Michael B. Dwinell, PhD
Microbiology and Molecular Genetics
Medical College of Wisconsin
Director, Bobbie Nick Voss Laboratory
Research Focus: Mucosal Immunity; Immune Regulation in Cancer
PhD: University of Wisconsin, Madison (1996)
Postdoctoral Training: University of California, San Diego
Research in the Dwinell laboratory is broadly focused on inflammation and cancer. Translational research in the laboratory utilizes an array of cellular, molecular and genetic approaches to understand the mechanisms whereby the body’s natural immune processes are disrupted in human diseases. Completion of these studies will continue strengthen our identification of new targets for therapeutic intervention to improve human health. These studies are relevant to improved diagnoses and treatments in the inflammatory bowel diseases and cancers of the gastrointestinal tract, breast and pancreas.
The cells of the intestinal epithelium constitute an essential component of the mucosal immune system forming a dynamic physical barrier to prevent or limit entry of potentially noxious stimuli (Model). This epithelial barrier is injured or damaged by pathogens or upon excessive stimulation with inflammatory mediators including cytokines, chemokines, and reactive oxygen metabolites (red arrow). Immune effector molecules, including chemokines and defensins within the surrounding tissue are critical for effective host defense. Work in the laboratory indicates several of those host defense mediators bind and activate receptors on epithelial cells to regulate homeostatic growth and differentiation or initiate repair processes needed for a healthy mucosal barrier (green arrow). In cancers of the colon, breast, lung and pancreas the epithelial maintenance and repair processes become dysregulated during neoplastic transformation leading to disorganization and progression to cancer (yellow arrow). Cells in the carcinoma tissue can become invasive and increasingly motile leading to their metastasis to distant tissues.
Research projects in my lab include:
Innate Immune Barrier Repair. These studies are investigating the impact of chemokines on maintenance and repair of the mucosal epithelium. Human model intestinal epithelia and transgenic murine models are being used to expand the paradigm that chemokines solely regulate leukocyte cell trafficking. Research from the laboratory show for the first time that a battery of chemokines can regulate mucosal wound healing, epithelial cell adhesion and migration processes necessary for innate immune defense.
Chemokines in Cancer. These studies are defining the role for chemokines in tumor metastasis and carcinogenesis. Cancer of the human colon, breast, and lung represent a failure in normal epithelial growth, differentiation, and migration. Human carcinoma cell lines as well as murine models of tumorigenesis and metastasis are being used to define the molecular events regulating transcription of chemokine genes and the functional impact of those molecules in tumor growth, adhesion, invasion and metastasis.
Innate Defense against Pathogens. These investigations are delineating innate immune responses of epithelial cells infected by microbial pathogens. Enteric pathogens utilize a number of different host colonization strategies, with interactions at the intestinal epithelium being the common pathogenic feature. Studies completed within the laboratory are defining the cellular and biochemical mechanisms epithelial cells utilize to limit disease following infection by food- or water-borne microbes.
Research in the Dwinell laboratory are supported through grants from the National Institutes of Health, the Crohn’s and Colitis Foundation of America and philanthropic donations from the community. Additional support comes from the Medical College of Wisconsin Digestive Disease Center, the Cancer Center (http://www.mcw.edu/cancercenter) and kind donations from the Bobbie Nick Voss Charitable Funds (http://www.bobbiesays.com).