Eduardo A. Nillni, PhD
- Professor of medicine and molecular and cell biology, Warren Alpert Medical School of Brown University
- National Institutes of Health trainer in molecular biology, cellular biology and biochemistry graduate program, Brown University and Rhode Island Hospital
PhD, The Hebrew University of Jerusalem, Israel, 1982
Eduardo Nillni, PhD, joined the division of endocrinology as a member of the research faculty in 1989. His education included a master's degree in biological sciences from the University of Buenos Aires, Argentina and a PhD from the Hadassah Medical School, Hebrew University of Jerusalem, Israel, where he studied the biochemistry of parasitic protozoa. He did post-doctoral fellowship research on the membrane biology of parasitic protozoa at Tufts-New England Medical Center in Boston, where he then became a member of the faculty. He subsequently shifted his research to the field of endocrinology and has established a highly productive program investigating neuropeptide biosynthesis, regulation and function, and their relationship to energy balance.
Nillni currently is an executive member of the graduate programs admissions committee of the molecular biology, cell biology and biochemistry (MCB) and the MD-PhD program at Brown University, and he also directs one of the graduate courses in the MCB program. He is a reviewer for several journals, including Endocrinology, and an ad hoc reviewer for the Journal of Biological Chemistry and the Journal of Neurochemistry. Nillni is a member of National Institutes of Health metabolism study section FO6, a reviewer for the Canada Institute of Health, and a member of the Canada Research Chairs Program College of Reviewers.
Among his honors, he was the recipient of the 2001 Bruce Selya Award for Research Excellence at Lifespan, and his work recently was featured in a National Science Foundation progress report to the U.S. Congress.
Nillni's laboratory has made substantial contributions to knowledge of the neurobiology of proThyrotropin Releasing Hormone (proTRH), a precursor protein to TRH (pyroGlu-His-ProNH2). The biosynthesis of TRH and other proTRH-derived peptides follows processing mechanisms similar to those described for other secretory peptides, beginning with mRNA-directed ribosomal translation and, followed by post-translational limited proteolysis of the larger precursor, proTRH. This process occurs while proTRH is being transported from the transGolgi network to newly formed immature secretory granules. These granules then mature and are targeted to sites of secretion at the plasma membrane of the cell.
His laboratory demonstrated that cleavage of the TRH precursor to generate biologically active TRH occurs at paired basic residues by the action of two members of the recently discovered family of prohormone convertases 1 and 2 (PC1 and PC2), followed by the action of carboxypeptidase E and D.
In studies on the neuroendocrinology of obesity and energy homeostasis, Nillni directs an extensive research program on the effects of leptin, other neuropeptides and catecholamines in the regulation of Prothyrotropin Releasing Hormone (ProTRH) and proopiomelanocortin (POMC) biosynthesis, processing and secretion. His work in this area provided the first direct evidence for leptin-mediated regulation of preproTRH mRNA expression or TRH prohormone processing. His laboratory also has defined novel proTRH-derived peptides with potential biologic function(s). His current research projects are funded by the National Institutes of Health.
- De Jonghe BC, Hayes MR, Banno R, Skibicka KP, Zimmer DJ, Bowen KA, Leichner TM, Alhadeff AL, Kanoski SE, Cyr NE, Nillni EA, Grill HJ, Bence KK. Deficiency of PTP1B in POMC neurons leads to alterations in energy balance and homeostatic response to cold exposure. Am J Physiol Endocrinol Metab. 2011 Jun;300(6):E1002-11. Epub 2011 Mar 15.
- Perello M, Cakir I, Cyr NE, Romero A, Stuart RC, Chiappini F, Hollenberg AN, Nillni EA. Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level. Am J Physiol Endocrinol Metab. 2010 Dec;299(6):E976-89. Epub 2010 Sep 21. Erratum in: Am J Physiol Endocrinol Metab. 2011 Feb;300(2):E422.
- Ramadori G, Fujikawa T, Fukuda M, Anderson J, Morgan DA, Mostoslavsky R, Stuart RC, Perello M, Vianna CR, Nillni EA, Rahmouni K, Coppari R. SIRT1 deacetylase in POMC neurons is required for homeostatic defenses against diet-induced obesity. Cell Metab. 2010 Jul 4;12(1):78-87.
- Nillni EA. Regulation of the hypothalamic thyrotropin releasing hormone (TRH) neuron by neuronal and peripheral inputs. Front Neuroendocrinol. 2010 Apr;31(2):134-56. Epub 2010 Jan 13. Review.
- Cakir I, Perello M, Lansari O, Messier NJ, Vaslet CA, Nillni EA. Hypothalamic Sirt1 regulates food intake in a rodent model system. PLoS One. 2009 Dec 15;4(12):e8322.