Castora, Frank J.

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  • A major interest of my laboratory involves the role mitochondrial function plays in aging and in the development of Alzheimer's Disease (AD). A number of reports link compromised energy metabolism to AD. An important mitochondrial enzyme, cytochrome oxidase, has significantly reduced activity in the brains of AD patients. Since three of the subunits of cytochrome oxidase are encoded on mtDNA, an AD-associated decrease in cytochrome oxidase activity could result from a mutation in these mtDNA-encoded genes. I have obtained autopsy-confirmed AD brain samples as well as age-matched controls and screened these samples for mutations in mtDNA. My laboratory group has identified a mutation that occurs in a higher frequency in AD brains than in age-matched controls. We are in the process of characterizing the effect of this mutation on mitochondrial function. One of the approaches we have taken is to examine the effect of this mutation on the expression of a subset of mitochondrial genes important for energy production and mitochondrial biogenesis. In collaboration with Dr. Randolph Coleman at the College of William and Mary, we are using this expression data to generate a testable, mathematical model for AD.



    A second area of interest in my laboratory is the role that mitochondrial function may play in the process of fertilization and also of endometriosis. I have collaborated with Dr. James Swanson formerly of Old Dominion University and Dr. Howard Jones of EVMS to investigate the role of mitochondria in oocyte health. We are currently using a hamster model for our studies on fertilization. Oocytes removed from female hamsters are analyzed for mtDNA number and mutations and ATP levels are determined. We have patented a procedure termed APMM (Autologous Platelet Mitochondrial Microinjection) to introduce fresh, purified mitochondria from hamster platelets back into oocytes recovered from aged hamsters to enhance fertilizability in older animals. We are currently improving that procedure as well as looking at ways to use supplements to further enhance the positive impact of APMM.

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  • Professor

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  • Frank J. Castora, PhD

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