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, 27 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 platform with a 1million SNP chip.
It is our intention to sequence the genes that appear to be significantly in RRP patients based on the above studies.
Selected Publications (See all Farrel Joel Buchinsky's publications in PubMed.)
"ENT infections and the role of biofilms"
Snyder KN, Compliment JM, Buchinsky FJ, Hall-Stoodley L, Stoodley P, and Post JC
The Nurse Practitioner, 34(9):35-39, 2009
"Biofilm formation by ica-positive and ica-negative strains of Staphylococcus epidermidis in vitro"
Dice B, Stoodley P, Buchinsky FJ, Metha N, Ehrlich GD, and Hu FZ
Biofouling, 25(4):367–375, 2009
"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
"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
"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
"Human susceptibility to viral infection: The search for HIV-protective alleles amongst Africans by means of genome-wide studies"
Donfack J, Buchinsky FJ, Post JC and Ehrlich GD
AIDS Research and Human Retroviruses, 10:925-930, 2006
"Unique challenges of obtaining regulatory approval for a multicenter protocol to study the genetics of RRP and suggested remedies"
Sherwood ML, Buchinsky FJ, Quigley MR, Donfack J, Choi SS, Conley SF, Derkay CS, Myer III CM, Ehrlich GD, and Post JC
Otolaryngology-Head & Neck Surgery, 135:189-196, 2006
"Four mutations in epidermodysplasia verruciformis 1 (EVER1) gene are not contributors to susceptibility in RRP"
Donfack J, Buchinsky FJ, Derkay CS, Steinberg BM, Choi SS, Conley SF, Myer III CM, McClay JE, Campisi P, Hu FZ, Preston RA, Abramson AL, Ehrlich GD and Post JC
International Journal of Pediatric Otorhinolaryngology, 70:1235-1240, 2006
"Comparison of oral fluid and serum ELISAs in the determination of IgG response to natural human papillomavirus infection in university women"
Buchinsky FJ, Carter JJ, Wipf GC, Hughes JP, Koutsky LA, and Galloway DA
Journal of Clinical Virology, 35(4):450-453, 2005
"Multicenter initiative seeking critical genes in respiratory papillomatosis"
Buchinsky FJ, Derkay CS, Leal SM, Donfack J, Ehrlich GD, and Post JC
Laryngoscope, 114(2):349-357, 2004
"Sphenoid sinus mucocele: A rare complication of trans-sphenoidal hypophysectomy"
Buchinsky FJ, Gennarelli TA, Strome SE, Deschler DG, and Hayden RE
Ear, Nose and Throat Journal, 80(12):886-888, 2001
"Predicting outcome in pediatric coin ingestion"
Amin MR, Buchinsky FJ, Gaughan JP, and Szeremeta W
International Journal of Pediatric Otorhinolaryngology, 59(3):201-206, 2001
"Do adenoids regrow after excision?"
Buchinsky FJ, Lowry MA, and Isaacson G
Otolaryngology-Head & Neck Surgery, 123(5):576-581, 2000
"T lymphocytes play a critical role in the development of cyclosporin A-induced osteopenia"
Buchinsky FJ, Ma Y, Mann GN, Rucinski B, Bryer HP, Romero DF, Jee WS, and Epstein S
Endocrinology, 137(6):2278-2285, 1996
"Bone mineral metabolism in T lymphocyte-deficient and -replete strains of rat"
Buchinsky FJ, Ma Y, Mann GN, Rucinski B, Bryer HP, Paynton BV, Jee WS, Hendy GN, and Epstein S
Journal of Bone and Mineral Research, 10(10):1556-1565, 1995
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