Mitochondrial Function as a Therapeutic Target for Alzheimer's Disease

Speakers

M. Flint Beal, MD

Weill Medical College of Cornell University
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M. Flint Beal is an internationally recognized authority on neurodegenerative disorders. He is the Anne Parrish Titzell Professor in the Department of Neurology and Neuroscience at the Weill Medical College of Cornell University – New York Presbyterian Hospital.

Beal received his medical degree from the University of Virginia in 1976 and did his internship and first year residency in Medicine at New York – Cornell before completing his residency in Neurology at The Massachusetts General Hospital. He joined the neurology faculty at Harvard in 1983. Beal was Professor of Neurology at the Harvard Medical School and Chief of the Neurochemistry laboratory at Massachusetts General Hospital before moving to Cornell.

Beal's research has focused on the mechanism of neuronal degeneration in Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). He is the author or co-author of more than 400 scientific articles and more than 125 books, book chapters and reviews. He serves on the editorial boards of seven journals, including the Journal of Neurochemistry, the Journal of Neurological Sciences, Journal of Molecular Neuroscience, Experimental Neurology, and Neurobiology of Disease. Beal is a member of the Institute of Medicine of the National Academy of Sciences.

Jerry R. Colca, PhD

Metabolic Solutions Development Company
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Jerry Colca, PhD, is a co-founder, part owner, and president/chief scientific officer of Metabolic Solutions Development Company (MSDC; msdrx.com) in Kalamazoo, MI. Colca has spent his professional career studying the endocrine control of metabolism as relates to diabetes. He has a BS in Biology and an MS and PhD in Physiology and Biochemistry from the University of Houston where he studied the regulation of secretion of pancreatic hormones. His postdoctoral training at Washington University concentrated on the biochemistry of isolated pancreatic islets and the study of stimulus–secretion coupling in the control of metabolism.

Colca joined the Upjohn Company in 1984 to study to the mechanism of action of the thiazolidinediones and was instrumental in selection and development of pioglitazone hydrochloride (Actos®) as an anti-diabetic agent through Phase 2A clinical studies. The company formally known as Upjohn exited the insulin-sensitizing field in 1993. Colca remained with the Upjohn Company through the mergers with Pharmacia, Monsanto-Searle, and Pfizer until he retired from the merged company in 2005. During this time he was leader of diabetes discovery team in Kalamazoo, helped build a new diabetes discovery effort in Sweden after the merger with Pharmacia, and finally building a new targets discovery effort in St. Louis after the Pfizer merger. Colca has been interested in the mechanism of action of the insulin sensitizer TZDs from the early days of their discovery and especially in the safety and pharmacology of pioglitazone. In January of 2006, Colca co-founded MSDC with Rolf Kletzien to take advantage of their unique insight into these molecules.

Gary E. Gibson, PhD

Weill Cornell Medical College at Burke Medical Research Institute
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Gary E. Gibson received his BS degree in zoology and chemistry from the University of Wyoming. He received his PhD in physiology with emphasis in biochemistry and neuroscience at Cornell University. He did his postdoctoral work at UCLA and was on the faculty at UCLA. He then moved to Cornell University Medical College and Burke Medical Research Institute. He is currently professor of neuroscience, and is also a member of the graduate program in neuroscience at Cornell Medical College.

Gibson also served as the associate director of the Dementia Research Service. Gibson received the American Society for Neurochemistry award for outstanding young investigator. He has given lectures at many institutions and honorary lectures including the Deans hour at Cornell University Medical College, the NIH Director's Talk and the Visek Lectureship at the University of Illinois. He has served on over 25 NIH grant review panels and regularly reviews grants for the Alzheimer Association. He is a member of numerous scientific societies and was the secretary of the American Society for Neurochemistry. He has served(s) on the editorial board of several journals including Neurochemical Research, Neurochemistry International, the Journal of Neurochemistry, Mitochondria and the Journal of Alzheimer's Disease. He has been continuously funded by NIH grants for his whole career at Cornell/Burke. Within the last three years he has edited three volumes on the role of mitochondria and energy metabolism in the brain including a NY Academy of Sciences volume (#1147). Many of his 157 research papers and 76 reviews reflect his long research interest in the role of calcium and mitochondria in normal brain function as well as in Alzheimer's disease and other age-related neurodegenerative diseases.

William Kirby Gottschalk, PhD

Duke University
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W. Kirby Gottschalk has conducted extensive research on the effects of physiological and pharmacological perturbations on mitochondrial function, in both academia and private industry. He has investigated the mechanism of insulin regulation of mitochondrial function, including respiration and enzymes of the TCA cycle, oxidative phosphorylation and substrate transport, both in vivo with primary cells and ex vivo, with the goal of understanding how mitochondrial function contributed to insulin resistance. As senior investigator and section head in the Department of Metabolic Diseases at GlaxoSmithKine, Gottschalk headed a research group who designed and implemented mitochondrial functional assays for target validation, mechanism-of-action studies, and drug toxicology studies. As a member of the Alzheimer's team at GSK, he led the work that first showed that PPARγ agonists enhance cerebral glucose metabolism in vivo.

Stuart A. Lipton, MD, PhD

Sanford | Burnham Institute for Medical Research
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Stuart A. Lipton is professor and scientific director of the Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research at the Sanford | Burnham Institute for Medical Research. He is a professor at the Salk Institute, the Scripps Research Institute, and the University of California, San Diego. Educated at three Ivy League universities, Lipton is a research scientist and clinical neurologist. He completed his clinical and scientific training at Harvard as a postdoctoral fellow with Professor Torsten N. Wiesel when Wiesel won the Nobel Prize. Lipton then spent 25 years on the faculty at Harvard before moving to La Jolla in the fall of 1999.

He is best known for discovering the mechanism of action and contributing to the clinical development of the latest FDA-approved treatment for Alzheimer's disease (memantine/Namenda). His group also characterized the molecular pathways for protecting nerve cells by erythropoietin (a drug marketed for the treatment of anemia). Lipton and collaborator Stamler discovered the chemical reaction termed S-nitrosylation as a ubiquitous redox-regulator of protein function. Additionally, Lipton was the first to clone and characterize the transcription factor MEF2C, and showed that it is a redox-regulated master swtich for the generation of new nerve cells (termed neurogenesis) from human ESCs and iPSCs. Lipton's group has also shown that dysregulation of MEF2C is involved in the etiology of autism-spectrum disorders. In 2004, Lipton won the Ernst Jung Prize in Medicine, considered one of the top five or six medical prizes worldwide.

Tomas A. Prolla, PhD

University of Wisconsin-Madison
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Tomas A. Prolla received his BS in Biochemistry from the University of California at Berkeley in 1990, and his PhD from the Department of Molecular Biophysics and Biochemistry at Yale University in 1994. He is currently professor of genetics & medical genetics at the University of Wisconsin – Madison. Prolla is internationally recognized for research in two main areas, gene expression changes associated with aging, and the role of mitochondria in aging. Prolla's research group was the first to employ large-scale gene expression profiling using DNA microarrays to the analysis of aging and its retardation by caloric restriction. Prolla has also generated a widely used mouse model of aging, mice with a defective DNA polymerase gamma that result in the accumulation of mitochondrial DNA mutations. Recently, Prolla has focused on the role of mitochondria and associated apoptotic signaling in specific aspects of aging, including age-related hearing loss and sarcopenia. Prolla has also co-founded LifeGen Technologies in 2001, a company focused on the use of transcriptional markers of aging and caloric restriction in the development of aging interventions.

P. Hemachandra Reddy, PhD

Oregon Health & Science University
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P. Hemachandra Reddy is an associate scientist in the Division of Neuroscience at the Oregon National Primate Research Center of Oregon Health and Science University (OHSU). He received his BSc and MSc in biology from Sri Venkateswara University, Tirupati, India. He received an MPhil in human cytogenetics from Delhi University. He was a commonwealth scholar (1990–1993) before receiving his PhD (1994) in human genetics from London University. He did his postdoctoral training (1995–2000) at the National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland. After his postdoctoral training, he joined the OHSU–Neurological Sciences Institute Faculty in July 2000, and joined the primate center in July 2008.

Reddy has received several awards and honors, including Commonwealth Scholarship from Commonwealth Commission, Great Britain; Fellows Award for Research Excellence from National Institutes of Health; Alzheimer Award from the Journal of Alzheimer's Disease, and Technology Innovations Award from Oregon Health and Science University. Reddy is a standing member of the Veteran Affairs Merit Review Study Section, and has served on several NIH study sections, including the section Cell Death in Neurodegeneration. Reddy is an editorial board member for seven journals. Reddy is an expert in mitochondrial biology and function, gene expression analysis, and neurodegenerative diseases. The research focus in the Reddy laboratory is on understanding molecular and cellular bases of neurodegenerative diseases such as Alzheimer's disease (AD). Currently, the Reddy laboratory is focusing on unraveling the connection between amyloid beta and synaptic damage, and amyloid beta and mitochondrial oxidative damage in AD. The Reddy laboratory is funded by National Institutes of Health, Alzheimer's Association, Vertex Pharmaceuticals, Medivation, and KaloBios Pharmaceuticals.

Hiromi Sesaki, PhD

Johns Hopkins University School of Medicine
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Hiromi Sesaki received his PhD from the Department of Physiology at Osaka University in Japan. He is currently assistant professor of cell biology at the Johns Hopkins University School of Medicine. The laboratory of Dr. Sesaki is studying mitochondrial dynamics and membrane biogenesis using yeast and mice.

Douglas C. Wallace, PhD

University of California Irvine
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Douglas C. Wallace is the Donald Bren Professor of Molecular Medicine, director, ORU for Molecular and Mitochondrial Medicine and Genetics (MAMMAG), and professor of biological chemistry, ecology and evolutionary biology, and pediatrics. Wallace has been a pioneer in the study of human mitochondrial genetics and the role of mitochondrial DNA variation in human evolution, disease, cancer, and aging. In the 1970s Wallace defined the basic principles of human mitochondrial DNA genetics, demonstrating that the human mitochondrial DNA encodes heritable traits, is maternally transmitted, has a high mutation rate, that intracellular mixtures on mutant and normal mitochondrial DNA are common and can segregate randomly during both mitotic and meiotic cell division, and that the clinical phenotype of a mutation depends on the severity of the mitochondrial defect and the reliance of each individual tissue on mitochondrial energy production.

Once Wallace had defined the basic principles of mitochondrial DNA genetics, he applied these principles to the investigation of human origins and disease. Wallace also identified the first maternally inherited mitochondrial DNA diseases and has subsequently shown that deleterious mitochondrial DNA mutations are common and result in a plethora of complex multi-system diseases which encompasses all of the clinical phenotypes associated with aging, including neurological problems such as deafness, blindness, movement disorders, and dementias; cardiovascular disease; muscle degeneration and pain; renal dysfunction; endocrine disorders including diabetes and cancer.

Shi Du Yan, MD

Taub Institute of Columbia University
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Shi Du Yan (Shirley ShiDu Yan) is a professor in the Department of Pathology and Surgery at the Taub Institute for Research on Alzheimer's disease and the Aging Brain, Columbia University, New York. Yan's research focuses on investigating cellular and molecular mechanisms of cell stress and survival in neurodegenerative disorders relevant to Alzheimer's disease. She was the first to identify the specific cellular (RAGE) and mitochondrial (ABAD and cyclophilin D) targets of amyloid-beta peptide (Aβ) and found the evidence of Aβ-mediated mitochondrial, synaptic, and neuronal dysfunction. Her recent studies highlight the significant impact of mitochondrial Aβ on neuronal stress and cognitive decline relevant to the pathogenesis of Alzheimer disease. Yan and her research team's findings have been published in worldwide leading journals including Nature, Science, Nature Medicine, Proceeding of National Academy Sciences, and in first class professional journals. Yan has authored 140 publications. Her research project is supported by National Institute of Health and Alzheimer's Association. She received several awards including the Zenith Fellow Award from the Alzheimer's Association in 2005.

Xiongwei Zhu, PhD

Case Western Reserve University
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Xiongwei Zhu received his BS in 1995 and MS in 1998 from the Department of Biochemistry at Wuhan University in China. He received his PhD in 2002 from the Department of Pathology at Case Western Reserve University. He became assistant professor in 2004 and rose to associate professor in 2009. Zhu's research focuses on the mitochondrial dysfunction in Alzheimer disease and other neurodegenerative diseases and his research program is supported by National Institute of Health, Alzheimer's Association and American Parkinson Disease Association. Zhu is the recipient of several awards including the Junior Faculty Award from 9th International Conference on Alzheimer Disease and Parkinson Disease (2009), and the Young Investigator Lectureship Award from the International Society for Neurochemistry (2009).

Catherine Zandonella

Catherine Zandonella is a science writer based in New York City, covering such topics as environmental science, public health, and applied technology. She has a master's degree in public health from the University of California, Berkeley. Zandonella has written for a number of publications, including New Scientist, The Scientist, and Nature.