The MU College of Veterinary Medicine recently completed its fourth annual Veterinary Research Scholars Program (VRSP). Sponsored by Merck, Merial, Pfizer and the MU CVM, the VRSP gives students in the Pre-Veterinary Medical Scholars Program and first- and second-year veterinary students the opportunity to spend their summer break exploring research. As outlined in … [Read more...]
We are focused on the discovery of the mutations responsible for heritable canine diseases. Over the years we have identified approximately 40 such mutations. Currently our main strategy is to generate and analyze whole genome sequences from affected dogs, identify suspicious DNA variations, and do PCR-based DNA tests to see which candidate variations occur in affected dogs but not normal dogs. A Veterinary Research Scholar would be taught to do the PCR-based DNA tests and asked to test normal and affected dogs to determine the cause of an inherited canine disease. Before the beginning of 2018, we expect to receive 21 new whole genome sequences each generated with DNA from a dogs with a different inherited disease such as Elhers-Danlos syndrome, lysosomal storage disease, epilepsy, megaesophagous, cataracts, ataxia, and alopecia. By March we 2018, we expect whole genome sequence data for several more dogs with interesting diseases.
The focus of my research is to understand the mechanisms that regulate the development and progression of heart failure. In particular, my research investigates the immunomodulatory role of adrenergic receptors and following cardiac injury and as a potential therapeutic target for the treatment of heart disease. β-adrenergic receptors (βAR) are critical regulators of cardiac function both in the healthy and diseased heart. Cardiac βAR are differentially expressed with the β1AR subtype being predominantly localized to cardiomyocytes where they are known to regulate contractility. β2AR are predominate on other cells types including fibroblasts and immune cells. During heart failure, βAR signaling becomes altered and subtype expression ratios change, leading to detrimental hypertrophy, increased cardiomyocyte apoptosis, fibrosis and cardiac dysfunction. As a result of this dysregulation in βAR signaling, they are a common therapeutic target for the treatment of heart diseases including myocardial infarction (MI) and heart failure.
Following MI, there is an intense inflammatory response that is critical to for clearing the area of dying cardiomyocytes and extracellular matrix debris and activating remodeling pathways. It has been known for over 100 years that the sympathetic nervous system can influence immune responses in part through its activation of βAR. βAR are expressed on virtually all cells of the immune system where they impact cell function in a cell type, activation state and disease dependent manner. β2AR are the most highly and widely expressed βAR subtype in the immune system where they are known to influence a number of different functions including hematopoiesis, lymphopoiesis, thymopoiesis, lymphocyte homing, immune cell maturation and immune cell function. Regulation of immune functions by β2AR is thought to contribute to a number of different diseases including autoimmune diseases and wound healing. However, the manner in which β2AR regulate immune responses is often disease dependent and how β2AR regulation of immune responses influences the pathogenesis and progression of heart failure is completely unknown. We have identified an important role for β2AR in suppressing early immune responses, which leads to impairments in the hearts ability to remodel following ischemic injury. Mice that lack β2AR in their immune system have decrease leukocyte infiltration following MI as a result of decreased migratory ability through alterations in the chemokine receptor CCR2. There are also impairments in egress of immune cells from the spleen. Ongoing studies are investigating the role of β2AR in regulating specific immune cell populations that impact healing following MI, identifying novel mechanisms through which β2AR are influencing the immune response, the impact of β-blockers on inflammatory responses and novel therapeutic strategies targeting β2AR in the immune system to improve outcome after MI.
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My lab is focused on a broad-based highly innovative, translational research program in molecular basis of eye diseases. My major research interest is to identify the early key initiating oxidative, inflammatory factors/signaling molecules and immune cells, which render metabolic derangements and eventually damage both neuronal and vascular cells in the pathophysiology of the eye diseases. Current projects in the lab involve wound healing mechanisms and nanodelivery, protein aggregation diseases, anti-angiogenic drugs, stem cell therapeutics and molecular mechanisms involving diabetic retinopathy and age-related retinal degeneration to decipher new drug targets for these blinding diseases.