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Tallie Z. Baram, MD

Profile written by Robert S. Rust, MD

Tallie Z. Baram, MD

Tallie Baram was born and grew up in Tel-Aviv, Israel. Her pre-collegiate education was in Tel Aviv and at the English school in Addis-Ababa Ethiopia. She obtained a BSc (Biology) at Tel-Aviv University. Her doctorate in neuroendocrinology, supported by a Bloom Fellowship and a research grant of the European Molecular Biology Organization, was awarded with distinction by the Weizmann Institute of Science in 1978 upon the basis of a thesis concerning neural control and fate of gonadotropin releasing hormone. Dr. Baram’s academic distinction was marked by receipt of the highest award of the Weizmann Institute of Science. Her MD degree was granted two years later by studies at the university of Miami School of Medicine, supported by a Heim Weitzmann Postdoctoral fellowship. Dr. Baram’s career development, training in pediatrics and child neurology at Baylor, was particularly influenced by Marvin Fishman, Alan Percy, Rita Lee, and Ralph Feigin. Other mentors of note included O. Carter Snead, who played an important role in drawing her attention to epilepsy, Bob Snodgrass and Solomon Moshé, who contributed to the adaptation of her advanced neuroscientific skills to bench investigations pertinent to children with neurological diseases, and Wendy Mitchell and Shlomo Shinnar, who significantly enriched her training in clinical research. After completion of training her career path included two years at the university of Texas in Houston, and thirteen years at the university of Southern California. Since 1995 she has held the position of Professor of Pediatrics, Anatomy and Neurobiology and Neurology at the University of California, Irvine, where she also holds the Danette Shepard Chair of Neurological Sciences and is Director of the Epilepsy Research Center.

Dr. Baram has pursued a remarkable degree of extraordinarily productive concentration on many important and complex topics related to vulnerability to epilepsy in childhood, only a few of which can be characterized here. For example, the Baram laboratory has elegantly identified a major neurometabolic that protects the developing brain from excitatoxic cellular injury and associated epileptogenesis in the wake of cerebral energy failure. This study, cited more than 130 times, demonstrated that neonatal, as compared to mature brain, is enriched in mitochondrial uncoupling protein-2 (uCP-2) and that the degree of uCP-2 enrichment is a function of the degree to which diet is contains fat-rich maternal milk. The resilience that this imparts appears to be related to reduction in the accumulation of reactive oxygen species and inadequate calcium sequestration. Dr. Baram’s concern with the manner in which nature and nurture influence vulnerability has included the effect of handling of pups on genes that regulate hormonal and behavioral responses to stress. It was shown that this effect was associated with reduction in corticotropin releasing hormone (CRh), but increases in glucocorticoid receptor levels. The study design and results represent just one of many examples of how the Baram laboratory has meticulously demonstrated the manner in which a wide variety of experiences at particular developmental ages may result in what Dr. Baram has termed functional “hippocampal sculpting” – developmental changes that may improve or detract from function within a given context. The careful experimental design takes into consideration the important fact that the definition of the vulnerability of the developing brain to epilepsy is something of a developmentally determined “moving target.”

Particular attention has been devoted by Professor Baram to defining the vulnerability of developing brain to two forms of characteristically childhood- onset seizures: 1) febrile seizures and their relationship to the subsequent development of childhood- onset temporal lobe epilepsy, and 2) infantile spasms. The Baram laboratory was the first to identify an age-related vulnerability of hippocampal dentate gyrus granule cells to hyperthermia-related modification of their nucleotide gated channels that resulted in activation/ hyperpolarization without associated cell death. In this modified state, spontaneous seizures occurred. This transition in cellular function was associated with the appearance of T2-bright imaging changes imaging changes not only in the hippocampus, but also in non-hippocampal sites relevant to the subsequent development of temporal lobe epilepsy, The novel observation provided a model pertinent not only to the epileptic aspects of temporal lobe sclerosis, but also to possibly associated disturbances of learning, memory, and perhaps other behaviors. Dr. Baram and her colleagues have also devoted considerable attention to advancing understanding of the pathophysiology of infantile spasms. They were the first to identify the involvement of stress-responsive corticotrophin releasing hormone in the development of relevant seizures in rat pups. As an endocrinologist, Dr. Baram directed further highly influential work at two questions: the role that stress might play in epileptogenesis and the efficacy of maternal alleviation of stress in preventing that process.

An astonishing number, range, and depth of valuable observations have been generated in the Baram laboratory. The productivity likely represents another form of “sculpting” – the manner in which Dr. Baram has attracted, influenced, and guided a very large cadre of young investigators to participate in her studies. She is widely known as an extraordinary mentor, possessing skills that she exerts not just locally, in her own laboratory and medical school, but nationally and internationally. Her papers exhibit her capacity for thoughtful construction of hypotheses and designs for related investigation. Twenty-nine major grants attest to the importance granting agencies have attached to her work and have enabled her mentoring of 49 graduate students and 32 medical students and undergraduates. She is Chair of the NIH Study Section on Developmental Brain Disorders and serves as a Trustee of the Lennox-Lombroso Trust that plays a very important role in funding epilepsy research of the highest quality. The impact the Baram laboratory has had is evident in the number of publications and noteworthy scientific presentations it has spawned, including 155 original papers, two-thirds of which are relevant to the themes noted above. The impact of this body of original observations is represented by the fact that the total number of citations to date is 6,763. Forty-three papers have been cited more than 50 times, 17 more than 100 times. Dr. Baram’s impact is further represented by the fact that she has delivered 169 national or international invited lectures and has organized 26 international symposia.

This summary has not touched upon a dozen or more additional important questions to which the beautifully designed and executed research and elegantly written papers completed by Dr. Baram and her colleagues have provided answers and have disclosed novel mechanisms for further research, including some that may advance understanding of the opportunities and restrictions on neural plasticity, or characterization of the function of novel factors such as the role of neuron-restrictive silencing factor in temporal lobe epilepsy. Interest in the role that stress and the alleviation of stress may play in the development of epilepsy and the ensuing function of the individual has placed emphasis on elements that are pertinent to psychology and psychiatry. For more than a century, neurology and psychiatry have not always shared the same scientific basis in their approach to the establishment of pathogenesis. Dr. Baram’s example and achievements suggest that this gulf may be narrowed. There is such a thing as scientific personality. Dr. Baram’s seems to be composed to a considerable extent of the fundamental character of the scientist: an intense motivation meticulously to answer interesting questions and having done so to extend the newly established observation into even more interesting observations that provide a wider context in which successive observations might be placed – such as the effect that maternal care may have in protectively influencing synaptic and neural network responses to perturbation. The personality appears also to be considerably enriched with stamina. She is able to formulate her questions in a manner that is attractive not only to sponsors, but to the large cadre of persons she has attracted to become engaged in research – whether with her or with someone else. She has something of a missionary zeal in terms of converting those who come to her with an interest in being a scientist to persons who actually become scientists. There have been others in our history who have had this a rich mixture of mission, capacity, and vision. Some of their names were Monakow, Sherrington, and Eccles. As can be seen, Dr. Baram is widely engaged. She is also married, to Craig Paul LaFrance. And she has other loves – classical music and medieval French history.