Farrel Joel Buchinsky

Farrel J. Buchinsky, M.D., FACS
Assistant Professor
Microbiology and Immunology & Surgery
Director, Respiratory Papillomatosis Program, Center for Genomic Sciences, ASRI

320 E. North Avenue
Pittsburgh, PA 15212
Phone: 412-359-6725
Fax: 412-359-6995
Email: fbuchins@wpahs.org

MBChB, 1988, University of Cape Town, South Africa

Keywords:

HPV, RRP, papilloma, susceptibility, genes

Research Interests:

Millions of people are infected with one or more types of human papillomavirus (HPV). Many of the more than 100 HPV types are tropic for the genital organs and fall into two general classes: those causing cervical neoplasia; and those causing condylomata (genital warts). In children, unfortunate enough to acquire the condylomatous viral types from their mothers, the infection produces the commonest benign neoplasm of the larynx, recurrent respiratory papillomatosis (RRP). RRP causes voice disturbance which is associated with very significant morbidity and degrades quality of life. Human voice is one of the most defining aspects of our species as it leads directly to our ability to engage in complex communications. Chronic voice disturbance prompts evaluation by an otolaryngologist, and uncontrolled disease may lead to death through airway occlusion. Despite the surgeon being able to diagnose and manage the papillomas, the lesions recur repeatedly since there is no known cure. Most patients must endure multiple surgeries. The disease may go into remission in some but hoarseness often persists for life. We maintain that there is a genetic susceptibility to RRP, and are seeking which genes are involved. Ultimately, we expect that such understanding will enable rational therapy development.

Ongoing collaborations between the RRP Task Force, 19 medical institutions, the Center for Genomic Sciences in Pittsburgh and two patient-support groups has yielded the broadest-based RRP DNA repository ever assembled. The repository is being grown to the size needed for the performance of genome-wide genetic association studies that are sufficiently powered to identify susceptibility genes.

Susceptibility loci will be identified by comparing the patients to their parents as well as to controls and then performing Transmission Disequillibrium Testing and case-control genetic association analyses. Also a quantitative trait locus analysis will be performed in which genotype will be compared to the disease aggressiveness.

Initially, several candidate genes are being explored by genotyping scores of SNPs in each with the Sequenom MASSArray iPLEX. The next step is to conduct genome-wide typing at sufficiently high resolution to detect association by the transmission disequilibrium test; we shall use the Illumina BeadStation with a 300K chip.

It is our intention to sequence the genes that appear to be significantly in RRP patients based on the above studies.

Selected Publications:

Buchinsky, F.J., Romero, D.F., Rucinski, B., Cvetkovic, M., Bryer, H.P., Liang, X.G., Ma, Y.F., Jee, W.S. and S. Epstein. Rapamycin: A bone sparing immunosuppressant? J Bone Miner Res. 1995;10(5):760-768.
Buchinsky, F.J., Ma, Y., Mann, G.N., Rucinski, B., Bryer, H.P., Paynton, B.V., Jee, W.S., Hendy, G.N. and S. Epstein. Bone mineral metabolism in T lymphocyte-deficient and -replete strains of rat. J Bone Miner Res. 1995;10(10):1556-1565.
Romero, D.F., Bryer, H.P., Rucinski, B., Isserow, J.A., Buchinsky, F.J., Cvetkovic, M., Liu, C.C. and S. Epstein. Amylin increases bone volume but cannot ameliorate diabetic osteopenia. Calcif Tissue Int. 1995;56(1):54-61.
Buchinsky FJ, Ma Y, Mann GN, Rucinski B, Bryer HP, Romero DF, Jee WS, Epstein S. T lymphocytes play a critical role in the development of cyclosporin A-induced osteopenia. Endocrinology. 1996;137(6):2278-85.
Mann GN, Sass DA, Chen HK, Buchinsky FJ, Bryer HP, Ma YF, Jee WS, Rucinski B, Epstein S. Short-term systemic insulin-like growth factor-1 is unable to prevent cyclosporin A-induced osteopenia in the rat. Calcified Tissue International. 1996;59(1):38-44.
Buchinsky FJ, Lowry MA, Isaacson G. Do adenoids regrow after excision? Otolaryngology - Head and Neck Surgery. 2000;123(5):576-81.
Amin MR, Buchinsky FJ, Gaughan JP, Szeremeta W. Predicting outcome in pediatric coin ingestion. Int J Pediatr Otorhinolaryngol. 2001;59(3):201-6.
Buchinsky FJ, Gennarelli TA, Strome SE, Deschler DG, Hayden RE. Sphenoid sinus mucocele: A rare complication of transsphenoidal hypophysectomy. Ear Nose Throat J. 2001;80:886-8.
Buchinsky FJ, Derkay CS, Leal SM, Donfack J, Ehrlich GD, Post JC. Multicenter initiative seeking critical genes in respiratory papillomatosis. Laryngoscope 2004;114:349-57.
Hovey AL, Compliment JM, Post JC, Buchinsky FJ. A case of button battery insertion. Advance for Physician Assistants 2005;13;5:28-30.
Compliment JM, Bosworth AD, Post JC, Buchinsky FJ. Rhinolith: An incidental finding in a case of snoring. Advance for Nurse Practitioner 2006;16-17.
Buchinsky FJ, Carter JJ, Wipf GC, Hughes JP, Koutsky LA, Galloway DA. Comparison of oral fluid and serum ELISAs in the determination of IgG response to natural human papillomavirus infection in university women. J Clin Virology 2006;35:450-453.
Donfack J, Buchinsky FJ, Derkay CS, Steinberg BM, Choi SS, Conley SF, Meyer CM, 3rd, McClay JE, Campisi P, Hu FZ, Preston RA, Abramson AL, Ehrlich GD, Post JC. Four mutations in epidermodysplasia verruciformis 1 (ever1) gene are not contributors to susceptibility in RRP. Int J Pediatr Otorhinolaryngol 2006;70:1235-1240.
Sherwood ML, Buchinsky FJ, Quigley MR, Donfack J, Choi SS, Conley SF, Derkay CS, Myer CM, Ehrlich GD, Post JC. Unique challenges of obtaining regulatory approval for a multicenter protocol to study the genetics of RRP and suggested remedies. Otolaryngol Head Neck Surg 2006;135:189-196.
Donfack J, Buchinsky FJ, Post JC, Ehrlich GD. Human susceptibility to viral infection: The search for HIV-protective alleles amongst Africans by means of genome-wide studies. AIDS Res Hum Retroviruses 2006;22(10):925-930.