The candidate, Dr. Ha, has demonstrated a long standing history of commitment to research and academic otolaryngology. This career development award, under the mentorship of Drs. David Sidransky and Joseph Califano is focused on the basic mechanisms underlying adenoid cystic carcinoma (ACC). ? ? ACC is a salivary gland malignancy characterized by persistent local, regional, and distant recurrence despite complete surgical resection and adjuvant radiotherapy. Attempts at improving loco regional control with chemotherapy have been disappointing, and to date, no systemic agent improves control of regional or distant metastases. Better characterization of the genetic alterations involved in ACC tumorigenesis will give us insight into the selection of effective adjuvant therapies or the development of novel therapy. ? ? Promoter hypermethylation as a means of tumor suppressor gene silencing is a significant factor in solid tumor carcinogenesis. We have preliminary evidence that promoter hypermethylation is an important means of tumor suppressor gene inactivation in ACC. The candidate proposes to evaluate commonly methylated tumor suppressor genes in an expanded cohort of ACC samples as well as perform genome wide screening in ACC cell lines in an effort to identify novel methylated genes. Functional and clinical correlation will then be applied to evaluate the biologic significance and prognostic value of these inactivated genes. ? ? The goal of this work is to comprehensively analyze the role of promoter hypermethylation in ACC. The impact on public health lies in establishing this groundwork that will lead to the identification of important biomarkers of tumor behavior and possible avenues of therapeutic intervention in the treatment of this disease. The process of performing these experiments will provide the candidate with the necessary guidance, coursework, and practical training towards becoming an independent investigator as well as furthering the basic science knowledge of adenoid cystic carcinoma. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DE018463-02
Application #
7450963
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Hardwick, Kevin S
Project Start
2007-07-01
Project End
2012-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
2
Fiscal Year
2008
Total Cost
$134,730
Indirect Cost
Name
Johns Hopkins University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Tan, Marietta; Shao, Chunbo; Bishop, Justin A et al. (2014) Aquaporin-1 promoter hypermethylation is associated with improved prognosis in salivary gland adenoid cystic carcinoma. Otolaryngol Head Neck Surg 150:801-7
Liu, Jia; Shao, Chunbo; Tan, Marietta L et al. (2012) Molecular biology of adenoid cystic carcinoma. Head Neck 34:1665-77
Zaboli, David; Tan, Marietta; Gogineni, Hrishikesh et al. (2012) Hyperfractionated radiotherapy with concurrent cisplatin/5-Fluorouracil for locoregional advanced head and neck cancer: analysis of 105 consecutive patients. Int J Otolaryngol 2012:754191
Shao, Chunbo; Sun, Wenyue; Tan, Marietta et al. (2011) Integrated, genome-wide screening for hypomethylated oncogenes in salivary gland adenoid cystic carcinoma. Clin Cancer Res 17:4320-30
Shao, Chunbo; Bai, Weiliang; Junn, Jacqueline C et al. (2011) Evaluation of MYB promoter methylation in salivary adenoid cystic carcinoma. Oral Oncol 47:251-5
Durr, Megan L; Mydlarz, Wojciech K; Shao, Chunbo et al. (2010) Quantitative methylation profiles for multiple tumor suppressor gene promoters in salivary gland tumors. PLoS One 5:e10828
Mithani, Suhail K; Shao, Chunbo; Tan, Marietta et al. (2009) Mitochondrial mutations in adenoid cystic carcinoma of the salivary glands. PLoS One 4:e8493
Ha, Patrick K; Chang, Steven S; Glazer, Chad A et al. (2009) Molecular techniques and genetic alterations in head and neck cancer. Oral Oncol 45:335-9