Research Interest:
1. Understanding the role of the transmembrane domains of fusion
proteins in membrane fusion.
2. Elucidating the functions of sterols in the nematode (worm) Caenorhabditis
elegans.
Description:
Steroid endocrinology: the function of cholesterol in Caenorhabditis
elegans.
The nematode Caenorhabditis elegans is a model organism for studies
of growth and development in multicellular animals. Its genome sequence
has been completed, and the descent of every one of the 959 cells
of the adult have been traced from the unicellular zygote. This
allows developmental events to be studied at a level of molecular
and cellular detail that is not possible in any other organism.
C. elegans requires small amounts of cholesterol in its diet for
normal growth, reproduction and development, but the reason for
this requirement is not known. We postulate that cholesterol is
used by the animal to synthesize essential steroid hormones. We
have found that dietary cholesterol is concentrated within the animal
in five discrete cells, which are candidates for hormone-producing
cells. Further, certain cholesterol metabolites can substitute for
cholesterol in wild-type animals, but not in animals lacking the
gene for one particular sterol-sensing protein. We are using a combination
of microscopic, biochemical and genetic approaches to understand
the metabolic fate of the ingested dietary cholesterol, and the
function of the hormone-like cholesterol metabolites. We expect
these studies to reveal the mechanisms of biosynthesis and action
of a steroid hormone at an unprecedented level of detail, and to
provide new insights into the evolution of steroid hormone actions.
Publications:
Lenard, J. and Wadsworth, W.G. 2000. Toward steroid endocrinology:
Cholesterol accumulation in C. elegans. Abstracts, East Coast Worm
Meeting 2000, Atlanta GA p. 46
Lenard, J. 1999. Host cell protein kinases in nonsegmented negative-strand
virus (mononegavirales) infection. Pharmacology and Therapeutics
83: 39-48.
Lenard, J. 1999. Virus membranes In Encyclopedia of Virology,
2nd Edition. Edited by A. Granoff and R. Webster. Pp 1920-1925.
Academic Press Ltd. London.
Cleverley, D.Z. and Lenard, J. 1998. The transmembrane domain in
viral fusion: Essential role for a conserved glycine residue in
vesicular stomatitis virus G protein. Proceedings of the National
Academy of Sciences, USA 95: 3425-3430.
Cleverley, D.Z., Geller, H.M. and Lenard, J. 1997. Characterization
of cholesterol-free insect cells infectible by baculoviruses: Effects
of cholesterol on VSV fusion and infectivity and on cytotoxicity
induced by influenza M2 protein. Experimental Cell Research 233:
288-296.
Cleverley, D.Z. and Lenard, J. 1998. The transmembrane domain in
viral fusion: Essential role for a conserved glycine residue in
vesicular stomatitis virus G protein. Proc. Natl. Acad. Sci. USA
95, 3425-3430.
Merris, M., Wadsworth, W.G. and Lenard, J. 2001. Sterol function
in C. elegans. Abstracts, Intl. C. Elegans meeting, Los Angeles
CA. June, 2001
Lenard, J. and Greenfield, N.J. 2001. Alternate conformations of
transmembrane domain peptides. Abstracts, Biophysical Society Annual
Meeting, Boston MA. February, 2001.
Staff:
Jessica Kraeft, B.S., Research Teaching Specialist
Mark Merris, M.S., Research Teaching Specialist
Limei Zhuo, M.S., Research Teaching Specialist
Graduate Program Membership:
Biochemistry (joint and UMDNJ)
Microbiology (joint and UMDNJ)
Pharmacology
Physiology
Cell and Developmental Biology
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