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2006
| Monday, October 23, 2006 NOON | |||||||||||||||||||||||||||
Edward L. Orr, Ph.D.Biomedical Sciences ProgramSchool of Natural and Health Sciences Barry University Miami Shores, Florida 33161-6695 Office Phone: 305-899-3680 E-Mail: eorr@mail.barry.edu Title: Effects of Head Injury on Dural Mast Cells, Cerebral Cortical Histamine, and Cerebrovascular Permeability Date: Monday, October 23, 2006 VCOM Host: Dr. Hara Misra |
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Professional Summary:Edward L. Orr, Ph.D. received his Bachelor of Science degree from Cleveland State University in Cleveland, Ohio in 1970 and his Ph.D. from the University of California in Berkeley, California in 1975. After post-doctoral stints at the Dight Institute for Human Genetics at the University of Minnesota and at the Waisman Center for Mental Retardation and the Wisconsin Regional Primate Research Center, both at the University of Wisconsin in Madison, Wisconsin, he joined the faculty in the Department of Anatomy, Texas College of Osteopathic Medicine (now the University of North Texas Health Science Center at Fort Worth; UNTHSC) in 1979. While there, he taught Human Embryology and Medical Neuroscience to first year medical students for over 23 years while carrying out an active research program on the significance and role of histamine and, subsequently, CNS-associated mast cells, in the brain, especially as related to the development and progression of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. After "retiring" from UNTHSC as an Associate Professor in 2001, he then moved with his then wife and their two young children to Portland, Maine where he joined the physiology faculty at the University of New England College of Osteopathic Medicine in Biddeford, Maine for a year before returning to Texas where he then served on the faculty at Texas Womens University in Denton, Texas before joining the faculty in the School of Natural and Health Sciences at Barry University in Miami Shores, Florida in 2004 as an Associate Professor in the Graduate Biomedical Sciences Program. At Barry University, he teaches Neuroanatomy, Histology, Human Embryology, and Endocrinology to Masters students preparing for entry into medical or dental school, as well as Neuroanatomy to first year students in the Podiatric Medicine Program. He has also re-initiated his research activities where he is evaluating the significance and roles of meningeal and other CNS-associated mast cells in response to various forms of head or brain injury. This research is being carried out in collaboration with colleagues at the University of Miami and the Miami Project to Cure Paralysis in nearby Miami, Florida. Abstract:In previous research, I had demonstrated that meningeal (dural) mast cells are activated by unilateral cryogenic injury of the mouse head and brain, and that such injuries are accompanied by breakdown of the blood-brain barrier, cerebral edema, and an accumulation of mast cell-derived histamine in the injured cerebral cortex; however, the edema and permeability effects of such cryogenic injuries were not attenuated in mast cell-deficient mice, even though the increase in cerebral cortical histamine did not occur (Orr & Pace, Cryogenic lesions induce a mast cell-dependent increase in cerebral cortical histamine levels in the mouse. Neurochem. Pathol. 8: 43-51. 1984). Disappointed with the apparent lack of significant involvement of dural mast cells and mast cell-derived histamine in this type of brain injury, I discontinued this research direction until recently. I now report that a much more moderate type of head injury (initially, a unilateral craniotomy and, subsequently, simply cutting grooves in the skull) also activates mast cells in the underlying dura mater and that this activation of dural mast cells is accompanied by increases in histamine levels and pial vascular permeability in the subjacent cerebral cortex. Moreover, prior administration of a specific histamine H2-receptor antagonist (zolantidine) significantly and dose-dependently decreases the increase in pial vascular permeability. This research demonstrates that a relatively mild skull injury that does not directly injure the brain results in significant effects on the underlying brain that are mediated in whole or in part by dural mast cells and their released mediators. |
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| Monday, October 9, 2006 NOON | |||||||||||||||||||||||||||
Dr. Rakesh SharmaAddress: A160 COE NHMFL FSU, 1800 E. Paul Dirac Dr., Tallahassee, FL 32310-3706Telephone: 850-410-6149 Fax: 850-410-6150 Title: What we can Measure by Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy for Quantitative Anatomy Date: Monday, October 9, 2006 VCOM Host: Dr. Hara Misra |
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Current Research Interests:
Abstract:Quantitative Anatomy is emerging as rapid tool of Radioimaging in both clinical and biomedical research to monitor the effect of drug. Multimodal techniques like Magnetic Resonance Imaging with spectroscopy, Positron Emission Tomography and Molecular imaging provide non-invasive quick insight of tissue characterization and its tissue type with its cellular metabolic details in neurodegenerative disorders of Alzheimer's Disease, Epilepsy, Multiple Sclerosis after Promiscol? therapy. Localized diseases like Atherosclerosis plaque and cardiovascular wall thickening can be measured to evaluate the effect of Lovastatin®. With advanced magnetic resonance imaging operating at high field of 21 Tesla, it has become possible to visualize details of tissues at cellular level after drug therapy. |
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| Tuesday, September 19, 2006 NOON | |||||||||||||||||||||||||||
David J. Mokler, Ph.D.Department of PharmacologyUniversity of New England College of Osteopathic Medicine Address: 11 Hills Beach Road, Biddeford, Maine 04005 Title: Investigations of the Effects of MDMA (Ecstasy) on Neuronal Serotonin and Dopamine Using In Vivo Microdialysis Date: Tuesday, September 19, 2006 VCOM Host: Dr. Hara Misra |
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Abstract:MDMA (Ecstasy) is a commonly used drug of abuse. Of great concern has been the neurotoxic effects of MDMA on serotonergic neurons in animals exposed to single high doses or multiple low doses of MDMA. Data from animal studies has shown that this neurotoxicity can be avoided if the animals are pretreated with a selective serotonin reuptake inhibitor such as fluoxetine (Prozac). It has been reported that human MDMA users have pretreated with fluoxetine in an attempt to avoid this possible neurotoxic effect. Furthermore, the SSRIs are commonly prescribed drugs. We have investigated the interactions between MDMA and fluoxetine in terms of extracellular serotonin and dopamine using in vivo microdialysis. In vivo microdialysis allows us to monitor the extracellular concentrations of serotonin and dopamine in the awake, behaving animal. We have examined the extracellular concentrations of serotonin and dopamine in rats ten days after receiving a toxic dose of MDMA alone or pretreated with fluoxetine. MDMA alone decreased extracellular serotonin in the striatum and to a lesser extent in the prefrontal cortex, but did not alter extracellular dopamine in either area. Fluoxetine prevented this effect of MDMA on extracellular serotonin. The combination of fluoxetine and MDMA however produced a decrease in extracellular dopamine in both the striatum and prefrontal cortex. Early studies suggest that this may in fact be a switch in neurotoxicity from serotonin to dopamine neurons. Education:
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Publications:The following represent the recent work of Dr. Mokler which consists of 55 peer reviewed papers and over 100 abstracts.
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| Monday, September 11, 2006 NOON | |||||||||||||||||||||||||||
Robert R. Luedtke, Ph.D.Professor, Department of Pharmacology and NeuroscienceDepartment of Pharmacology and Neuroscience University of North Texas Health Science Center Address: 3500 Camp Bowie, Fort Worth, TX 76107 Telephone: (Office) 817-735-2611 (Fax): 817-735-2091 Email: rluedtke@hsc.unt.edu Title: Development of D3 Dopamine Receptor Subtype Selective Compounds Date: Monday, September 11, 2006 VCOM Host: Dr. Hara Misra |
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Abstract:The three dopaminergic pathways in the mammalian brain are the nigrostriatal, the mesocorticolimbic and the tuberoinfundibular pathways. Alterations in the dopaminergic pathways are thought to be involved in the pathogenesis of neurological and neuropsychiatric disorders, including Parkinson's Disease and schizophrenia. Modulation of the dopaminergic pathways is also thought to occur following acute or chronic abuse of cocaine and amphetamines. Molecular genetic studies have defined two types of dopamine receptors, the D1-like (D1 and D5 receptor subtypes) and D2-like (D2, D3 and D4 receptor subtypes) receptors based upon structural and pharmacological similarities. Because of the high degree of homology between D2 and D3 receptor binding sites, it has been difficult to obtain compounds that can bind selectively to either the D2 or the D3 dopamine receptor subtypes. However, we have recently developed D2 and D3 dopamine receptor selective compounds that we hope will be useful pharmacologic tools to precisely define the role of these two D2-like receptor subtypes in a variety of experimental physiological and behavioral situations. The seminar will discuss our research on the development and pharmacological characterization of D2 and D3 receptor subtype selective compounds of varying intrinsic activity. |
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| Tuesday August 22, 2006 NOON | |||||||||||||||||||||||||||
Yunbo Li, MD, PhDAssociate Professor of Medicine and PharmacologyAssociate Director, Center for Environmental & Smoking Induced Disease The Ohio State University College of Medicine and Public Health Columbus, Ohio 43210 Title: Pharmacological Upregulation of Cardiovascular Antioxidants & Phase 2 Enzymes: Mechanisms and Chemoprotection
Date: Tuesday August 22, 2006 VCOM Host: Dr. Hara Misra |
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Professional Summary:Dr. Li received an MD degree from Shandong Medical University, and a PhD degree in Toxicology/Pharmacology from The Johns Hopkins University. Dr. Li was a visiting scientist in the University of Sydney, Australia, and University of California at Berkeley from 1990 to 1991. Then, he completed a postdoctoral fellowship at The Johns Hopkins University. Dr Li toke his first tenure-track faculty position as an assistant professor of pharmaceutical sciences (pharmacology/toxicology) at St. John's University College of Pharmacy in 2000. He was promoted to an associate professor at the same institute in 2003. In January of 2005, Dr. Li joined The Ohio State University College of Medicine and Public Health. He is currently an associate professor of medicine and pharmacology. He is also the associate director of the Center of Biomedical Technology for the Study of Environmental and Smoking Induced Diseases at The Ohio State University. Dr. Li has published 73 peer-reviewed articles, and written a number of book chapters. He has received numerous institutional and national awards. Dr. Li's research is supported by NIH grants. The current research in his laboratory focuses on the free radical mechanisms of tissue injury and development of pharmacological/chemoprotective strategies for intervention of free radical-mediated disease process. Abstract:Cardiovascular disease (CVD) remains the number one cause of death in the United States. Considerable evidence supports a causal role for oxidative and electrophilic species in the pathophysiology of various forms of CVD, including myocardial ischemia-reperfusion injury, atherosclerosis, and drug-induced cardiotoxicity. As such, extensive studies have focused on use of exogenous antioxidative compounds, including antioxidant vitamins to prevent or retard the oxidative process underlying CVD. However, clinical trials on use of individual antioxidative compounds, including vitamin E, in the intervention of cardiovascular events have yielded conflicting results, pointing to the limitations associated with using exogenous antioxidants in the management of CVD. We propose a novel strategy for protecting against cardiovascular pathophysiology through drug/chemoprotectant-mediated coordinated upregulation of endogenous antioxidants/phase 2 enzymes in cardiovascular tissue. The coordinated actions of a series of cellular antioxidants/phase 2 enzymes are essential for efficient detoxification of oxidative and electrophilic species. The long-term objective of our research is to develop rational protective/therapeutic strategies to prevent, retard, or even reverse the oxidative degenerative process underlying cardiovascular disorders. Such strategies rely on a profound understanding of the pharmacological inducibility of cardiovascular antioxidants and phase 2 enzymes, and the underlying molecular mechanisms. Suggested reading:
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| Thursday July 6, 2006 NOON | |||||||||||||||||||||||||||
Harihara M. Mehendale, Ph.D.Professor and Kitty DeGree Chair in Toxicology Title: Liver tissue repair, survival factors and adaptation to injury Address: 207 Winterpark Drive, West Monroe, LA 71292, USA Date: Thursday July 6, 2006 VCOM Host: Dr. Hara Misra |
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Background:Dr. Mehendale received his M.S. and Ph.D. degrees from the Toxicology Program at North Carolina State University. He received his postdoctoral training at the University of Kentucky and at the National Institute of Environmental Health Sciences (NIEHS), before joining NIEHS as a Staff Fellow. In 1975, he joined the University of Mississippi Medical Center as Assistant Professor, rose through the academic ranks to full Professor in 1980. He joined the University of Louisiana at Monroe (ULM) in 1992. His research interests span across pulmonary, hepatic, renal and general toxicology of medicinal, industrial and environmental chemicals. His current area of research emphasis involves understanding the role of tissue repair in the ultimate outcome of tissue injury, the mechanisms in control of cell division and tissue repair as well as the molecular events keying these mechanisms. Current research is focused on the impact of age, diabetes, and diet restriction on toxic effects, mechanisms of progression and regression of injuries, and potential adverse health effects of exposure to combinations of chemicals. He has authored over 275 original research and review articles, as well as book chapters. Dr. Mehendale has received several Honors and Awards for his research and scholarly contributions. In 1988, he received the "Burroughs Wellcome Scholar in Toxicology" award given by the Society of Toxicology, U.S.A. In 1993, he received the Zeneca International Travel Award. In 1995, he was named outstanding researcher at ULM and received the "Researcher of the Year" Award. In 1996, the American Association for the Advancement of Science (AAAS) elected him "Science Fellow". In 1999, he received the Best Paper Award for best paper published in Toxicology and Applied Pharmacology. In 2001, received the Society of Toxicology??s Education Award for his eminent contributions to education in toxicology. Summary:Liver injury initiated by either the parent drug or its reactive metabolite(s), is known to progress in disease or other physiological states. While we know a great deal about how injury is initiated by drugs, a solid understanding of how injury may progress or regress is lacking. Recent studies reveal that many events driven by liver biology determine the latter. Progression can result due to destructive action of hydrolytic enzymes, "death proteins" leaking out of necrosed cells on the neighboring partly affected or unaffected cells, thereby setting off a self-perpetuating expansion of injury. Once necrosis is initiated by mechanism-based events, this process occurs even in the absence of the necrogenic drug. Calpain and c-phospholipase A2 (cPLA2) are examples of such hydrolytic 'death proteins'. Compensatory mechanisms such as cell division and over-expression of survival factors by the newly divided cells can prevent this onslaught by the death proteins and expansion of injury. Failed or delayed cell division, as in the case of high doses, or in disease, leads to expansion of injury. Autoprotection and heteroprotection models indicate that stimulation of cell division and tissue repair are critical in overcoming life-threatening liver injury suggesting that adaptive mechanisms can be activated in the liver by priming. Diabetes is known to sensitize liver to hepatotoxicity. Diabetic rats (type I & type II) are highly sensitive to hepatotoxicity due to impaired compensatory cell division in the diabetic state. However, even in the diabetic state, animal experiments show that it is possible to stimulate efficient cell division by priming and protect the diabetic animals from life-threatening liver toxicity, by overcoming the acute liver failure (ALF)-bound injury. In stark contrast to the diabetic rats, diabetic mice (type I & type II) are resilient to drug-induced hepatotoxicity. Unfortunately, this model has not been investigated enough to find out what we can learn from the mouse about survival strategies. Although much remains to be learned about the murine strategy for survival, what we know from drug toxicity models is that mice are able to compensate rapidly by early and robust stimulation of cell division. Moreover, subchronic priming exposure to chloroform for 30 days protect mice from a subsequent dose of chloroform that normally cause ALF and death, due to prompt stimulation of cell division as an adaptive mechanism. What we learn from these experimental models provide us clues that may be exploited to modify our approaches in dealing with drug-associated liver toxicities. Suggested Reading:
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| Wednesday June 14, 2006 NOON | |||||||||||||||||||||||||||
Ishwar K. Puri, Ph.D.Mathematical Model for the Cancer Stem Cell HypothesisAddress: Virginia Tech, Department of Engineering Science and Mechanics Date: Wednesday June 14, 2006 VCOM Host: Dr. Hara Misra |
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Background:Professor Ishwar K. Puri has served as Professor and Department Head of Engineering Science and Mechanics at Virginia Tech since 2004. He obtained his Ph.D. (1987), and M.S. (1984) degrees in Engineering Science (Applied Mechanics) from the University of California, San Diego after obtaining a B.Sc. (1982) in Mechanical Engineering from the University of Delhi. He served as an Assistant Research Engineer at the University of California, San Diego from 1987-90. He was appointed as an Assistant Professor in the Mechanical Engineering Department at the University of Illinois at Chicago in 1990, was promoted to the rank of Associate Professor with tenure in 1994, and to the rank of Professor in 1999. He served as Director of Graduate of the Mechanical and Industrial Engineering programs from 1994-97, and 1999-2000. He served as Associate Dean for Research and Graduate Studies (2000-01), and as Executive Associate Dean of Engineering (2001-04). He served on the steering committee of the UIC Institute for Environmental Studies and headed UIC's micro- and nanotechnology initiatives. Professor Puri is a Fellow of the American Society of Mechanical Engineers (ASME) and of the American Association for the Advancement of Science (AAAS). He was a Distinguished Guest of the Swiss Leonard Euler Center of the European Research Community of Fluid Turbulence and Combustion in 1998 and 1999. He was a 1993 American Association for the Advancement of Science-Environmental Protection Agency (AAAS-EPA) Environmental Fellow, a 1992 NASA/Stanford University Center for Turbulence Research Fellow, and a 1991 Visiting Fellow at the University of Cambridge. He has served as a program and peer review panelist for the Department of Energy, US EPA, and NSF. He is an editor of the journal Experimental Heat Transfer. Professor Puri has conducted research through major grants from NASA, NSF, DOE, US EPA, State of Illinois, and industry. He established a European-US consortium to conduct engineering student exchanges at the undergraduate and graduate levels that was funded through the US Department of Education FIPSE program. His students are placed in major corporations and at universities worldwide. He is the author of over 200 archival and conference publications in the fields of combustion, transport phenomena, and computational science and engineering (e.g., related to emissions, self assembly, magnetic fluids, drug targeting, cell mechanics, nanoscale fluid dynamics, and hydrogen storage). He has edited a book on the environmental implications of combustion processes, a textbook on advanced thermodynamics engineering and another on combustion science and engineering. Summary:Stem cells for malignant tumor growth. Various genes that regulate self-renewal in normal stem cells are also found in cancer stem cells. This implies that cancers can occur due to mutations in normal stem cells and early progenitor cells. A predictive mathematical model that is based on the cell compartment method will be presented to pose and validate nonintuitive scenarios proposed through the neural cancer stem cell hypothesis. The growths of abnormal (stem and early progenitor) cells from their normal counterparts will be ascribed with separate mutation probabilities. Stem cell mutations are found to be more significant for the development of cancer than a similar mutation in the early progenitor cells. The model also predicts that, as previously hypothesized, repeated insult to mature cells increases the formation of abnormal progeny, and hence the risk of cancer. Suggested reading:
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| Monday, May 8, 2006 NOON | |||||||||||||||||||||||||||
Stephen Gregory Guill, MS
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Background:Stephen Guill is a Ph.D. candidate at Virginia Tech in the department of Human Nutrition, Foods, and Exercise, with a specialization in Clinical Exercise Physiology. Stephen has also completed doctoral certificates in Gerontology and Molecular Cell Biology and Biotechnology. For the past 6 years, Stephen has supervised laboratory testing and program activities for chronic disease rehabilitation programs at Wake Forest University, where he received his M.S degree in Health and Exercise Science in 2003, and Virginia Tech. Stephen??s current research examines the relationship between obstructive sleep apnea and chronic disease, with an emphasis in metabolic syndrome and diabetes. Summary:Obstructive sleep apnea (OSA) is an obesity-related condition characterized by repetitive upper airway collapse during sleep. At least 1 in 5 adults may be affected. In addition to excessive daytime sleepiness and impaired cognitive function, individuals with OSA are at greater risk for hypertension and diabetes. This seminar will describe key features of OSA pathology, clinical presentation, and treatment options. Hypothesized mechanistic links between OSA and chronic disease will be explored, including the role of the sympathetic nervous system, intermittent hypoxia and hypercapnia, and fragmented sleep. Finally, recent OSA research conducted at Virginia Tech will be presented, with an emphasis on initiatives for future research. |
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| Monday, May 1, 2006 NOON | |||||||||||||||||||||||||||
Darwin Jorgensen, Ph.D.
Title: "We all work the same way: studies on cardiovascular and respiratory function in certain marine crustaceans"
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Research:Dr. Darwin D. Jorgensen has been the Brian H. Thornhill Professor and Chair, Biology Department, Roanoke College since 2003. His research areas include: comparative animal physiology, cardiovascular and respiratory physiology, invertebrate biology, the history and rhetoric of science. Recent and Selected Professional Publications:
Summary:My students and I have been studying cardiovascular and respiratory physiology of blue crabs and lobsters. Extremely important to the fisheries industry along the east coast of the U.S. (including our Chesapeake Bay), they are interesting physiological models of how water-breathing animals work. Both species are migratory, walking (and/or swimming) underwater for considerable distances. I will provide an overview of how they work (drawing comparisons to the mammalian situation) and discuss some of our past, current, and future projects. |
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| Thursday March 23, 2006 NOON | |||||||||||||||||||||||||||
Kumar MallikarjunanTitle: Sniffing out the Discomfort Mailing Address: 312 Seitz Hall, Virginia Tech Date: Thursday March 23, 2006 VCOM Host: Dr. Hara Misra |
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Research:Dr. Mallikarjunan, specialized in food engineering, has extensive experience with the development of non-destructive non-contact sensing technologies such as electronic nose and ultrasound for quality evaluation in food products. He also worked in the area of food safety and in prevention of pathogen contamination and treatment of pathogen contaminated food products through thermal and non-thremal processing technologies. He would like to extend his research into biomedical applications and seek collaborative support from VCOM. Summary:Electronic nose technology, which mimics a biological nose, can overcome some of the difficulties associated with classical odor measurement, and electronic noses have many applications in biomedical industry. They are recently gaining momentum with respect to a variety of applications for diagnostics, routine analysis, prescreening and microbial enumeration. With all the possibilities, still the technology is being pushed by the system manufacturers than pulled by need from the industry. Biomedical industry is very skeptical about the capabilities of the systems, and this presentation will provide an overview of available technologies, systems, applications, and implementation issues. Focus will be given to the pitfalls with these techniques compared to existing analytical methods for odor measurement. Both desktop and handheld-type systems and systems for on-line monitoring will be discussed. Issues like cost, training, sensor drift, statistical limitations, and sampling limitations will be analyzed and future directions for research and development will be discussed. Dr. Mallikarjunan will also discuss the potential for future research collaborations with VCOM faculty. |
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| Tuesday January 10, 2006 | |||||||||||||||||||||||||||
Dongmin Liu, MS Ph.D. Title: Genistein and pancreatic beta-cell function Email: doliu@vt.edu Date: Tuesday January 10, 2006 VCOM Host: Dr. Hara Misra |
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Dr. Dongmin Liu received his MS in animal quantitative genetics in China, in 1992. He later obtained his Ph.D in animal nutritional physiology at Virginia Tech in 2000. His Postdoctoral research was in Endocrinology and vascular biologyat the Department of Internal Medicine in the University of Iowa Medical College between 2000-2003.
Research:Dr. Liu discovered a DHEA (a human steroid) receptor in vascular endothelial cells in 2002; received a postdoctoral research award from the University of Iowa Medical College and a postdoctoral fellowship award from the American Heart Association. Started a molecular nutrition position as an assistant professor in the Human Nutrition, Foods and Exercise at Virginia Tech in 2004. Current research in the lab is focusing on to investigate how soy isoflavones modulate vascular and pancreatic beta-cell function, and how DHEA regulates angiogenesis and vascular endothelial apoptosis. Summary:Although genistein, a soy isoflavone, has beneficial effects on various tissues. It is unclear whether it plays a role in pancreatic beta-cell function. Here we present evidence that genistein increases rapid glucose-stimulated insulin secretion (GSIS) in both insulin secreting cell lines (INS-1 and MIN6) and pancreatic islets of mice and humans. The effect of genistein on GSIS was not dependent on its known effect such as binding to estrogen receptor (ER) or inhibition of protein tyrosine kinase (PTK). Consistent with its effect on GSIS, genistein increases intracellular cAMP and activates protein kinase A (PKA) in both cell lines and the islets by a mechanism that does not involve ER or PTK. The induced cAMP by genistein, at physiological concentrations, may result primarily from enhanced adenylate cyclase activity. Pharmacological or molecular intervention of PKA activation indicated that the insulinotropic effect of genistein is primarily mediated through PKA. In addition, we found that genistein also activates the CRE-regulated gene expression in beta-cells. Furthermore, genistein activates extracellular signal-regulated kinase 1/2 in clonal beta-cells and stimulates the cellular proliferation of beta-cells and pancreatic islets. These findings demonstrated that genistein acts directly on pancreatic beta-cells, leading to activation of the cAMP/PKA signaling cascade to exert an insulinotropic and proliferative effect, thereby providing a novel role of soy isoflavones in the regulation of beta-cell function. |
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