T Cells at the Interface of Immune-CNS Cross-Talk

Speakers

Organizers

Joshua F. Apgar, PhD

Boehringer Ingelheim Pharmaceuticals

Josh Apgar is a Principal Scientist in the Systems Biology Group of the Department of Immunology and Inflammation at Boehringer Ingelheim Pharmaceuticals. His work leverages physics based models to: translate in vitro and in vivo data, assess target feasibility, understand drug mechanism of action, and predict human doses. The ultimate goal of this work is to reduce late stage attrition in drug development through a deep and quantitative interrogation of drug pharmacology and disease pathophysiology. Josh received his PhD from MIT in Biological Engineering where he worked on experiment design for Systems Biology, focusing on the identification of tractable experiments that could allow for the estimation of unknown parameters and reveal complex mechanisms in signal transduction networks.

Henry Kao, PhD

Lundbeck Research USA

Henry Kao received his PhD in Immunology at the University of Pittsburgh in the laboratory of Olivera Finn, where he created a T cell-based antigen discovery system that led to the identification of Cyclin B1 as a novel epithelial tumor antigen. This was followed with post-doctoral work at Washington University with Paul Allen, where he studied the role of the CD4 co-receptor in T cell development and its molecular movement at the immunological synapse. Henry then joined Allergan in 2008, where he setup a new immunology/protein biologics laboratory, and led in the development of ultrasensitive methods to measure large molecules in complex matrices. Since joining the Neuroinflammation Biology Unit at Lundbeck since 2010, Henry has focused on integrating his immunology expertise while working with fellow neuroscientists on devising new modalities to treat CNS disorders.

Anthony Slavin, PhD

Boehringer Ingelheim Pharmaceuticals

Anthony Slavin received his PhD from the University of Melbourne studying the then novel encephalitogenic properties of MOG. He subsequently completed post-doctoral studies at the Center for Neurologic Diseases in Boston before taking a position at Stanford University Division of Rheumatology. He left Stanford to join a start-up company, Tularik, which was eventually acquired by Amgen before moving to Novartis. Anthony is currently Director of Immunology and Inflammation at Boehringer Ingelheim.

Roland Staal, PhD

Lundbeck Research USA

Roland Staal received his PhD in Pharmacology from the University of Medicine and Dentistry of NJ with a focus on in-vivo models of dopaminergic neurodegeneration, including amphetamines and the Parkinsonian neurotoxin MPTP. He did his post-doctoral studies at Columbia University, where he studied the function of alpha-synuclein as well as its role in sensitizing mice to MPTP. He then joined Wyeth Research's department of neurodegeneration, studying protein mis-folding and potential therapeutic interventions including aggregation inhibitors and immunotherapies for both Parkinson's and Alzheimer's disease. He then joined Lundbeck Research, where he was instrumental in establishing the Neuroinflammation biology unit. The unit works with various technologies including flow cytometry, cell sorting, ELISAs and Cellomics to evaluate various markers and outcomes of Neuroinflammation in in-vivo models as well as cell lines and primary neuronal and microglial cultures. His current focus is on targeting neuroinflammatory aspects of CNS diseases.

Jennifer Henry, PhD

The New York Academy of Sciences

Speakers

Stanley H. Appel, MD

Methodist Neurological Institute

Stanley H. Appel, MD is the Director of the Methodist Neurological Institute, Chair of the Department of Neurology, and the Edwards Distinguished Endowed Chair for ALS at The Methodist Hospital in Houston, TX. He is also Professor of Neurology at Weill Cornell Medical College.

Dr. Appel is a native of Massachusetts and received his Bachelor Degree at Harvard University and his Medical Degree from Columbia College of Physicians and Surgeons. He was previously Chair of the Department of Neurology at Baylor College of Medicine as well as Chief of the Neurology Division and the James B. Duke Professor of Medicine at Duke University Medical Center. Dr. Appel has served on a number of MDA advisory committees since 1991. He was named MDA's Honorary Vice Presidents from 1989-2003, and has been serving on MDA's national Board of Directors since 2003. He is Director of the MDA/ALS Research and Clinical Center at the Methodist Neurological Institute.

Research in Dr. Appel's laboratory has focused on developing new insights into degenerative neurologic diseases with primary emphasis on ALS. His studies of mutant SOD transgenic mice have documented that neuroinflammation and activated microglia are neuroprotective during early stages of disease and cytotoxic during late stages of disease. These two stages appear to be modulated by peripheral T-cells that enter the CNS at sites of neuronal injury; Th2 and regulatory T-cells are increased in early stages and appear to provide neuroprotection, while Th1 T-cells are increased in later stages and mediate cytotoxicity. Comparable studies in human ALS have employed PCR techniques to confirm the presence of activated microglia and to demonstrate the presence of CD4 T-cells as well as immature and mature dendritic cells and enhanced chemokine signaling. His current studies are focused on determining how protective immunity with T-cells and microglia could prevent motor neuron injury and cell death.

Dr. Appel is a member of numerous professional societies and committees, and is the author of 15 published books and 390 articles on topics such as Amyotrophic Lateral Sclerosis (ALS), neuromuscular disease, Alzheimer Disease, and Parkinson Disease. He has received a number of awards for his accomplishments in Neurology and Biochemistry, including the 1997 Gold Medal for Excellence in Biomedical Research from Columbia College of Physicians and Surgeons, the 2003 Sheila Essey Award for ALS Research, 2004 MDA's Wings Over Wall Street Diamond Award, 2005 Texas Neurological Society Lifetime Achievement Award and the 2008 John P. McGovern Compleat Physician Award.

Britta Engelhardt, PhD

Universität Bern, Switzerland

Britta Engelhardt obtained a degree in Human Biology at the Medical School of the Philipps-University, Marburg in Germany in 1987. She performed her PhD thesis in the laboratory of Hartmut Wekerle (Max-Planck Clinical Research Group for Multiple Sclerosis, W¨rzburg and Max-Planck Institute for Psychiatry, Martinsried, Germany) and obtained a PhD in Human Biology (Dr.rer.physiol.) in January 1991. After a post-doctoral fellowship in the laboratory of Eugene C. Butcher at Stanford University, California, she set up her own research group at the Max-Planck Institute for Physiological and Clinical Research, Bad Nauheim, Germany in the department of Werner Risau (December 13th, 1998) in 1993. In 1998 she obtained the Venia Legendi for Immunology and Cell Biology from the Medical Faculty of the Philipps University Marburg, Germany. From 1999 to 2003 she headed her research group as a senior group leader at the same institute and the Max-Planck-Institute for Vascular Cell Biology, M¨nster, Germany. Since November 2003 Britta Engelhardt is Professor for Immunobiology at the University of Bern and the Director of the Theodor Kocher Institute. Dr Engelhardt is an expert in blood-brain barrier biology with a special focus on neuroinflammatory processes at the BBB. She has pioneered the use of intravital microscopy of the CNS white matter microcirculation allowing her to study leukocyte/BBB interaction in real time in live mice. For this work she has received the Herrmann-Rein Award of the Society for Microcirculation and Vascular Biology in 2001. She has published over 100 peer-reviewed papers in addition to reviews and book chapters on this topic. Britta Engelhardt currently coordinates the FP7 funded Collaborative Project JUSTBRAIN investigating options for paracellular drug delivery across the BBB. She is the current president of the Swiss Society for Microcirculation and Vascular Research (SSMVR). Additional activities of her include mentoring of talented students within the Schweizerische Studienstiftung and she is the current president of the Committee for Gender Equality of the Medical Faculty of the University of Bern.

Karl Frei, PhD

University Hospital Zurich, Switzerland

Born on April 28, 1950, in Zurich, Switzerland. He is married and has two daughters. He graduated from the Swiss Federal Institute of Technology (ETH) in Zurich, in 1983. He made one postdoctoral fellowship in the pharmaceutical industry (Ciba-Geigy Inc., Basel) and another in the field of neuroimmunology in the group of Adriano Fontana at the University Hospital Zurich. In the year 1994 he was promoted to professor in Experimental Medicine at the Faculty of Medicine, University of Zurich and in 1996 he became head of the Research Laboratory at the Department of Neurosurgery. His research interests lie in the field of brain tumors (therapy and interaction with the immune system) and on cellular and molecular aspects of the blood-brain barrier in various pathologies (tumor, epilepsy and bacterial meningitis). He is a highly cited researcher (ISI) in the field of immunology and has published 112 original articles and 7 reviews. He was co-laureat of the Hoechst-Marion-Roussel MS Research Award of the Swiss Multiple Sclerosis Society, in 1996. He is an ad hoc reviewer for more than 20 scientific journals and grant agencies and is a member of the Swiss Society for Immunology, Swiss Society of Molecular and Cellular Biosciences, Swiss Society for Neuroscience, and International Society of Neuroimmunology.

Howard E. Gendelman, MD

University of Nebraska Medical Center

Dr. Howard E. Gendelman is the Margaret R. Larson Professor of Internal Medicine and Infectious Diseases, Chairman of the Department of Pharmacology and Experimental Neuroscience, and Director of the Center for Neurodegenerative Disorders at the University of Nebraska Medical Center. Dr. Gendelman is credited in unraveling how functional alterations in brain immunity induce metabolic changes and ultimately lead to neural cell damage for a broad range of infectious, metabolic and neurodegenerative disorders. These discoveries have had broad implications in developmental therapeutics aimed at preventing, slowing or reversing neural maladies. His discoveries have led to novel immunopharmacology and nanomedicine strategies for Parkinson's and viral diseases currently being tested in early clinical trials. Dr. Gendelman obtained a Bachelor's degree in Natural Sciences and Russian Studies with honors from Muhlenberg College and his MD from the Pennsylvania State University-Hershey Medical Center where he was the 1999 Distinguished Alumnus. He completed a residency in Internal medicine at Montefiore Hospital, Albert Einstein College of Medicine and was a Clinical and Research Fellow in Neurology and Infectious Diseases at the Johns Hopkins University Medical Center. He is board certified in Internal Medicine. He occupied senior faculty and research positions at the Johns Hopkins Medical Institutions, the National Institute of Allergy and Infectious Diseases, the Uniformed Services University of the Health Sciences Center, the Walter Reed Army Institute of Research, and the Henry Jackson Foundation for the Advancement in Military Medicine before joining the University of Nebraska Medical Center faculty in March of 1993. He retired from the US Army with the rank of Lieutenant Colonel. Dr. Gendelman has authored over 400 peer-reviewed publications, edited nine books and monographs, holds eight patents, is the Editor-In-Chief and Founder of the Journal of Neuroimmune Pharmacology along with his service on eleven editorial boards, national and international scientific review and federal and state committees. He is the recipient of numerous local, national and international honors. Examples include the Henry L. Moses Award in Basic Sciences; the Carter-Wallace Fellow for Distinction in AIDS Research, Fellow/Member, the Infectious Diseases Society of American and the American College of Neuropsychopharmacology, the David T. Purtilo Distinguished Chair of Pathology and Microbiology, Pfizer Visiting Professorship in Infectious Diseases, the UNMC Scientist Laureate; NU Outstanding Research and Creativity and the Joseph Wybran Distinguished Scientist Awards. He received the Jacob Javits Research Award in the Neurosciences and the Career Research Award in Medicine from NINDS and UNMC, respectively. He is included amongst a selective scientific group listed on highly cited.com as one of the top cited scientists (0.5%, H-index of 72) in his field.

Christopher A. Hunter, PhD

University of Pennsylvania

Dr. Hunter has been focused for the last 20 years on understanding how the immune response to the parasite Toxoplasma gondii is regulated to allow the development of protective immunity as well as to limit T cell mediated pathology in the brain. This has involved the analysis of NK, T and B cells responses to infection and how cytokines, in particular IL-27, control these lymphocyte subsets. His laboratory has pursued the mechanisms used by IL-27 to influence the immune system and is relevant to many inflammatory processes in multiple experimental systems that include numerous infections as well as models of asthma, IBD and MS. In the last 5 years his laboratory has utilized different combinations of transgenic parasites and T cells to provide higher resolution analysis of individual parasite specific T cell populations. This in turn made it possible to apply multiphoton microscopy to image the innate and adaptive response to T. gondii in different tissues including the brain and to incorporate novel statistical approaches to describing lymphocyte behavior.

Michal Schwartz, PhD

Weizmann Institute of Science, Israel

Michal Schwartz is a professor of Neuroimmunology at The Weizmann Institute of Science, Rehovot Israel. She is married and the mother of four children. She received her BSc from the Hebrew University of Jerusalem, in Chemistry (Cum Laude), and her PhD in Chemical Immunology from the Weizmann Institute of Science (with honors). She spent two years as a postdoctoral fellow in the University of Michigan, Ann Arbor concentrating on CNS regeneration. Schwartz's research focuses on the role of innate and adaptive immunity in central nervous system (CNS) plasticity in health and disease. Schwartz was the pioneer in demonstrating that blood-derived macrophages are required for CNS repair (1998). She further demonstrated that blood-derived macrophages and activated resident microglia are not functionally redundant cells, but have distinct roles in the CNS repair process. The specific subset of monocyte-derived macrophages that exhibit suboptimal recruitment are those that locally display an anti-inflammatory function; these cells are needed for the resolution phase of healing, and were recently found by her team to be recruited to the injured site through the remote choroid plexus, which serves as a selective educative gate. Schwartz's team was also the pioneer in demonstrating the pivotal role of T lymphocytes in CNS repair. She proposed that the balance between effector and regulatory T cells determines the beneficial versus destructive effect of T cell activity on the brain. Schwartz formulated the concept of "protective autoimmunity," and demonstrated that CD4⁺T cells display a key role not only in repair, but also in maintaining life-long brain plasticity, including cognitive and mental activity, and neurogenesis from adult neural stem/progenitor cells, in health and disease. Her studies led to a paradigm shift in the perception of central issues in Neuroimmunology. By introducing the role of T cells in brain maintenance, Schwartz's studies suggested a new direction in understanding chronic neurodegenerative diseases (amyotrophic lateral sclerosis (ALS), Parkinson's disease, Alzheimer's disease, glaucoma, and others), mental disorders (depression and post-traumatic stress disorder (PTSD)), and brain senescence and dementia. Her publications include numerous peer-reviewed articles and invited reviews (approximately 270), many of which appeared in the highest ranked journals. Her publications are highly cited (H factor 72, based on Google Scholar). Professor Schwartz has been an invited lecturer at numerous meetings (approx 250), delivering keynote and presidential addresses, and is an elected member of the International and European Societies for Neuroimmunology. She received numerous awards in recognition of her contributions to the fields of optic nerve and spinal cord injury. In addition, Schwartz is a recipient of an ERC award, and is co-coordinator of an FP7 consortium for Neuroinflammation.

Lawrence Steinman, MD

Stanford University

Dr. Steinman is a Professor of Neurology and Neurological sciences and Pediatrics at Stanford University. He was the chair of the Stanford University Program in Immunology for a decade from 2001 to 2011. Dr. Steinman's research focuses on what provokes relapses and remissions in multiple sclerosis (MS) and in neuromyelitis optica (NMO), the nature of the molecules that serve as a brake on brain inflammation, and the quest for specific vaccines against MS and NMO. His work aims at describing mechanistic biomarkers to predict outcome to therapies in MS. He has developed two antigen specific therapies, using DNA vaccines, for MS and type 1 diabetes. He was senior author on the seminal 1992 Nature article that reported the key role of a particular integrin in brain inflammation. This research led to the development of the drug Tysabri, which is approved to treat patients with MS and Crohn's disease.

Dr. Steinman received his BA from Dartmouth College, Magna Cum Laude in Physics in 1968, and his MD from Harvard Medical School in 1973. He was a post-doctoral fellow in chemical immunology fellow at the Weizmann Institute of Science in Israel. Dr. Steinman returned to Stanford University Hospital as a resident in pediatric and adult neurology and then joined the faculty at Stanford in 1980.

Dr. Steinman has received numerous honors and awards, including the John M. Dystel Prize in 2004, from the American Academy of Neurology and the National MS Society for his research on MS. He has twice been awarded the Senator Jacob Javits Neuroscience Investigator Award by the Nation Institute of Neurological Diseases and Stroke. Steinman is a member of the Institute of Medicine of the National Academy of Sciences. In 2011 he received the Charcot Prize for Lifetime Achievement in MS research.

Dr. Steinman holds numerous patents in the areas of immunology, and for therapies of Huntington Disease and MS. He cofounded Neurocrine Biosciences, Bayhill Therapeutics, Cardinal Therapeutics, Atreca, and Transparency Life Sciences. He was a member of the Board of Directors of Centocor from 1988 until its sale to Johnson and Johnson in 1998.

Kevin J. Tracey, MD

Feinstein Institute of Medical Research

Kevin J. Tracey, is President and CEO of The Feinstein Institute for Medical Research, and Professor and President of the Elmezzi Graduate School of Molecular Medicine, in Manhasset, NY.  A neurosurgeon by training, his laboratory’s contributions to science include delineating the molecular and neurophysiological basis of neural circuits that control immunity. His publications include 240 papers, and The Institute for Scientific Information named him “Highly Cited Researcher in Immunology,” placing him in the top 0.5% of all publishing scientists.  Professor Tracey received his BS (Chemistry) from Boston College in 1979, and MD from Boston University in 1983. He trained as a neurosurgeon at the New York Hospital/Cornell University Medical Center, and was a guest investigator at the Rockefeller University. Since 1992, Tracey has directed his lab at the Feinstein Institute in Manhasset, NY, where in 2005 he was appointed President. Among Professor Tracey’s awards and honors are an Honorary degree from the Karolinska Institute, Stockholm, Sweden in 2009; an NIH Director’s Lecture; and membership in the American Society for Clinical Investigation, and the Association of American Physicians. Dr. Tracey is author of Fatal Sequence (Dana Press).