Aging Panel Description: Age is not a disease, or is it? The effect of aging on human and canine performance. Aging is a molecular process of change that affects cells at the level of DNA, we see the manifestations through the physical and behavioral changes with advancing age. Some of the most common age related conditions affect the dog’s musculoskeletal and neurologic systems.
- Manti Guha, PhD
- Michael Mison, DVM, BS, DACVS
- Charles Vite, DVM, PhD, ACVIM
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Manti Guha, Phd:
The overarching goal of my research is to understand the mechanisms by which mitochondrial genome defects and mitochondrial dysfunction contribute to cancer and aging.
One of my research areas is focused on exploring the contribution of mitochondrial dysfunction towards tumor metastasis. I have shown that a metabolic switch to glycolysis involving IGF1-receptor/ AKT is the key to adaptation in cells with reduced mtDNA content and mitochondrial stress. I have identified that in response to mitochondrial stress, nuclear oncogenes are transcriptionally upregulated via activation of a novel transcriptional coactivator hnRNPA2. I have demonstrated that mitochondrial stress signaling induces cellular plasticity and reprograms towards metastasis.
Another focus of my research is investigating the relevance of mitochondrial dysfunction induced telomere defects. Chromosomal aberrations and activation of the DNA damage response observed in tumor cells has been attributed to telomere shortening. Additionally, telomere shortening is a critical event during cellular aging and contributes to aging associated pathologies. However, the underlying molecular mechanisms remain unclear. My recent studies suggest that mitochondrial stress mediated signaling plays a causal role in telomere shortening, via epigenetic mechanisms, while also reactivating telomerase, a mechanism by which cancer cells escape senescence. I am interested in mechanistically understanding why, in response to mitochondrial dysfunction, some cells undergo telomere shortening leading to cellular aging while others undergo tumorigenic transformation.
Michael Mison, DVM, PhD, DACVS:
Dr. Michael Mison DVM, DACVS joined the Penn Vet surgery and oncology departments in the summer of 2015. Dr. Mison brings to Penn Vet particular interest and experience in oncological and soft tissue surgery and will spend the majority of his clinical time with the Comprehensive Cancer Care team. Dr. Mison received his veterinary degree (with high honors) from the University of Florida in 1998 and completed a rotating internship and surgical residency at Michigan State University. Dr. Mison brings with him an extensive resume of teaching experience and awards including the prestigious Carl Norden Distinguished Teaching Award which he received as a 2nd-year Assistant Professor at Washington State University College of Veterinary Medicine. He also held a position as Affiliate Assistant Professor in the Department of Comparative Medicine at the University of Washington School of Medicine. Dr. Mison subsequently left Washington State University for private specialty practice, and in 2007 founded Seattle Veterinary Specialists as a managing partner. He maintained his enthusiasm for teaching by serving as a locum tenens surgeon/instructor at several other veterinary schools during his time in private practice.
Charles Vite, DVM, PhD, ACVIM
Dr. Charles H Vite is an Associate Professor of Veterinary Neurology at the School of Veterinary Medicine. Dr. Vite trained as a DVM at Purdue University and trained in Veterinary Neurology and received his PhD in Cell and Molecular Biology from the University of Pennsylvania. His focus is to improve the characterization and treatment of neurodegenerative diseases by studying naturally-occurring feline and canine models of human diseases including globoid cell leukodystrophy. He is incoming Principal Investigator (PI) of a P40 grant that maintains breeding colonies of large animal models of human genetic disease.
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