Huizhou Fan, M.D., Ph.D.
Chlamydial biology with emphasis on host-microbial interaction. Development of antiinfectives, particularly topical microbicide for sexually transmitted infections.
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 sexually transmitted 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 and asthma. C. pneumoniae might also be a cofactor for Alzheimer disease and other neurodegenerative diseases. We are particularly interested in identifying novel host factors that control chlamydial infection.
Antiinfective Development. 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. In addition, we study the molecular mechanisms underlying the regulation of PDF and other genes. We have also identified novel antimicrobial candidates and are investigating the underlying targeting mechanisms.
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.