Wendell Yarbrough, MD, MMHC, FACS

Professor of Surgery (Otolaryngology) and of Pathology; Section Chief, Otolaryngology; Co-Director Molecular Virology Research Program; Director, Head & Neck Cancer Program, Smilow Cancer Hospital

Research Interests

DNA Damage; Head and Neck Neoplasms; Salivary Gland Neoplasms; NF-kappa B; Tumor Suppressor Proteins; Human papillomavirus 16; Human Papillomavirus DNA Tests; Diseases

Research Organizations

Surgery: Otolaryngology Surgery: Head & Neck Cancer Surgery Program

Pathology

Faculty Research

HPV

Virology laboratories

Yale Cancer Center: Virus and Other Infection-associated Cancers

Research Summary

Identification of tumor suppressors in head and neck cancers; Understanding of tumor growth; Association between viruses and the development of cancer, particularly the link between the human papillomavirus and head and neck cancers.

Specialized Terms: Head and neck oncology; Salivary oncology; Mouse modeling of human cancer; Human-in-mouse cancer models; Tumor suppressor activity; Molecular defects in cancer; NF-kappa B; NF-kB; Signaling; DNA damage; Human papilloma virus; HPV

Extensive Research Description

I am a surgeon-scientist active in head & neck cancer research for more than two decades. In 2012, I was appointed Chief of Otolaryngology, Director of the Head & Neck Disease Center and Co-Director of the Molecular Virology Program at Yale. Since my arrival, Dr. Issaeva (Co-PI) and I have worked to established a translational research program at Yale focused on head and neck squamous cell carcinoma (HNSCC) with particular interest in HPV-associated cancers. Priorities have been to better understand defects in HPV-associated HNSCC and to identify molecular characteristics that may be essential for tumor formation or maintenance. While prioritizing projects, we took advantage of hypermethylation of HPV+ cancers to explore demethylating drugs and found that these tumors are very responsive to 5-azacytidine (5-aza). We found that 5-aza decreased expression of HPV genes, restored p53 levels and activity, and caused DNA damage, particularly double strand breaks (DSB). Cytotoxicity of 5-aza toward HPV-positive (HPV+) HNSCC was partially attributable to p53 and partially due to DNA damage. Mechanistic studies found that 5-aza-induced DSB required transcription, replication and APOBEC3B, a cytidine deaminase active in virally infected cells.These studies led to an investigator-initiated window trial at Yale Cancer Center. The desire to translate our discoveries for the benefit of patients drives our research. Although we have only relatively recently focused on HPV(+) HNSCC, our research team has made key discoveries and created the infrastructure that has great potential to advance understanding of mechanisms of tumorigenesis and tumor maintenance in HPV-associated HNSCC.

Selected Publications

  • Characterization of HPV and host genome interactions in primary head and neck cancers.

    Characterization of HPV and host genome interactions in primary head and neck cancers. Parfenov M, Pedamallu CS, Gehlenborg N, Freeman SS, Danilova L, Bristow CA, Lee S, Hadjipanayis AG, Ivanova EV, Wilkerson MD, Protopopov A, Yang L, Seth S, Song X, Tang J, Ren X, Zhang J, Pantazi A, Santoso N, Xu AW, Mahadeshwar H, Wheeler DA, Haddad RI, Jung J, Ojesina AI, Issaeva N, Yarbrough WG, Hayes DN, Grandis JR, El-Naggar AK, Meyerson M, Park PJ, Chin L, Seidman JG, Hammerman PS, Kucherlapati R; the Cancer Genome Atlas Network; the Cancer Genome Atlas Network. Proc Natl Acad Sci U S A. 2014 Oct 13. pii: 201416074. [Epub ahead of print]

  • Conclusions about human papillomavirus-related malignancies.

    Conclusions about human papillomavirus-related malignancies. Yarbrough WG, Rosenthal E. Head Neck. 2014 Jun;36(6):826-7. doi: 10.1002/hed.23378. Epub 2013 Sep 2.

Full List of PubMed Publications

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