Dr. Amy Brooks-Kayal is a global leader in epilepsy research, with seminal contributions to our understanding of the cellular and molecular pathways that mediate the development of epilepsy following brain injury, with particular emphasis on GABAergic signaling and its regulation. Dr. Amy Brooks-Kayal embodies the seamless blending of individual research contributions and extraordinary contributions to research via guidance and mentoring of junior individuals as well as via influencing the policy and research directions of whole institutions.
She grew up in Florida and moved to Cornell for undergraduate studies and to enjoy snowy weather. She met her husband, Rana, at Cornell, and they are proud parents of two grown children Anjali and Zach, that keep her flying all over the world for adventures. Balancing work and family has always been a priority. She is a wine collector with a large cellar and a keen interest in keeping the table supplied with a pairing of good food and great wine.
Professionally, Dr. Brooks-Kayal has worked to develop novel therapeutic approaches to the prevention and treatment of both seizures and cognitive co-morbidities associated with epilepsy. She pioneered the development of pediatric rodent epilepsy models. These are now well established, but at the time there was controversy around the mild injury and limited or even absent cell loss that occurs in young animals following an episode of status epilepticus. The widespread acceptance that age dramatically alters epilepsy and epileptogenesis is in large part due to the work of Dr. Brooks-Kayal. The Brooks-Kayal lab, as well as several other labs, have demonstrated that immature animals develop epilepsy without cell loss and with minimal to no neuronal sprouting, highlighting the distinct importance of incorporating development into the study of epilepsy. Her lab has been the major proponent of the role of GABA subunit switch in the development of epilepsy and the distinct difference in GABA subunit expression depending on the age of the animal at the time of epileptogenic insult.
Dr Brooks-Kayal has made three seminal discoveries: 1. Changes in GABAergic neurotransmission following epileptogenic brain injuries. Her laboratory first reported changes in GABA receptor subunits occurring within single dentate granule neurons in the hippocampus, specifically a reduction in α1 and increase in a4 subunits that correlated with changes in GABA receptor function including reduced Type I benzodiazepine sensitivity and increased sensitivity to zinc inhibition that would be predicted to reduce the effectiveness of inhibition during times of repetitive stimulation such as occurs at seizure onset. These findings suggest that as occurs during development, the GABAergic system is highly plastic following brain injuries and in chronic epilepsy, and that these changes vary by cell type and subregion of the hippocampus. With respect to scholarly activities, Dr. Brooks-Kayal has authored a large number of original research articles as well as review papers. She has some of the most cited publications (Hsu et al., PNAS 2003; Raol et al., Ann. Neurol. 2003; Brooks-Kayal et al., Nat. Med. 1998) in the field of GABA receptors and epilepsy. 2. Regulation of GABA receptor expression changes after epileptogenic brain injuries. Her research in this area focused on the mechanisms regulating GABA receptor subunit expression and uncovered a role of BDNF in regulating seizure- induced regulation of GABAA receptor α4 and α1 subunits via the JAK/STAT pathway. Furthermore, her lab showed that blockade of this pathway with a JAK/STAT inhibitor could reverse BDNF-induced Gabra1 downregulation in cultured hippocampal neurons and most importantly in the dentate gyrus following pilocarpine- induced SE in rats in vivo. Towards this goal she published a seminal paper in Science Signaling (Lund et al., Sci. Signaling 2008) demonstrating the role of BDNF in regulation of GABAA receptor transcriptional activation via the JAK/STAT pathway. 3. Development of disease modifying and preventative therapies for epilepsy. Her lab demonstrated that preventing the reduction in GABAA receptor subunit α1 expression after SE via viral-mediated transfer of an a1 subunit transgene in adult rodents reduced subsequent epilepsy development (Raol et al., J. Neurosci. 2006). These studies highlight the importance of a1 subunit downregulation as a critical mechanism contributing to development of acquired epilepsy. Her recent efforts have been focused on molecular dissection of the signaling pathway controlling the α1 subunit so that its expression can be therapeutically targeted. Towards this goal, her lab showed more recently that inhibition of the JAK/STAT pathway was disease modifying in adult rodent models of acquired epilepsy. They have identified a brain permeable STAT3 inhibitor, WP1066, that when administered systemically at the time of SE results in partial and transient inhibition of STAT3 phosphorylation in hippocampus in the rat pilocarpine model. Her discoveries are ripe for translation in human epilepsies.
The contribution of Dr. Brooks-Kayal to Neuroscience research extends far beyond her own work and is transforming the field in the present- and the future through her leadership mentoring and scholarly activities:
Dr. Brooks-Kayal is currently Professor and Chair of the Department of Neurology at the University of California Davis. In her prior role as Chief of Pediatric Neurology at the University of Colorado, She established a division that grew to be a top 10 program nationally both in clinical care and research. Over the past 20 years, she has served as a mentor for numerous graduate students, post-doctoral trainees, and junior faculty in Pediatric Neurology and Neuroscience at the University of Pennsylvania, the University of Colorado and now, at Davis. Many have gone on to have successful independent careers in academic research.
The success of research with high relevance to child neurology demands that institutions at national and international levels recognize the vital importance of this research and provide appropriate funding and funding opportunities. Dr. Brooks-Kayal has championed this cause for two decades, with stunning commitment, aplomb- and effectiveness.
Commencing with her specialty, Epilepsy, Dr. Brooks-Kayal literally transformed the American Epilepsy Society. As Vice-president then President (2012-15), she revamped the management structure, which allowed funneling of millions of dollars to research rather than management companies. She led a 5-year strategic plan which prominently recognizes developmental epilepsies, and increased research funding provided to trainees and junior investigators by ~3 fold.
Dr. Brooks-Kayal, acting as member of the Scientific Advisory Board of Citizens United for Curing Epilepsy (CURE): was instrumental in guiding the research direction of the foundation, resulting in many millions of dollars directed towards early-career awards (e.g., ‘taking flight’) for pediatric neuroscience. Dr. Brooks-Kayal embarked on a major set of transformative contributions to child neurology-relevant research through her efforts with NIH/NINDS: First, she led two benchmark Conferences (2007 and 2013) where she highlighted the importance of Cognitive and Psychological Co-Morbidities of Epilepsy and the serious gap in the study of these problems. Second, she actively participated in the Program Review Panel of the NINDS Antiepileptic Drug Discovery (ADD) Program, that had traditionally ignored neonatal and childhood seizures and epilepsies. Here two Review Panels (2012 and 2015) resulted in major changes in the direction of the program. Dr. Brooks-Kayal is now continuing her national guidance role as member of the External Advisory Board (2015-2019) of the NINDS Epilepsy Therapy Screening Program (ETSP). Again, she is providing guidance and oversight of implementation of changes in program direction.
The most powerful way to influence policy and emphasize changes at the national / NIH levels is via service on the individual institutions’ Council. This is a rare honor, and members work with Institute Directors and colleagues to influence research priorities. Dr. Brooks-Kayal is a rare Child Neurologist on the NINDS Council (2014-18). As such, she has advised NINDS Directors and the Institute on policy and procedures affecting the extramural research programs and provides a second level of review for grant and cooperative agreement applications considered by the Institute for funding.
In summary, Dr Brooks-Kayal is an internationally recognized leader in research with strong relevance to child neurology. She is a passionate and gifted educator and mentor at individual, institutional and national levels. Uniquely, she is also contributing to developmental neuroscience research through her vision of enabling the resources mandatory for this research via leadership at societies, foundations and the NIH.