Fen Ze Hu, Ph.D.  Assistant Professor Microbiology and Immunology (pending) Operations Director, Center for Genomic Sciences, ASRI 320 East North Avenue Pittsburgh, PA 15212 Phone: 412-359-8094 Fax: 412-359-6995 Email: fhu@wpahs.org Ph.D., 2004, Drexel University College of Medicine, Philadelphia, Pennsylvania

Keywords:

genomics, bioinformatics bacteria, pathogens, vaccine, antimicrobials

Research Interests:

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 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.

Our work in multiple sclerosis, performed in collaboration with Professor Tom 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:

1. Hu, F.Z., Preston, R.A., Post, J.C., White, J.G., Kikuchi, L., Wang, X., Self, T.W., Allen, G., Stiffler, R.S., McGraw, C., Pulsifer-Anderson, E.A. and G.D. Ehrlich.  Mapping of a gene for pediatric gastroesophageal reflux to chromosome 13q: A collaboration with a family self-help group.  JAMA 284: 325-334, 2000.
2. Hu, F.Z., Post, J.C., Johnson, S., Ehrlich, G.D. and R.A. Preston.  Refined localization of a gene for pediatric gastroesophageal reflux makes HTR2A an unlikely candidate gene.  Hum Genet 107:519-525, 2000.
3. Ehrlich, G.D., Hu, F.Z., Preston, R.A. and J.C. Post.  The spectrum of pediatric gastroesophageal reflux. (letter) JAMA. Dec 27;284(24):3125, 2000.
4. Ehrlich, G.D., Veeh, R., Wang, X., Costerton, J.W., Hayes, J.D., Hu, F.Z., Daigle, B.J., Ehrlich, M.D. and J.C. Post.  Mucosal biofilm formation on middle-ear mucosa in the chinchilla model of otitis media.  JAMA  287:1710-1715,  2002.
5. Hu, F.Z., Donfack, J., Ahmed, A., Dopico, R.J., Johnson, S., Post, J.C., Ehrlich, G.D. and R.A. Preston.  Fine mapping a gene for pediatric gastroesophageal reflux on human chromosome 13q14.  Hum Genet 114;6:562-572, 2004.
6. Shen, K., Antalis, P., Gladitz, J., Sayeed, S., Ahmed, A., Yu, S., Hayes, J., Johnson, S., Dice, B., Dopico, R., Keefe, R., Janto, B., Chong, W., Goodwin, J., Wadowsky, R.M., Erdos, G., Post, J.C., Ehrlich, G.D. and  F.Z. Hu.  Identification, distribution, and expression of novel genes in 10 clinical isolates of nontypeable Haemophilus influenzae. Infect Immun Jun;73(6):3479-3491, 2005.
7. Stoodley, P., Kathju, S., Hu, F.Z., Erdos, G., Levenson, J.E., Mehta, N., Dice, B., Johnson, S., Hall-Stoodley, L., Nistico, L., Sotereanos, N., Sewecke, J., Post, J.C. and G.D. Ehrlich.  Molecular and imaging techniques for bacterial biofilms in joint arthroplasty infections.  Clin Orthop 437:31-40, 2005.
8. Ehrlich G, Hu FZ, Shen K, Stoodley P, Post JC. Bacterial plurality as a general mechanism driving persistence in chronic infections.  Clin Orthop 437:20-24, 2005.
9. Hu, F.Z., Nystrom, A., Ahmed, A., Palmquist, M., Dopico, R., Mossberg, I., Gladitz, J., Rayner, M., Post, J.C., Ehrlich, G.D. and R.A. Preston.  Mapping of an autosomal dominant gene for Dupuytren’s contracture to chromosome 16q in a Swedish family.  Clin Genet 68:424-429, 2005.
10. Braxton, E., Ehrlich, G., Stoodley, P., Hall-Stoodley, L., Veeh, R., Hu, F.Z., Fux, C., Quigley, M. and J.C. Post.  The role of biofilms in neurosurgical device-related infections.  Neurosurg Rev 28;4:249-255.
11. Shen, K., Gladitz, J., Antalis, P., Dice, B., Janto, B., Keefe, R., Hayes, J., Ahmed, A., Dopico, R., Ehrlich, N., Jocz, J., Kropp, L., Yu, S., Nistico, L., Greenberg, D.P., Barbadora, K., Preston, R.A., Post, J.C., Ehrlich, G.D. and F.Z. Hu.  Characterization, distribution and expression of novel genes among eight clinical isolates of Streptococcus pneumoniae.  Infect Immun 74;1:321-330, 2006.
12. Allegrucci, M., Hu, F.Z., Shen, K., Hayes, J., Ehrlich, G.D., Post, J.C. and K. Sauer  Phenotypic characterization of Streptococcus pneumonia biofilm development.  J Bacteriol, 188;7:2325-2335, 2006.
13. Hall-Stoodley L, Hu FZ, Gieseke A, Nistico L, Nguyen D, Hayes J, Forbes M, Greenberg DP, Dice B, Burrows A, Wackym PA, Stoodley P, Post JC, Ehrlich GD, Kerschner JE.  Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media.  JAMA 296;2:202-211, 2006.
14. Shen, K., Sayeed, S., Antalis, P., Gladitz, J., Ahmed, A., Dice, B., Janto, B., Dopico, R., Keefe, R., Hayes, J., Johnson, S., Yu, S., Ehrlich, N., Jocz, J., Kropp, L., Wong, R., Wadowsky, R.M., Slifkin, M., Preston, R.A., Erdos, G., Post, J.C., Ehrlich, G.D. and F.Z. Hu.  Extensive genomic plasticity in Pseudomonas aeruginosa revealed by identification and distribution studies of novel genes among clinical isolates.  Infect Immun  74(9):5272-5283, 2006.
15. Erdos, G., Sayeed, S., Hu, F.Z., Antalis, P.T., Shen, K., Hayes, J.D., Ahmed, A.I., Johnson, S.L., Post, J.C. and G.D. Ehrlich.   Construction and characterization of a highly redundant Pseudomonas aeruginosa genomic library prepared from 12 clinical isolates:  Application to studies of gene distribution among populations.  Int J Pediatr Otorhinolaryngol 70:1891-1900, 2006.