LATS Senior Awards


J. Enrique Silva

Winner 1995


Resumee

Dr. J. Enrique Silva, was born in Santiago, Chile. He studied Medicine at the University of Chile School of Medicine from where he graduated summa cum laude in 1968. He was awarded a Honorary Scholarship to start his training and enter the Academic Career at that University. He chose to start his training in Internal Medicine and Experimental Medicine. During his medical student years he performed several independent research projects on the regulation of TSH secretion. His research for entering the Academic Career was on iodine deficiency. His thesis "Mechanisms of Adaptation to Iodine Deficiency in Man and Rat" was approved with maximal distinction. Several publications in national and US journals resulted from this work. In 1974, Dr. Silva joined Dr. Jack H. Oppenheimer's laboratory at Montefiore Hospital, a teaching Hospital of Albert Einstein College of Medicine where he completed his training in clinical and basic endocrinology. His most important contribution during this period was the finding that T3 induces a conformational change in the receptor as assessed by a change in the global charge opposite to that predicted by the binding of T3. The receptor, partially purified by Dr. Silva shifted its migration in ionic exchange columns, which was later used by others to purify the recombinant receptor to homogeneity. At the end of this period, Dr. Silva joined Dr. Larsen, at Harvard Medical School, in Boston, where they did seminal work on the regulation of TSH secretion by T4 and T3. They demonstrated that a substantial fraction of the T3 bound to the receptor in the anterior pituitary is produced locally from T4, by a 5'deiodinating reaction insensitive to PTU. The enzyme involved in this reaction turned out to be the Type II 5'deiodinase later characterized by this group and recently cloned. The concept of local generation of T3 (from T4), increasing the receptor occupancy above the level predicted by plasma T3 was later demonstrated to occur in the brain and it is now widely accepted. At the end of 1977, Dr. Silva returned to his native Chile with the hopes of setting up a research program in his Alma Mater. During these years his research revolved around the demonstration that the mechanisms described in the rat pituitary operated as well in humans. Indirect evidence that this was the case was obtained from detailed analysis of TSH secretion in iodine deficiency and in a fortuitous case of Tg deficiency with lack of T4 synthesis. In 1980, Dr. Silva decided to return to the USA, where he joined Dr. Larsen as Assistant Professor at Harvard Medical School. During the early 80s were also members of this group Michael Kaplan, Theo Visser (in sabbatical leave) and Jack Leonard. This laboratory demonstrated for the first time that T4 to T3 conversion occurs via two distinct pathways catalyzed respectively by Type I and Type II 5'deiodinases (5'D-I and 5'D-II, respectively). Dr. Silva characterized the generation of T3 in the brain in vivo and how is affected by hypothyroidism. It was demonstrated that not only fractional conversion of T4 to T3 is increased in hypothyroxinemia (due to the increase in 5'D-II), but also that T3 degradation or disposal by the brain is reduced in this condition. In 1983, Dr. Silva was awarded the Van Meter Prize of the American Thyroid Association for his contributions to the understanding of the responses of the body to iodine deficiency. His lecture was entitled "Response to iodine deficiency and hypothyroidism. Can we speak about T3 homeostasis?" . In subsequent years, Dr. Silva focused on the finding that the 5'D-II in BAT was stimulated by cold and noradrenergic mechanisms. In work done with Dr. Antonio Bianco, he demonstrated that the generation of T3 resulting from the adrenergic activation of 5'D-II was essential for the response to cold of rats. Since then, most of the research efforts of his group, first at Brigham and Women's Hospital, then at Beth Israel Hospital and lastly in Montreal, at McGill University (Jewish General Hospital), has been co thyroid hormone stimulates thermogenesis using brown adipose tissue as a model. For all this work, for his fostering of young investigators from latin america and Spain, and his frequent presence at latin american scientific meetings and courses, he received in 1995 the LATS Prize. His talk, delivered at the XI International Thyroid Congress in Toronto, was entitle "Thyroid Hormone-Adrenergic Interactions: A Glimpse Through the Brown Adipose Tissue". In his address, Dr. Silva acknowledged the fortune of having as mentors Jack Oppenheimer and Reed Larsen as well as the chance of working with talented colleagues and fellows, a good number of them from south america. Dr. Silva is Professor of Medicine and Physiology at McGill University and Director of the Division of Endocrinology and Metabolism at the Jewish General Hospital, one of the teaching hospitals of this University. In addition to the above mentioned awards, Dr. Silva's contributions to the scientific community have recognized through numerous invited chapters and review articles, invitations to participate in national and international symposia, by sitting at various US, Canadian and international scientific and review committees and by being in the editorial board of several scientific journals. He has over 110 publications.