My laboratory is engaged in three areas of research: 1) bacterial pathogenesis and prevention; 2) human gene mapping and cloning; and 3) understanding immune dysregulation in multiple sclerosis. These three disciplines are united by the high throughput technological and bioinformatic approaches that we bring to bear on them.
The goals of my microbial research are to use ultra-high-throughput genomic sequencing approaches and bioinformatics to identify the common genomic elements and characterize the genomic diversity among clinical strains of chronic bacterial pathogens, and to use this knowledge in the development of novel vaccines and antibacterial strategies. We have recently sequenced the genomes of some 40 strains of Haemophilus influenzae, Streptococcus pneumoniae, and Pseudomonas aeruginosa, which has revealed that all of these species have at the population level a supragenome that is much larger than their core genomes. These data make it likely that bacterial horizontal gene transfer mechanisms, combined with natural polyclonal carriage and infection, serve as a counterpoint to the adaptive host defense mechanisms of vertebrates which also rely upon genic rearrangements and clonal selection within the T- and B-lymphocyte populations.
We are currently using our knowledge of the core genomes of pneumococcus and the NTHi to identify surface-exposed proteins that are universally present among all strains of the species. These proteins are then evaluated as targets for the delivery of Specifically Targeted AntiMicrobial Peptides (STAMPS) as part of a collaborative project with Professor Wenyuan Shi at UCLA. STAMP technology provides a rational means for the development of species-specific antibacterial compounds that will not decimate normal flora, nor engender the development of broad host-range resistance. We are also examining the core surface-exposed proteins as candidates for vaccines as part of a collaborative project with Dr. Peter Nara’s laboratory at Biological Mimetics. As part of the vaccine project, we are evaluating all candidates for the presence of decotopes which will be removed by protein engineering to develop vaccine targets that induce a classical naïve immune response.
In the realm of human genetics, we are currently using a sequence capture approach combined with next generation DNA sequencing to completely sequence the 6 megabase GERD1 linkage region on chromosome 13q from patients with severe pediatric gastroesophageal reflux to identify the causative mutation(s) for this debilitating disease. We are also working with Dr. Ake Nystrom at the University of Nebraska to clone the gene for Dupuytren’s contracture, which we recently mapped to chromosome 16q. More recently we have been combining our pathogen and human genomics research programs by working on the development of a combined sequence capture – high throughput sequencing approach to identify, in a massively parallel fashion, viral integration sites within the host genome.
Our work in multiple sclerosis, performed in collaboration with Professor Thomas Scott at Allegheny General Hospital, is designed to identify a diagnostic gene expression signature among CD4+ cells that will be prognostic for resistance to standard interferon-based therapies.
Selected Publications (See all Fen Hu's publications in PubMed.)
"Biofilm formation by ica-positive and ica-negative strains of Staphylococcus epidermidis in vitro"
Dice B, Stoodley P, Buchinsky F, Metha N, Ehrlich GD, and Hu FZ
Biofouling, 25(4):367-375, 2009
"Medical treatment of craniosynostosis: recombinant Noggin inhibits coronal suture closure in the rat craniosynostosis model"
Shen K, Krakora SM, Cunningham M, Singh M, Wang X, Hu FZ, Post JC, and Ehrlich GD
Orthod. Craniofac. Res., 12:254-262, 2009
"Gene expression differences in infected and non-infected middle ear complementary DNA libraries"
Kerschner JE, Horsey E, Ahmed A, Erbe C, Khampang P, Cioffi J, Hu FZ, Post JC, and Ehrlich GD
Archives of Otolaryngology-Head & Neck Surgery, 135(1):33-39, 2009
"Differential expression of chaperonin containing T-complex polypeptide (CCT) subunits during fetal and adult skin wound healing"
Satish L, Abdulally A, Oswald D, Johnson S, Hu FZ, Post JC, Ehrlich GD, and Kathju S
Cell Stress Chaperones, 13:527-533, 2008
"Characterization of biofilm matrix, degradation by DNase treatment and evidence of capsule downregulation in Streptococcus pneumoniae clinical isolates"
Hall-Stoodley L, Nistico L, Sambanthamoorthy K, Dice B, Nguyen D, Mershon WJ, Johnson C, Hu FZ, Stoodley P, Ehrlich GD, and Post JC
BMC Microbiology, 8:173, 2008
"What makes pathogens pathogenic"
Ehrlich GD, Hiller NL, and Hu FZ
Genome Biology, 9;6: 225, 2008
"Age of child, more than HPV type, is associated with clinical course in recurrent respiratory papillomatosis"
Buchinsky FJ, Donfack J, Derkay CS, Choi SS, Conley SF, Myer III CM, McClay JE, Campisi P, Wiatrak BJ, Sobol SE, Schweinfurth JM, Tsuji DH, Hu FZ, Rockette HE, Ehrlich GD, and Post JC
PLoS ONE, 3(5):e2263, 2008
"Identification of differentially expressed genes in fibroblasts derived from patients with Dupuytren's Contracture"
Satish L, LaFramboise WA, O'Gorman DB, Johnson S, Janto B, Gan BS, Baratz ME, Hu FZ, Post JC, Ehrlich GD, and Kathju S
BMC Med Genomics, 1:10, 2008
"Strain-specific virulence phenotypes of Streptococcus pneumoniae assessed using the Chinchilla laniger model of otitis media"
Forbes ML, Horsey E, Hiller NL, Buchinsky FJ, Hayes JD, Compliment JM, Hillman T, Ezzo S, Shen K, Keefe R, Barbadora K, Post JC, Hu FZ, and Ehrlich GD
PLoS ONE, 3(4):e1969, 2008
"Population-level virulence factors amongst pathogenic bacteria: relation to infection outcome"
Hu FZ and Ehrlich GD
Future Microbiology, 3(1):31-42, 2008
"Insights into the genome of large sulfur bacteria revealed by analysis of single filaments"
Mussmann M, Hu FZ, Richter M, de Beer D, Preisler A, Jørgensen BB, Huntemann M, Glöckner FO, Amann R, Koopman WJ, Lasken RS, Janto B, Hogg J, Stoodley P, Boissy R, and Ehrlich GD
PLoS Biology, 5(9):e230, 2007
"Comparative genomic analyses of seventeen Streptococcus pneumoniae strains: insights into the pneumococcal supragenome"
Hiller NL, Janto B, Hogg JS, Boissy R, Yu S, Powell E, Keefe R, Ehrlich NE, Shen K, Hayes J, Barbadora K, Klimke W, Dernovoy D, Tatusova T, Parkhill J, Bentley SD, Post JC, Ehrlich GD, and Hu FZ
Journal of Bacteriology, 189(22):8186-8195, 2007
"Virulence phenotypes of low-passage clinical isolates of nontypeable Haemophilus influenzae assessed using the chinchilla laniger model of otitis media"
Buchinsky FJ, Forbes ML, Hayes JD, Shen K, Ezzo S, Compliment J, Hogg J, Hiller NL, Hu FZ, Post JC, and Ehrlich GD
BMC Microbiology, 7:56, 2007
"Characterization and modeling of the Haemophilus influenzae core and supragenomes based on the complete genomic sequences of Rd and 12 clinical nontypeable strains"
Hogg JS, Hu FZ, Janto B, Boissy R, Hayes J, Keefe R, Post JC, and Ehrlich GD
Genome Biology, 8(6):R103, 2007
"Gene expression changes in peripheral blood mononuclear cells from multiple sclerosis patients undergoing beta-interferon therapy"
Singh MK, Scott TF, LaFramboise WA, Hu FZ, Post JC, and Ehrlich GD
Journal of the Neurological Sciences, 258(1-2): 52-59, 2007