U NERVECENTER H. Fishbeck, MD, were and continue to be critical mentors for Paulson. Both have made seminal contributions to our understanding of brain diseases. Paulson praised them as “phenomenally good scientists with a nose for biological problems, while never losing sight of the patient.” For 10 years at the University of Iowa, Paulson focused on hereditary ataxias and polyglutamine diseases; in 1997, his lab described the abnormal protein aggregates in polyglutamine diseases, which are now recognized as a pathological hallmark in these inherited diseases. Since moving to the University of Michigan, where he oversees the neurodegenerative disease research programs and directs the Michigan Alzheimer Disease Center, he has continued with basic and translational studies to understand the mechanisms of neurodegenerative disease and develop therapeutic strategies to treat them. He is now codirector of a newly established Center for Protein Folding Diseases at Michigan. Enamored with the biology of behavior, Bar-Or took a double major in biology and psychology as an undergraduate. During his medical school neurology rotation at McGill, he encountered Professors Michael
Rasminsky, MD, PhD, and Jack P. Antel, MD. “I was most impressed,” he says, “with the way they distilled complex clinical problems into their elements and, based on careful listening and observing, reconstructing what the problem was likely to be. To them I owe the excitement and passion of going into neurology.” His interest in multiple sclerosis (MS), now a major focus of his research lab at McGill, was fed during neurology residency training and subsequently neuroimmunology fellowship at Harvard, initially by Peter N. Riskind, MD, PhD, and then subsequently by David A. Hafler, MD. “Academically, I realized that this field represented an exciting interface of fast-paced neuroscience and immunology,” recalls BarOr of those years. In addition, there was, for him, the “compelling clinical aspect of an illness that was only partially treatable and that afflicted relatively young people throughout their most productive years, substantially impacting family, work, and society.” The convergence of scientific intrigue with the opportunity for developing novel and meaningful therapeutic targets “was something I found very attractive,” he says. MS continues to be a focus in the cellular
Considering a Career in Neurology Research? Heed These Words Frances E. Jensen, MD: “There are huge opportunities in early phase clinical trials and clinical investigation; at the same time, we also recognize that the master clinician has a very important role to play in the process of translating and integrating discoveries in genomics and the basic sciences. What we don’t want to do is over-silo ourselves. The same synaptic or inflammatory proteins are affected, to different degrees, and different times, in a variety of neurological disease, from MS to stroke to epilepsy to dementia.” Henry L. Paulson, MD, PhD: “This is exactly the right time for someone to go into neurology, because the ability to be a major contributor in helping find therapies for largely untreatable diseases is high. But you must be excited and intrigued by what you work on: if your passion is within the realm of neuroscience, then the opportunities are virtually limitless.” Amit Bar-Or, MD, FRCP(C): “As individual fields are increasingly complex, both the beauty and imperative of multidisciplinarity become more apparent. I encourage people who intend to subspecialize, for example as dedicated clinical trialists or as a basic science investigators, to nonetheless strive to at least become familiar with the language of complementary areas of expertise.” DOI: 10.1002/ana.24008
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and molecular immunology lab that Bar-Or directs. MS is one condition for which animal models have yet to capture all aspects of the human disease pathophysiology. Given this, Bar-Or established an Experimental Therapeutics Program, which develops and applies biological assays in the context of clinical trials to better understand disease mechanisms. “This paradigm has been very rewarding,” he says, “because whether or not the therapy is successful in meeting a desired clinical endpoint, much can be learned about the illness itself through thoughtful incorporation of biological measures. These are important lessons our patients can teach us that we will never be able to learn in any in vitro or animal model system.”
Future Wide Open Bar-Or notes that, despite recent advances in the field of MS, important unmet needs remain. However, he points to several opportunities, including collaborations that cut across different disciplines. For example, “several classic neurodegenerative diseases—such as Alzheimer, Parkinson, and [amyotrophic lateral sclerosis]—have had a resurgence of interest in inflammatory mechanisms of disease. Coordinated studies will allow us to learn a great deal about one condition through insights gained from another,” he says. Jensen points to collaboratives such as One Mind and the NIH’s BRAIN Initiative as evidence that this is “a transforming time for neurology. There is a surge of basic science investigating synaptic plasticity, neural function, and signaling pathways, and at the same time we have the computational wherewithal to accelerate our discoveries.” Paulson, describing himself as “an eternal optimist,” agrees that the future of academic neurology is bright. “We have all these tools available that allow us to query how the brain works in normal and disease states; President Obama and NIH Director Francis Collins have identified the importance of understanding brain function and dysfunction as a key initiative. At the same time that our understanding has grown, the identification of effective therapies has lagged. That’s why we need new minds to push the agenda forward.” GRETCHEN HENKEL DOI: 10.1002/ana.24007
Volume 74, No. 3
Rasminsky, MD, PhD, and Jack P. Antel, MD. “I was most impressed,” he says, “with the way they distilled complex clinical problems into their elements and, based on careful listening and observing, reconstructing what the problem was likely to be. To them I owe the excitement and passion of going into neurology.” His interest in multiple sclerosis (MS), now a major focus of his research lab at McGill, was fed during neurology residency training and subsequently neuroimmunology fellowship at Harvard, initially by Peter N. Riskind, MD, PhD, and then subsequently by David A. Hafler, MD. “Academically, I realized that this field represented an exciting interface of fast-paced neuroscience and immunology,” recalls BarOr of those years. In addition, there was, for him, the “compelling clinical aspect of an illness that was only partially treatable and that afflicted relatively young people throughout their most productive years, substantially impacting family, work, and society.” The convergence of scientific intrigue with the opportunity for developing novel and meaningful therapeutic targets “was something I found very attractive,” he says. MS continues to be a focus in the cellular
Considering a Career in Neurology Research? Heed These Words Frances E. Jensen, MD: “There are huge opportunities in early phase clinical trials and clinical investigation; at the same time, we also recognize that the master clinician has a very important role to play in the process of translating and integrating discoveries in genomics and the basic sciences. What we don’t want to do is over-silo ourselves. The same synaptic or inflammatory proteins are affected, to different degrees, and different times, in a variety of neurological disease, from MS to stroke to epilepsy to dementia.” Henry L. Paulson, MD, PhD: “This is exactly the right time for someone to go into neurology, because the ability to be a major contributor in helping find therapies for largely untreatable diseases is high. But you must be excited and intrigued by what you work on: if your passion is within the realm of neuroscience, then the opportunities are virtually limitless.” Amit Bar-Or, MD, FRCP(C): “As individual fields are increasingly complex, both the beauty and imperative of multidisciplinarity become more apparent. I encourage people who intend to subspecialize, for example as dedicated clinical trialists or as a basic science investigators, to nonetheless strive to at least become familiar with the language of complementary areas of expertise.” DOI: 10.1002/ana.24008
A12
and molecular immunology lab that Bar-Or directs. MS is one condition for which animal models have yet to capture all aspects of the human disease pathophysiology. Given this, Bar-Or established an Experimental Therapeutics Program, which develops and applies biological assays in the context of clinical trials to better understand disease mechanisms. “This paradigm has been very rewarding,” he says, “because whether or not the therapy is successful in meeting a desired clinical endpoint, much can be learned about the illness itself through thoughtful incorporation of biological measures. These are important lessons our patients can teach us that we will never be able to learn in any in vitro or animal model system.”
Future Wide Open Bar-Or notes that, despite recent advances in the field of MS, important unmet needs remain. However, he points to several opportunities, including collaborations that cut across different disciplines. For example, “several classic neurodegenerative diseases—such as Alzheimer, Parkinson, and [amyotrophic lateral sclerosis]—have had a resurgence of interest in inflammatory mechanisms of disease. Coordinated studies will allow us to learn a great deal about one condition through insights gained from another,” he says. Jensen points to collaboratives such as One Mind and the NIH’s BRAIN Initiative as evidence that this is “a transforming time for neurology. There is a surge of basic science investigating synaptic plasticity, neural function, and signaling pathways, and at the same time we have the computational wherewithal to accelerate our discoveries.” Paulson, describing himself as “an eternal optimist,” agrees that the future of academic neurology is bright. “We have all these tools available that allow us to query how the brain works in normal and disease states; President Obama and NIH Director Francis Collins have identified the importance of understanding brain function and dysfunction as a key initiative. At the same time that our understanding has grown, the identification of effective therapies has lagged. That’s why we need new minds to push the agenda forward.” GRETCHEN HENKEL DOI: 10.1002/ana.24007
Volume 74, No. 3
