Faculty Focus - John Olschowka

John A. Olschowka, Ph.D. Associate Professor: Neurobiology & Anatomy Department

Nearly an entire continent away from Rochester, NY, John Olschowka was born and raised in a small farming community in the fertile Sacramento Valley in northern California. His father was a farmer who grew peaches, plums, and walnuts and his mother was a college mathematics professor. These professions were reflected in their two children; with John following an academic research path while his brother pursued horticulture and mechanics.

John has come to exemplify the model profile of researcher, teacher, mentor, and colleague at the University of Rochester. Over the past twenty-two years John has emerged as a leader in the growing field of neuroinflammation and as a valued educator who trains medical students, graduate students, and undergraduates in both clinical and research disciplines. John garners approximately 200 contact hours each year teaching in the Human Structure and Function course. He has been consistently honored for his contributions to medical education, receiving commendations for excellence in medical education for the past four years in a row. John holds NIH R01 funding for his laboratory to examine inflammatory processes that accompany targeted gene therapy treatments for central nervous system diseases. He is also a co-investigator on 5 other NIH funded research projects that examine neuroinflammatory processes associated with diseases or acute injuries that affect the CNS. Currently an Associate Professor in the Department of Neurobiology and Anatomy, John has served on numerous departmental and university committees which in turn have helped to shape the academic climate and mission of the University of Rochester School of Medicine and Dentistry.

John obtained both his undergraduate and graduate degrees from the University of California Davis campus. As an undergraduate, John majored in Zoology and took classes which fostered his growing interest in anatomy. In his senior year, he completed an undergraduate Senior honors research project with the professor who had taught in his human gross anatomy course, Vijaya Vijayan (now Vijaya Kumari, Assistant Dean of Medical Education at UC Davis). He continued as the first graduate student in her lab, the only lab in that department doing neuroscience research at that time, earning his MS and then PhD in human anatomy. John's thesis work focused upon the development of the cerebellum.

In 1978, John accepted a postdoctoral fellowship at Johns Hopkins University in the Department of Cell Biology and Anatomy working with Mark Molliver. At the time that John began his postdoctoral work, immunocytochemistry was a relatively new technique. Having done a considerable amount of electron microscopy and histochemistry for his thesis work, John honed these skills developing novel immunocytochemical techniques to be used for electron microscopic examination. His postdoctoral mentor was mired at that time in the controversy over whether central catecholaminergic terminals formed synapses. In the periphery, catecholaminergic terminals don't really form true synapses but instead release transmitters diffusely. If this hypothesis were true in the central nervous system, neurotransmitter released from these terminals would affect large areas of the brain. John's work in the cortex instead proved that the catecholaminergic terminals formed synapses much like other axons in the nervous system.

From 1981-1983 John further diversified his training at the NIH as a staff fellow under the mentorship of Dave Jacobowicz, whose work focused upon catecholamine pharmacology, histology and biochemistry. The Jacobowicz lab worked closely with Julius Axelrod, a recipient of the Nobel prize for his work defining the catecholamine pathways. At this time, peptide neurotransmitters had recently been identified and many NIH researchers were focused upon identifying new neuropeptides, developing antibodies to them, and then mapping their distributions. Within this competitive environment of the NIH, John mapped two novel neuropeptides, bovine pancreatic polypeptide (now known as NPY) and corticotrophin releasing factor (CRF). Recognizing the importance of understanding the functioning of the system within their defined distributions and pathways, John began to pursue questions related to regulation of individual neuropeptide systems. It was this work that prompted John Sladek to recruit John Olschowka to the University of Rochester.

At the time of his arrival at the U of R, John was working on the regulation of CRF production and release within the paraventricular nucleus and CRF neurons. In order to address these questions, he used double and triple immunohistochemical labeling methods at the EM level. About the time he was beginning his work here at the U of R, two papers were published that dramatically shifted the directions of his research. It turns out that the conclusions of these two pivotal papers in Immune-Nervous system interactions were actually incorrect, but their content has had great impact upon an entire field of research and upon John's own research directions and career.

The first paper, published in Science, reported that in humans interleukin-1-containing neurons synapsed on CRF neurons in order to regulate the hypophyseal-adrenal axis. There was evidence that with inflammation, the hypophyseal-adrenal axis was turned on triggering eventual glucocorticoid secretion from the adrenals. The second paper was a study of IL-1 in rats in which an antibody had been used to localize IL-1 in neurons. In trying to replicate this work in the rat, John tried every commercially-available antibody without success. In a further effort to replicate their data, John called the author of the rat IL-1 paper to ask him for some of the antibody that had been used to localize IL-1 in neurons. The author of the second paper replied that they had not been able to replicate the data either. Concluding that he couldn't look directly at the protein, John decided to learn some molecular biology techniques that would allow him to step back one level and look at the RNA levels instead. He learned PCR and in situ hybridization techniques which have shaped the directions of his research.

Over the two decades since that time, John has continued to explore the functions of immune related molecules in the brain, both in healthy and pathological states. John has examined differences between how the brain responds to injury in young versus older individuals. Pointing out that the immune response is partially activated as a natural part of the aging process, John notes further that this process is poorly understood. To address this, his lab has recently been developing models for examining this process in both young and old individuals.

In young individuals, microglial cells are activated for 2-3 days following injury and then become quiescent. Long term detrimental effects become manifest in the susceptible cells; the neurons, the oligodendrocytes and their precursor cells (neuroprogenitors or glial progenitors). In contrast, injury of the aged brain leads to prolonged glial activation and inflamination. Suppression of glial or neuroprogenitors by inflammatory molecules appears to occur in the young and old alike. In collaboration with Kerry O'Banion, John is examining the role of a Cox-2 inhibitor in the process of fostering neurogenesis during the inflammatory process.

Along with Howard Federoff and Bill Bowers, John is also examining the inflammatory processes that accompany gene therapy and is investigating how to selectively activate or inhibit these processes. Since just about any CNS injury causes inflammatory reactions that attract cells from the bloodstream, gene therapy agents could theoretically be administered intravenously. This provides a potential mechanism by which to target therapeutic genes directed specifically to the sites of injury without making targeted injections into brain tissue. People have been trying to target delivery of genes to the CNS (e.g. growth factors for treatment of Parkinson's disease or Amyotrophyic Lateral Sclerosis. If, in each of these diseases, a stereotyped pattern of localized inflammation is present, John and his colleagues could use this inflammatory response to target gene therapy directly to the affected site. With his colleagues Stephanos Kyrkanides and Kerry O'Banion, John is investigating inflammatory processes that accompany Tay Sachs and Sandoff's diseases in an attempt to identify potential gene therapies.

Although several drugs can be used to inhibit inflammatory responses in the peripheral nervous system, many of these agents are not effective at the central nervous system level since they fail to cross the blood brain barrier. The process of examining inflammatory responses in the brain is complicated by the fact that it is difficult to sort out the role of infiltrating immune cells (macrophages) from the role of the resident immune cells, the microglia. In order to effectively quell CNS inflammation, both pathways would need to be inhibited. In conjunction with this work, John has been examining the inflammatory consequences of radiation exposure and evaluating potential therapies to reduce inflammatory responses with his collaborators in Radiation Oncology, Paul Okunieff, Jackie Williams, and Jack Finkelstein.

John has been very active in his service to the mission of the university, training scientists and physicians. An instructor of gross anatomy for 22 years, John teaches in the Human Structure and Function course, the third version of the gross anatomy curriculum since he's been here. He enjoys teaching anatomy because of the level of contact between the instructor and students. Much of the teaching goes on in the laboratory, not in a lecture hall so there are ample opportunities to get to know the students and interact with them in smaller groups. John also co-directs and teaches in the new graduate Neuroinflammation course offered for the first time in Spring 2004. In the past six years alone, 23 undergraduates have done research in his lab. To date, John has trained 63 graduate students, 4 medical students, and 8 postdoctoral fellows in a variety of research methods including molecular biology, in situ hybridization, EM and light microscopic immunohistochemistry, EM and light microscopic image analysis. Of these, 19 students have completed all or part of their PhD thesis work in his laboratory. Having served on the thesis committees of 48 former students, John presently serves on 10 thesis committees for students in the departments of Neurobiology & Anatomy, Neuroscience, Pharmacology & Physiology, Toxicology, and Immunology. For several years, John served as the head of the Neuroscience Cluster in the Interdepartmental Graduate Program in Neuroscience (IGPN) and chair of the IGPN admissions committee and is currently the director of the graduate program in Neurobiology & Anatomy.

John resides in Pittsford with his wife, Pattie, a clinical trial coordinator in the University of Rochester Department of Urology. They have two children. Their daughter, Malllory, is a student at the University of Rochester and teaches dance. Their son, Tristan, is developing his career as a professional musician as well as studying music recording. In his free time, John enjoys watching lacrosse, a passion that emerged during his postdoctoral years at Johns Hopkins. Although John doesn't ski, he enjoys spending some down time at the lodge while his children hit the slopes.

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