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Aging, Metabolism and Mitochondria


Research in the Department of Animal Biology on aging and metabolism encompasses broad aspects of chemical, biological and oxidative stress as well as neuronal stress.  Our labs have Jacenko-bone_nicheproduced groundbreaking discoveries in the study of spermatogonial stem cells and its niche, transgenerational germ cell reprogramming and the role of transcription factor NF-kB in chronic inflammatory diseases.

These studies employ diverse cutting edge approaches including genetic models of human disease, metabolic profiling, microRNA analysis, metabolic activation of environmental toxins, and elucidation of an array of signaling pathways.

Research from our labs contributes to efforts to better understand and develop treatments for age related diseases including osteoporosis and related muscloskeletal disorders, cancer, reproductive diseases, and maternal stress on development.


Faculty


  • Dr. Narayan Avadhani
    • Our lab is focused on mitochondrial genetics and the role of mitochondrial dysfunctions in several pathological processes.  Diseases and pathologies as diverse as myocardial ischemia, Alzheimer’s, and tumor growth and metastasis are all affected by various dysfunctions of Dr. Narayan Avadhanimitochondria and associated protein complexes, and our research focuses on the precise mechanisms of those dysfunctions in order to help develop more effective therapies.  To date, our research has included investigations into the mechanisms of alcohol, drug and hypoxia induced mitochondrial dysfunction affecting cytochrome c oxidase, and we were the first to suggest that certain protein complexes with chimeric targeting signals can be diverted to mitochondria, causing toxicity that can lead to Alzheimer’s disease.  We were also among the first researchers to describe the effects of mitochondrial respiratory distress on tumor growth and metastasis and have identified several important landmarks of the retrograde signaling that contributes to tumor progression.
  • Dr. Tracy Bale's Laboratory
    • Our lab’s research interests are centered on understanding the role of stress dysregulation in disease, and the sex differences that underlie disease vulnerability. We have developed mouse models relevant to neurodevelopmental disorders to study the interaction of genes and the Tracy Bale, PhD, Penn Vet Anatomyenvironment, assessing epigenetic mechanisms involved in sex-specific programming in the brain and other tissues, and the transgenerational effects via germ cell reprogramming. Many prenatal and early life signals regarding energy availability and stress are important in neurodevelopment. The neuroendocrine center of the brain, the hypothalamus, is particularly sensitive to perturbations during early development. Our research has determined that within this brain region, early gestational stress can disrupt mitochondrial programming, promoting dysfunction and stress sensitivity throughout life. The Bale lab’s research is supported by the National Institute of Mental Health (NIMH) and the Office of Research on Women’s Health at the NIH.
  • Dr. Ralph Brinster
    • Our lab studies the effects of aging on spermatogonial stem cells (SSCs)  and the cells that surround them, known as their niche. The aging process within these stem cells is a significant cause of declining fertility in all mammals, from mice to humans.  Our previous studies have shown that the decline in SSCs, which are comparatively long-lived, results primarily from a failure of the niche cells, and our research indicates that when transplanted from an older male into a younger male, SSCs generate more active SSCs, which suggests that these stem cells do not lose their capability to self-renew.  The modification of the niche cells, then, is a possible therapy for preserving stem cell activity, which has implications for therapeutic treatment of any tissues dependent on stem cell support.
  • Dr. Olena Jacenko
    • Dr. Olena JacenkoAging of the hematopoietic system is characterized by altered blood cell differentiation, deficient immune function and increased incidence of malignancies. Our laboratory proposes that these aging changes stem at least in part from aging of the hematopoietic niche within the chondro-osseous junction. The lab’s data maintain that the niche is comprised of extracellular matrix products unique to a subset of cartilage and bone cells. This hypothesis is being tested by iso-and heterochronic cell co-cultures, cell implants, bone marrow transplantations and establishment of mouse models.
  • Dr. Michael May
    • Our primary research interest is to identify the signaling pathways that regulate the activity of Nuclear Factor-kappa B (NF-kB), a protein that plays a key role in regulating the immune response to infection. Aberrant activation of NF-kB, which controls the flow of information from DNA to mRNA, may contribute to the development of chronic inflammatory diseases (like atherosclerosis and rheumatoid arthritis) and cancer.  Our research aims to determine the mechanistic basis of that activation, and we have developed several novel in vivo genetic models to investigate the effects of deleting NF-kb signaling in inflammatory disease development.  Our lab has also pioneered the use of cell-permeable peptides to target this process in chronic inflammatory diseases.  Dr. May’s laboratory is supported by the National Institutes of Heart, Lung and Blood.