Department of Biological Sciences
|Title:||Associate Professor, Director of the Cardiovascular Technology Program
Research Concentration - Stem Cells & Developmental Biology; Biology of Cellular Stress
College of Arts and Sciences
|Office:||CLS, Room 703|
Much like we seek to maintain balance in our personal lives, so too are biological systems geared to maintain homeostasis. Failure to adapt to environmental stressors that alter this homeostatic balance can result in disease. Our research group is interested in understanding how two very similar ubiquitin ligases, ITCH and WWP1, independently function to maintain the normal proteome in human health. Ubiquitin ligases are one of a series of enzymes that post-translationally modify a target protein to influence its longevity, function, and/or subcellular localization. Using mouse models, we explore the molecular, cellular, and physiologic phenotypes of both gain- and loss-of-function of the ITCH and WWP1 proteins. Our work has shown that animals lacking ITCH develop a progressive and systemic inflammatory disorder that is particularly evident at mucosal surfaces like the skin, lungs, and gastrointestinal tract. We would like to understand how ITCH normally functions in innate immune cells and in the surface epithelium of the intestines to properly maintain a barrier between the organism and associated microbiota to prevent presentation of pathologies like inflammatory bowel disease and to determine if some of these changes might arise due to altered developmental programs.
Despite the fact that WWP1 and ITCH share >71% similarity, are both ubiquitously expressed from early on in development, and have been described to target many of the same proteins for ubiquitination, animals lacking WWP1 do not have an obvious deleterious phenotype. Rather, it has been shown that overexpression of WWP1 is related to age-associated pathologies like cancer, osteoporosis, and cardiac dysfunction (both electrical and mechanical). Our work aims to explore the way WWP1 influences the structure and function of cardiomyocytes and cardiac fibroblasts as well as the dynamics of the extracellular matrix in the heart to influence normal cardiac function. Additionally, our ongoing research is directed towards understanding whether these precocious cellular and physiological cardiac aging phenotypes might be the consequence of perturbed cardiac developmental dynamics regulated by WWP1.