J. Christopher Post, M.D., Ph.D., FACS Professor Otolaryngology & Immunology and Microbiology President & Scientific Director, ASRI Medical Director, Center for Genomic Sciences, ASRI Director, Div. of Pediatric Otolaryngology, Allegheny General Hospital 320 East North Avenue Pittsburgh, PA 15212 Phone: 412-359-8169 Fax: 412-359-6995 Email: cpost@wpahs.org M.D., 1983, University of Florida, Gainesville, Florida Ph.D., 1999, University of Pittsburgh, Pittsburgh, Pennsylvania

Keywords:

Biofilms, otitis media, human genetics, human performance, wound healing, tissue engineering

Research Interests:

Ear infections (otitis media, or OM) is the most common illness for which children visit a physician, receive antibiotic prescriptions, and undergo surgery, with a cost of over 5 billion dollars annually. Most children in the U.S. are treated with antibiotics, accounting for 25% of all such prescriptions nationally, and this widespread antibiotic use has led to the development of antibiotic-resistant bacterial strains. OM results from a interplay of genetic and environmental factors, but is primarily an infectious process, and our contribution has been to show that OM is a biofilm disease.

Biofilms are complex organized communities of attached bacteria embedded in an extracellular matrix that display many of the hallmarks of multicellular organisms including: small molecule intercellular communication systems; specialized phenotypes; and differentiated metabolism. Biofilms can be composed of a single species or of multiple species. Confocal laser scanning microscopy (CLSM) of biofilms has revealed the 3-D structure of biofilms and demonstrated that the bacteria live in matrix-enclosed cellular towers separated by open water channels which act as a primitive circulatory system for the delivery of nutrients and removal of metabolic waste products. The CDC estimates that > 60% of bacterial infections in the U.S. are biofilm-related. 

Our Center for Genomic Sciences has had a long-standing interest in biofilms, and have a series of inter-related RO1’s to study biofilm formation of Streptococcus pneumoniae, Hemophilus influenzae and Pseudomonas aureginosa as they relate to ear infections. (Sp)-associated otitis media with effusion (OME) was a mucosal biofilm disease. While we are studying the basic science aspects of biofilms, to include whole genome sequencing and biofilm structural analysis, one of our main efforts is to identify clinically-useful strategies to disrupt and prevent biofilms in vivo. We are using three novel approaches to treat and prevent chronic ear infections: 1) anti-S. pneumoniae-specific Specifically Targeted Anti-Microbial Peptides (STAMP) technology, which employs a bifunctional synthetic peptide for species-specific recognition and killing, thus providing a ‘magic bullet’ that spares normal microbial flora; 2) development of a novel peptide-based anti- S. pneumoniae vaccine that would protect against all strains of S. pneumoniae and 3) techniques to disrupt the biofilm matrix. To accomplish these goals we have assembled a world-class team of collaborators: Professor Wenyuan Shi at UCLA, who has produced a STAMP against S. mutans and Dr. Peter Nara of Biological Mimetics for the vaccine work. The beauty of these approaches is that they address one of our major public health issues: the development of highly-drug-resistant strains of bacteria from the overuse of antibiotics, particularly in the treatment of ear disease.

Selected Publications:

1. 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. 2006 Nov;70(11):1891-900.
2. Hall-Stoodley, L., Hu, F.Z., Gieseke, A., Nistico, L., Nguyen, D., Hayes, J., Forbes, M.,
   Greenberg, D.P., Dice, B., Burrows, A., Wackym, P.A., Stoodley, P., Post, J.C., Ehrlich, G.D. and J.E. Kerschner.  Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media. JAMA. 2006 Jul 12;296(2):202-11.
3. Kerschner, J.E., Meyer, T.K., Burrows, A., Ehrlich, G. and J.C. Post.  Mucin gene cDNA sequence characterization in chinchilla middle ear epithelium. Int J Pediatr Otorhinolaryngol. 2006 Aug;70(8):1449-56. Epub 2006 May 2.
4. 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. F.Z  Hu.  Identification, distribution, and expression of novel genes in 10 clinical isolates of nontypeable Haemophilus influenzae. Infect Immun. 2005 Jun;73(6):3479-91.
5. Erdos, G., Sayeed, S., Antalis, P., Hu, F.Z., Hayes, J., Goodwin, J., Dopico, R., Post, J.C. and G.D. Ehrlich. Development and characterization of a pooled Haemophilus influenzae genomic library for the evaluation of gene expression changes associated with mucosal biofilm formation in otitis media. Int J Pediatr Otorhinolaryngol. 2003 Jul;67(7):749-55.
6. Ehrlich, G.D., Veeh, R., Wang, X., Costerton, J.W., Hayes, J.D., Hu, F.Z., Daigle, B.J., Ehrlich, G.D. and J.C. Post. Mucosal biofilm formation on middle-ear mucosa in the chinchilla model of otitis media. JAMA. 2002 Apr 3;287(13):1710-5.
7. Post, J.C.  Direct evidence of bacterial biofilms in otitis media. Laryngoscope. 2001 Dec;111(12):2083-94.
8. Dingman, J.R., Rayner, M.G., Mishra, S., Zhang, Y., Ehrlich, M.D., Post, J.C. and G.D. Ehrlich.  Correlation between presence of viable bacteria and presence of endotoxin in middle-ear effusions. J Clin Microbiol. 1998 Nov;36(11):3417-9.
9. Aul, J.J., Anderson, K.W., Wadowsky, R.M., Doyle, W.J., Kingsley, L.A., Post, J.C. and G.D. Ehrlich.  Comparative evaluation of culture and PCR for the detection and determination of persistence of bacterial strains and DNAs in the Chinchilla laniger model of otitis media. Ann Otol Rhinol Laryngol. 1998 Jun;107(6):508-13.
10. Bakaletz, L.O., White, G.J., Post, J.C. and G.D. Ehrlich.  Blinded multiplex PCR analyses of middle ear and nasopharyngeal fluids from chinchilla models of single- and mixed-pathogen-induced otitis media. Clin Diagn Lab Immunol. 1998 Mar;5(2):219-24.
11. Rayner, M.G., Zhang, Y., Gorry, M.C., Chen, Y., Post, J.C. and G.D. Ehrlich.  Evidence of bacterial metabolic activity in culture-negative otitis media with effusion. JAMA. 1998 Jan 28;279(4):296-9.
12. Liederman, E.M., Post, J.C., Aul, J.J., Sirko, D.A., White, G.J., Buchman, C.A. and G.D. Ehrlich.  Analysis of adult otitis media: polymerase chain reaction versus culture for bacteria and viruses. Ann Otol Rhinol Laryngol. 1998 Jan;107(1):10-6.
13. Post, J.C., Aul, J.J., White, G.J., Wadowsky, R.M., Zavoral, T., Tabari, R., Kerber, B., Doyle, W.J. and G.D. Ehrlich.  PCR-based detection of bacterial DNA after antimicrobial treatment is indicative of persistent, viable bacteria in the chinchilla model of otitis media. Am J Otolaryngol. 1996 Mar-Apr;17(2):106-11.
14. Buchman, C.A., Doyle, W.J., Skoner, D.P., Post, J.C., Alper, C.M., Seroky, J.T., Anderson, K., Preston, R.A., Hayden, F.G., Fireman, P. and G.D. Ehrlich. Influenza A virus--induced acute otitis media. J Infect Dis. 1995 Nov;172(5):1348-51.
15. Post, J.C., Preston, R.A., Aul, J.J., Larkins-Pettigrew, M., Rydquist-White, J., Anderson, K.W., Wadowsky, R.M., Reagan, D.R., Walker. E.S., Kingsley, L.A., Magit, A.E. and G.D. Ehrlich.  Molecular analysis of bacterial pathogens in otitis media with effusion. JAMA. 1995 May 24-31;273(20):1598-604.