Research Interests:

1. Sexually Transmitted Infections

1) 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 are interested in identifying novel host factors that control chlamydial infection.

2) Development of New Prophylaxes and Therapies for Sexually Transmitted Infections

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 and other sexually transmitted infections including gonorrhea. We also attempt to identify novel antimicrobials and investigate the underlying targeting mechanism.

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, aging, 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.

Funding Agencies

1) National Institute of Allergy and Infectious Diseases (Current)

2) National Institute on Aging (Current)

3) American Heart Association (Past)

4) New Jersey Commission on Cancer Research (Past)

5) Foundation of UMDNJ (Past)

Selected Publications:

Pachikara, N., H. Zhang, Z. Pan, S. Jin, H. Fan. 2009. Productive Chlamydia trachomatis lymphogranuloma venereum 434 infection in cells with augmented or inactivated autophagic activities. FEMS Microbiol. Lett. 292:240-249.

http://www3.interscience.wiley.com/cgi-bin/fulltext/121670538/PDFSTART

Balakrishnan, A., L. Wang, X. Li, P. Ohman-Strickland, P. Malatesta, H. Fan. 2009. Inhibition of chlamydial infection in the genital tract of female mice by topical application of a peptide deformylase inhibitor. Microbiol. Res. 164:338-346.

http://www.sciencedirect.com/science/journal/09445013

Li, X., L. Perez, Z. Pan, H. Fan. 2007. The transmembrane domain of TACE regulates protein ectodomain shedding. Cell Res. 17:985-998.

http://www.nature.com/cr/journal/v17/n12/pdf/cr200798a.pdf

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, PhD, Postdoctoral fellow

Christopher B. Oey, BS, MSc candidate

Niseema D. Pachikara, BS, PhD candidate (UMDNJ-Rutgers Joint Molecular BioSciences Program)

Steve Pyo , Work/study student

Former Lab Members: