Hallett Center for Diabetes and Endocrinology
Eduardo A. Nillni, PhD
Associate
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. More
about Nillni
Representative Publications
- Nillni EA and Sevarino KA. The biology of proTRH-derived peptides.
Endocrine Reviews 1999; 20:599-648.
- Nillni EA. Neuroregulation of proTRH biosynthesis and processing.
Endocrine 1999;10:185-199.
- Nillni EA and Pescovitz OH. Posttranslational processing of
progrowth hoemone releasing hormone. Endocrinology 1999;
140:5817-5827.
- Nillni EA, Aird F, Todd, RB, Seidah NG and Koenig J. PreproTRH178-199
and two novel peptides (pFQ7 and pSE14) derived from its processing,
which are produced in the paraventricular nucleus of the rat hypothalamus,
are regulated during suckling. Endocrinology 2001; 142:896-906.
- Nillni EA, Vaslet C, Harris M, Hollenberg A, Bjorbak C, Flier
JS. Leptin Regulates Prothyrotropin-releasing Hormone Biosynthesis.
Evidence for Direct and Indirect Pathways. J Biol Chem
2000; 275:36124-36133.
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