Research
Interests:
1.
Sexually Transmitted Infection: Chlamydial Cellular and
Molecular Parasitology
Chlamydiae are
Gram-negative eubacteria that replicate strictly inside
eukaryotic cells. Chlamydia trachomatis is the
most prevalent cause of sexually transmitted infection and
preventable blindness. Though C. trachomatis infection
is mostly asymptomatic or manifests only mild urogenital
symptoms, it often results in devastating complications
including infertility, chronic pelvic pain, ectopic pregnancy,
premature birth and arthritis .
C. pneumoniae is a common pathogen in the
respiratory system and is also highly significant contributory
factor of atherosclerosis. We
have identified peptide deformylase as an essential enzyme
for chlamydial growth. We are characterizing this
enzyme and exploring its inhibition for the prevention and
treatment of chlamydial diseases. We are also interested
in identifying novel host factors that support chlamydial
infection.
2.
Mammalian Cell Biology: Signaling Regulation of Protein
Ectodomain Shedding
Numerous
membrane proteins undergo regulated proteolytic cleavage
at the cell surface to release their extracellular domains.
Ectodomain shedding generates soluble growth factors, cytokines,
proteases, receptors and adhesins, and consequently regulates
cell proliferation, differentiation, migration, and apoptosis.
While normal physiological processes including development,
immunity and wound healing requires ectodomain shedding,
its disregulation contributes to the development of cancer,
inflammatory and autoimmune reactions, cardiovascular disease
and neurodegeneration. Aiming at the intervening with the
development of these diseases, we study the signaling mechanisms
that underlie the regulation of ectodomain shedding under
a variety of physiological and pathological conditions.
Selected
Publications:
Li, X., L. Perez,
Z. Pan, H. Fan. 2007. The transmembrane domain of TACE regulates
protein ectodomain shedding. Cell Res. [Epub ahead
of print].
Balakrishnan, A.,
L. Wang, X. Li, P. Ohman-Strickland, P. Malatesta, H. Fan.
2007. Inhibition of chlamydial infection in the genital
tract of female mice by topical application of a peptide
deformylase inhibitor. Microbiol. Res. [Epub ahead
of print].
Perez, L., X. Li,
J. Kerrigan, H. Fan. 2007. Substitution of methionine 435
with leucine, isoleucine, and serine in tumor necrosis factor
alpha converting enzyme inactivates ectodomain shedding
activity. Biochem. Cell Biol. 85:141-149.
http://article.pubs.nrc-cnrc.gc.ca/ppv/RPViewDoc?issn=0829-8211&volume=85&issue=1&startPage=141
Balakrishnan, A.,
B. Patel, S. A. Sieber, D. Chen, N. Pachikara, G. Zhong,
B. F. Cravatt, and H. Fan. 2006. Metalloprotease inhibitors
GM6001 and TAPI-0 inhibit the obligate intracellular human
pathogen Chlamydia trachomatis by targeting peptide deformylase
of the bacterium. J. Biol.
Chem. 281:16691-16699 .
http://www.jbc.org/cgi/reprint/M513648200v1
Li,
X., H. Fan. 2004. Loss of ectodomain shedding due to mutations
in the metalloprotease and cysteine-rich/disintegrin domains
of the tumor necrosis factor-a converting enzyme (TACE).
J. Biol. Chem. 279:27365-75.
http://www.jbc.org/cgi/content/full/279/26/27365
Fan,
H., C.W. Turck, R. Derynck. 2003. Characterization of growth
factor-induced serine phosphorylation of tumor necrosis
factor-a converting enzyme (TACE) and of an alternatively
translated polypeptide. J. Biol. Chem. 278:18017-18027.
http://www.jbc.org/cgi/content/full/278/20/18617
UMDNJ/Rutgers
Molecular BioScience Graduate Program Memberships:
The
Graduate Program in Physiology and Integrative Biology (PIB)
The Graduate Program in Molecular Genetics, Microbiology
and Immunology (MGMI)
Current
Lab Members:
Xiaofeng
Bao, Ph.D., Postdoctoral Fellow
Niseema
Pachikara, B.S., Ph.D. Candidate (UMDNJ-Rutgers Joint Molecular
BioSciences Program)
Liliana
Perez, B.S., Ph.D. Candidate (UMDNJ-Rutgers Joint Molecular
BioSciences Program)
Winnie
Wu, M.D., M.Sc., Ph.D. student (UMDNJ-Rutgers Joint Molecular
BioSciences Program)
Jason
I. Levin, Rutgers Senior
Shaival
Shah, Work/study student
Former
Lab Members:
Xiaojin Li, M.D.,
Ph.D., Postdoctoral Fellow/Research-teaching Specialist
(2002-2007), Current Affiliation: American Red Cross
Junwei Deng, M.D.,
M.Sc., Research-teaching Specialist (2004), Current Affiliation:
Central South University Xiangya Medical School
Amit Balakrishnan
, Ph.D., B.Pharm., Joint Molecular
BioSciences PIB Student (2002-2006), Current Affiliation:
Navy Medical Research Center
Bhairavi Patel, B.S.,
Work/study student (2001-2004), Current Affiliation: Unknown
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