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Kerry O'Banion, M.D., Ph.D.
Associate Professor:
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Kerry O'Banion is the principal investigator on two NIH research grants and an NIH training grant for the Medical Scientist Training Program (MSTP). He holds three U.S. patents, and he has had several collaborations with industry, including Monsanto and Roche Bioscience. In addition, Kerry is on the editorial board of the Journal of Neuroinflammation; has published 48 refereed papers, two of which have been cited more then 450 times. He has served on the thesis committees of more than 20 students, several of which have received Ph.D.s under his direct guidance. In addition, he has trained several postdoctoral fellows and sits on an NIH study section (CNBT-1, formerly BDCN-4).
The contributions that Kerry has made to science and education read like those of which young scientists dream. Read on and you'll see what we mean.
Kerry was born in Florida, where he received great mentorship from his parents. Both have advanced degrees, with his father earning a Doctorate in Education from Florida State University and his mother earning a Master’s degree in Education. His father, Terry (click here for a similar focus on Kerry's dad), is also well known in higher education and has had several leadership roles in the development of Community Colleges throughout the country. It is not surprising that when Kerry's dad took a professorship at the University of Illinois, that Kerry would eventually attend the Champaign-Urbana campus, obtaining all three of his degrees there.
Kerry's Bachelor's degree (1980) was in Biology with a Pre-Med curriculum. He had always been attracted to scientific research, and during his undergraduate years, he developed a keen interest in the application of science and medicine towards improving human health.
Prairie Vole Pair-Bonding
Kerry was introduced to research during his junior year when he began work in the Psychology Department with Sue Carter-Porges on a project which later developed into his Senior Honors Thesis. This work examined the social interactions and hormone chemistry related to pair-bonding behavior in prairie voles. As Kerry explains, these animals are unique among rodents because they establish monogamous relationships. Kerry's undergraduate work on this project involved the maintenance of a colony of 50 prairie voles on which he completed behavioral experiments to examine mate selection and breeding behaviors. This work ultimately established that male pheromones influence the female's selection of an appropriate mate.
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Kerry and M.D./Ph.D. student Sol Shaftel. Sol is co-advised by John Olschowka and Kerry O'Banion in the |
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Papilloma Viruses and Cancer
With his undergraduate thesis work fueling an interest in neuroscience and the desire to apply science to medicine, Kerry entered the Medical Scholars M.D.-Ph.D. Program at the University of Illinois at Champaign-Urbana in 1980. Driven to learn molecular biology techniques, Kerry noted in the early 1980s that this type of training could be obtained only within a Microbiology or Biochemistry department. Therefore, he chose to obtain his Ph.D. in the Microbiology department, concentrating on research in molecular virology. His thesis work was largely related to the cloning of novel papilloma (wart) viruses. With his advisors, Drs. Reichmann and Sundberg, Kerry cloned 6 novel viruses from a number of species, including dogs, rabbits, mice, and parrots. In fact, he cloned viruses from Colobus monkey, which had a venereal wart.
While Kerry was cloning his viruses, scientists in Germany and at the NIH were just beginning to establish that human papilloma viruses (HPV) were associated with cervical cancer. In addition to novel papilloma virus cloning, Kerry's thesis research examined how a wart converts into a cancer of an epithelial origin. This was achieved by examining changes in the morphology of mouse fibroblast cells after transfection with viral clones. Today, we recognize approximately 60 human papilloma viruses, and of those, approximately 10 have the potential to cause cancer.
The Discovery of COX-2
After the completion of his Ph.D. and M.D. degrees, Kerry came to the University of Rochester in 1987 to continue his work with papilloma viruses. Working with Don Young, a Professor in the Departments of Medicine and Biochemistry with major interest in endocrinology, Kerry expanded his knowledge of molecular biology. Don was studying how messenger RNA and protein expression change in different types of cancers utilizing pioneering methods in the nascent field of study now referred to as proteonomics. Kerry participated in three inter-related projects in the lab. First, Kerry looked at papilloma virus-induced cell transformation, identifying novel genes in bovine papilloma virus and examining their impact on cell protein changes. A second project in the laboratory involved the study of the genetic regulation of the glucocorticoid-induced protein, glucocortin. In a third project, giant 2D gels were used to examine the genetic and protein composition of cancers induced by viral transfection of fibroblast cells.
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O'Banion, M. K. and D. A. Young. 1991. Bovine papillomavirus type 1 alters the processing of host glucose- and calcium-modulated endoplasmic reticulum proteins. J. Virol. 65:3481-3488. |
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O'Banion, M. K., H. B. Sadowski, V. Winn, and D. A. Young. 1991. A serum- and glucocorticoid-regulated 4 kb mRNA encodes a cyclooxygenase-related protein. J. Biol. Chem. 266:23261-23267. |
The laboratory was interested in the study of genes that were regulated by glucocorticoid hormones. In addition to reducing inflammation, glucocorticoids also suppressed cell growth in tissue culture, a key feature that is useful in the treatment of cancers like lymphoma. While examining the 2D gels used to characterize the mRNA and proteins that accompany changes in cell growth or morphology, Kerry and his lab partners identified one spot on the gels that consistently appeared in their cancer models. This spot appeared to increase quickly in association with oncogene activation or growth induction. However, if glucocorticoids were present in the cultures, they abrogated the increase in the production of the protein that corresponded to this spot on the gel. Hank Sadowski, a student in the lab, remembered a paper he'd seen four years earlier that happened to show a spot on a gel that looked similar. This led the group to hypothesize that the protein that they were detecting was cyclooxygenase. To learn more about the discovery, you might want to view Kerry's video.
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Antibodies that were cross-reactive to cyclooxygenase confirmed that their hypothesis was indeed correct and led Don's laboratory to pursue the study of this protein at the RNA level. They identified two mRNAs for cyclooxygenase termed COX-1 and COX-2. Because of the known importance of these enzymes, which make prostaglandins in inflammation, Kerry went on to examine regulation of COX-1 and COX-2 in human white blood cells treated with the proinflammatory cytokine interleukin-1ß (IL-1ß). He showed dramatic upregulation of COX-2 by IL-1ß and suppression of expression by the anti-inflammatory actions of glucocorticoids. This firmly established the importance of COX-2 as a relevant target for anti-inflammatory therapies. The growth factor and oncogene work also suggested a role for COX-2 in cancer.
The laboratory set out to develop an assay that distinguished between the activities of COX-1 and COX-2, reasoning that such an assay could be used to screen compounds and identify anti-inflammatory drugs selective for COX-2. In targeting COX-2 for inhibition, they hoped to reduce some of the serious side effects associated with drugs such as aspirin and ibuprofen that inhibited both COX-1 and COX-2. With this goal in mind, they cloned and sequenced mouse and human versions of the enzyme, developed a series of cell lines for use in drug screening assays, and filed patents targeting this enzyme for treating inflammation in people.
During this time, Kerry collaborated with 5-6 people in other departments running 2D gels. He collaborated with people from Immunology, Infectious Disease and Nephrology, and he worked with at least two investigators in Neuroscience, Paul Coleman and Marty Bohn. With the COX-2 patent marking the near completion of his postdoctoral fellowship, Kerry's fascination with neuroscience grew as he contemplated positions with different universities and pharmaceutical companies. However, the interactions, collaborations, and work environment led Kerry to choose to remain at the University of Rochester.
Neuroinflammation in Alzheimer's Disease & Brain Injury
At the time, it was just being recognized that diseases such as Alzheimer's had an attribute that had been pretty much ignored, an attribute we now call Neuroinflammation. Unlike the immune system attack on brain tissue seen in Multiple Sclerosis, the neuroinflammation associated with Alzheimer's Disease was viewed as a local tissue reaction. As such, it was largely ignored by immunologists and neuroscientists. However, information accumulating in a few labs at the time indicated that this might be an important factor in Alzheimer's Disease pathogenesis. In particular, people who took anti-inflammatory drugs appeared to reduce their risk for Alzheimer's.
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Yermakova, A. V., and M. K. O'Banion. 2001. Downregulation of neuronal cyclooxygenase-2 expression in end stage Alzheimer's disease. Neurobiol. Aging. 22:823-836. |
In 1991, Kerry was offered a faculty position under Paul Coleman, who had a special grant called a LEAD award: Leadership and Excellence in Alzheimer's Disease Research. This allowed Kerry to move into Neuroscience. At the time, he was a Primary Faculty Member in the Department of Neurology and a Secondary Faculty Member in Neurobiology. Immediately, he continued his research on neuroinflammation, hypothesizing that the drugs inhibiting COX might be beneficial in treatment of Alzheimer's Disease. Ultimately, his clear calling was to work on cyclooxygenase and prostaglandins.
His initial experiments were done in cell cultures. He was interested in the production of prostaglandins in response to inflammatory stimuli, but also, he asked: what are the downstream events following that? As Kerry states, "We're still asking questions about how a pro-inflammatory stimulus drives prostaglandin production and then signals a stream of events that regulate and modulate the expression of other genes important for the inflammatory response. We all know if you take these drugs and you inhibit the prostaglandins, that you get rid of the swelling or the pain. So we're trying to understand this process in the context of the brain."
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Hurley SD, O'Banion MK, Song DD, Arana FS, Olschowka JA, Haber SN. Microglial response is poorly correlated with neurodegeneration following chronic, low-dose MPTP administration in monkeys. Exp Neurol. 2003 Dec;184(2):659-68. |
In 1993-1994, Kerry teamed up with John Olschowka to form a long-lasting collaboration. For a number of years, they've been focusing on the actions of interleukin-1, a key proinflammatory cytokine that influences neuroinflammation in conditions ranging from head trauma to Alzheimer's Disease. Through collaborations with other investigators, many of which are at the University of Rochester, Kerry has helped the field gain insight into neuroinflammatory processes that occur in a variety of models of diseases such as epilepsy, Parkinson's disease, amyotrophic lateral sclerosis (ALS or Lou Gherig's Disease), and in the normal aging brain. Some of these collaborators include Sean Hurley, Suzanne Haber, Jackie Williams, Paul Okunieff, and Lisa Opanashuk.
Kerry has also had great impact on the educational environment of the University of Rochester through his contributions to teaching and course development/directorship with both the medical and graduate student curricula. He is a course co-director of Mind, Brain, and Behavior I and II, laboratory instructor in Cellular Neuroscience (NSC 512), co-director of a new course on Neuroinflammation (ANA 513), and director of the M.D./Ph.D. Journal Club course entitled "Scientific Reasoning in Medicine". In fact, Kerry is Co-Director of the MD/PhD Program at Rochester and Principal Investigator of the Medical Scientist Training Program (MSTP) grant. Rochester is one of only 40 US Medical Schools to have this award. His service on a number of intramural and national committees includes the Joint AMSNDC/AAN Working Group on Basic Science Curriculum Guidelines for US Medical Schools, which he co-chairs.
Current students in Kerry's laboratory include Ph.D. student Yuri Shapovalov and M.D./Ph.D. student Sol Shaftel. Mary Maida received her Ph.D. in Kerry's lab and has continued as a postdoctoral fellow. The current lab group is rounded out by Technical Assistant Joanne Daeschner and undergraduate Sharon Paige. Recent students and postdoctoral fellows have included Stephanos Kyrkanides and Sean Hurley, both of whom have continued their careers here at the University of Rochester and maintain collaborations with Kerry.
Students in Kerry O'Banion's laboratory
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Yuriy Shapovalov: |
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Joanne Daeschner: |
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Kerry with |
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Kerry and his wife, Dorothy Petrie, live in the Mendon Ponds area. Kerry's son, Colin, lives in Rochester and will be starting college next year. Dorothy is a music teacher in the Greece public school system. To relax, Kerry and Dorothy enjoy gardening, cooking, and visiting family. When he's feeling adventurous, Kerry goes into the wild outdoors to hike and camp and dream about fishing. |
Noteworthy and Recent Publications
- O'Banion, M. K., H. B. Sadowski, V. Winn, and D. A. Young. 1991. A serum- and glucocorticoid-regulated 4 kb mRNA encodes a cyclooxygenase-related protein. J. Biol. Chem. 266:23261-23267.
- O'Banion, M. K., V. D. Winn, and D. A. Young. 1992. cDNA cloning and functional activity of a glucocorticoid-regulated inflammatory cyclooxygenase (griPGHS). Proc. Natl. Acad. Sci. USA 89:4888-4892.
- O'Banion, M. K. 1999. Cyclooxygenase-2: Molecular biology, pharmacology and neurobiology. Crit. Rev. Neurobiol. 13:45-82.
- Yermakova, A. V., and M. K. O'Banion. 2001. Downregulation of neuronal cyclooxygenase-2 expression in end stage Alzheimer's disease. Neurobiol. Aging. 22:823-836.
- Kyrkanides, S., A. H. Moore, J. A. Olschowka, J. C. Daeschner, J. P. Williams, J. T. Hansen and M. K. O'Banion. 2002. Cyclooxygenase-2 modulates brain inflammation-related gene expression in CNS radiation injury. Mol. Brain Res. 104:159-169.
- Moore, A. H. , J. A. Olschowka, J. P. Williams, S. L. Paige and M. K. O'Banion. 2004. Radiation-induced edema is dependent on cyclooxygenase-2 activity in mouse brain. Radiat. Res. 161:153-160.
- Moore, A.H., J. A. Olschowka and M. K. O'Banion. 2004. Cyclooxygenase-2 activity mediates expression of membrane- and cytosolic-associated prostaglandin E 2 synthases following intracerebral administration of IL-1 b . J. Neuroimmunol. 148:32-40.
Patents
- US Patent 5,807,733. Mammalian Prostaglandin H Synthase-2 Fusion Proteins. M.K.O., Donald A. Young, and Virginia D. Winn -- Co-Inventors.
- US Patent 5,837,479. Screening Assays for Inhibitors of Mammalian Prostaglandin H Synthase-2. M.K.O., Donald A. Young, and Virginia D. Winn -- Co-Inventors.
- US Patent 6,048,850. Method of Inhibiting Prostaglandin Synthesis in a Human Host. M.K.O., Donald A. Young, and Virginia D. Winn -- Co-Inventors.