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Michael J. Leibowitz
Professor
UMDNJ-Robert Wood Johnson Medical School
Dept. of Molecular Genetics and Microbiology
675 Hoes Lane. Room 705
Piscataway. NJ 08854
(732) 235-4795
FAX - 5223
leibowit@umdnj.edu |
Interaction of malaria parasites with mammalian host cells
The prion-like [KIL-d] cytoplasmic genetic element of yeast places the
M double-stranded RNA genome segment of killer virus of yeast under epigenetic
regulation in cells carrying [KIL-d] and the virus. The molecular nature
of the [KIL-d] element and the mechanism of epigenetic regulation are
being studied. The prion hypothesis is being tested
by cloning the putative prion-encoding gene.
Group I self-splicing introns are ribozymes whose function is essential to
various microorganisms that harbor these insertions in essential genes. Since
group I introns are not found in humans. inhibitors of group I intron splicing
are potential antimicrobial agents. We have characterized several group I
introns of pathogenic fungi. and have shown that the antifungal drug pentamidine
inhibits group I intron splicing in Candida albicans. In collaboration
with Y. Zhang we are studying the molecular basis of small molecule inhibition
of group I intron ribozyme catalysis.
Novel therapeutic agents and delivery systems are being studied
(collaboration with S. Stein and P.J. Sinko). Multipartite antisense compounds
targeting the 5'-untranslated region of mRNA have been shown capable of
down-regulation of the HER-2/neu oncogene in cell-free expression systems; their
action in cells is now being studied. Novel inhibitors of HIV-1 replication have
been developed including a peptide-derived inhibitor of the viral Tat regulatory
protein and a novel non-nucleoside reverse transcriptase inhibitor. In order to
deliver these therapeutic agents and target them to specific cells and
tissues. a series of novel polymeric drug delivery technologies have been
developed. These include a carrier molecule that can transport and target
therapeutic agents to specific cells. and an injectable hydrogel system for
long-term delivery of drugs. These technologies are being developed for delivery
of small molecule drugs as well as proteins and antisense agents. as well as for
immunotherapy applications.
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