcinoma sequence that occurs in human CRC. Because of its high reproducibility and potency, the AOM/DSS model has become an outstanding model for studying colon carcinogenesis and a powerful platform for chemopreventive intervention studies.
  2. Assistance and expertise in the isolation and culturing of human and mouse primary stem cells from liver and tissues along the length of the GI tract (esophagus, stomach small/large intestine).
  3. A standardized protocol for the implantation and imaging of tumors.
  4. Standard operating procedures (SOPs), training models of cancer and techniques for isolating and culturing stem cells.

Inflammation and Cancer Collaborations

  • GI/liver cancer models and drug testing
  • Liver and GI stem cell isolation culture
  • Tumor imaging
  • SOP’s and training

Directors

Peter Dempsey

Peter Dempsey, PhD

Dr. Peter Dempsey's program focuses on the role of ADAM metalloproteinases in regulating extracellular signaling events involved in normal tissue homeostasis of the gastrointestinal tract and during injury/inflammation and cancer pathogenesis. He obtained his PhD in tumor cell biology at the Ludwig Institute for Cancer Research in Melbourne, Australia, under the supervision of Dr. Bob Whitehead, who is an expert in intestinal stem cell biology and the development of stem cell culture systems from different endodermally-derived tissues (gastric, intestine, colon, pancreas, liver, etc). His post-doctoral training at the Sloan Kettering Institute and Vanderbilt University was focused on understanding different aspects of growth factor signaling in the regulation of intestinal epithelial cell growth and differentiation. During his post-doctoral and junior faculty training with Dr. Bob Coffey at Vanderbilt University, he developed in vitro models to study the polarized trafficking and processing of ErbB ligands within different epithelial cell types. These studies provided novel insights into the regulation of autocrine ErbB receptor signaling and how the presentation, shedding and consumption of ErbB ligands can impact cellular responses. Upon establishing his own laboratory, a major focus has been on ADAM10 and ADAM17 biology and studying the biological significance of downstream signaling events regulated by ADAMs in vivo. At the University of Michigan, he developed a number of new transgenic gain-of-function and loss-of-function mouse models and enteroid stem cell culture systems to study the ADAM-mediated signaling events within the gastrointestinal tract and the pancreas, as well as projects to develop specific ADAM10 inhibitors for in vivo use. In late 2013, he moved to the University of Colorado AMC campus. His recent work in the intestine has focused on ADAM-mediated signaling events in regulation of stem cell function, injury/repair and in colitis-associated cancer models. The ADAM17 studies are focused on understanding, at a cellular level, how ADAM17 regulates communication between TNFa and Egfr/ErbB signaling pathways during intestinal stress/inflammation and within iPSC-derived human intestinal organoids (HIOs) obtained from a patient harboring autosomal recessive ADAM17 null mutation. The ADAM10 studies are focused on the role of ADAM10-mediated Notch signaling in regulating intestinal stem cell homeostasis and how ADAM10 signaling is modulated during mucosal injury/repair and in tumor initiation and progression. A current studies are examining how ADAM10 signaling modulates secretory progenitors such as Paneth cell progenitors to undergo stem cell reversion upon mucosal injury/repair. These studies use genetic mouse models and intestinal stem cell enteroid cultures to study signaling pathways that maintain the stem cell niche and control cell fate programming. In addition, the Dempsey lab has an extensive experience in the generation and analysis of both normal human enteroids and tumor organoids derived from patients with colorectal and pancreatic cancer.

Messersmith

Wells Messersmith, MD

Dr. Wells Messersmith is focused on clinical and translational cancer research and is the director of the Gastrointestinal (GI) Medical Oncology Program. This comprehensive program includes multi-disciplinary GI cancer clinics, tumor boards, and research endeavors. Dr. Messersmith’s laboratory is funded by the National Cancer Institute (NCI, R01) and he serves as the principal investigator on numerous national and local therapeutic trials. He is an active investigator in the developmental therapeutics laboratory, working on novel targeted therapies as well as correlative studies for use on human tissue samples. Dr. Messersmith is a member of multiple national committees, including NCI GI Steering Committee, NCI Colon Cancer Task Force, National Comprehensive Cancer Network (NCCN) Committee on Colon/Rectal/Anal Cancers (which sets treatment guidelines used internationally), NCCN Investigator Steering Committee, Medical Oncology Committee of the American Board of Internal Medicine (ABIM), and others.‚Äč