Molecular genetics of head and neck squamous cell carcinoma (HNSCC) and pancreatic ductal adenocarcinoma, as well as mouse modeling for both cancer types.
HNSCC and pancreatic ductal adenocarcinoma are both results of accumulated genetic alterations. Both cancer types share some common oncogenes and tumor-suppressor genes (e.g. p16 and p53), but each has its unique targeted mutations (e.g. Cyclin D1 for HNSCC and K-ras for pancreatic cancer). We continue to compare and contrast the molecular genetic profiles of these two cancer types using both broad genome-scanning approach and candidate-gene approach. By establishing the cancer genetic profiles, we hope to reveal new prognostic markers, discover tumor marker for early detection analysis, and develop chemopreventive and therapeutic treatments that target tumor-specific pathways.
Creating and analyzing mouse models that mirror human tumorigenesis is another one of the major focuses of my laboratory. Tissue-specific knock-out (conditional knock-out) mice based on the genetic profiles of human ductal pancreatic cancer and HNSCC are currently in progress in my laboratory.
1. G. H. Su
, W. Hilgers, M. C. Sheker, D. J. Tang, C. J. Yeo, R. H. Hruban, S. E. Kern. Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene. Cancer Research 1998; 58:2339-2342
2. G. H. Su
, R. H. Hruban, R. K. Bansal, G. S. Bova, D. J. Tang, M. C. Sheker, A. M. Westerman, M. M. Entius, M. Goggins, C. J. Yeo, S. E. Kern. Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers. American Journal of Pathology 1999; 154:1835-1840
3. G. H. Su
, T. A. Sohn, B. Ryu, S. E. Kern. A novel histone deacetylase inhibitor identified by high-throughput transcriptional screening of a compound library. Cancer Research 2000, 60:3137-42.
4. G. H. Su
, R. Bansal, K. M. Murphy, E. Montgomery, C. J. Yeo, R. H. Hruban, S. E. Kern. ACVR1B (ALK4, activin receptor type 1B) gene mutations in pancreatic carcinoma. Proc. Natl. Acad. Sci. USA 2001, 98: 3254-7.
5. G. H. Su
, J. J. Song, E. A. Repasky, M. Schutte, S. E. Kern. Mutation fate of MAP2K4/MKK4 in breast carcinoma. Human Mutation 2002, 19:81.
6. F. Sahin, A. Maitra, P. Argani, N. Sato, N. Maehara, E. Montgomery, M. Goggins, R. H. Hruban, G. H. Su
. Loss of Stk11/Lkb1 expression in pancreatic and biliary neoplasms. Modern Pathology 2003, 16:686-91
7. F. Sahin, W. Qiu, R. E. Wilentz, C. A. Iacobuzio-Donahue, A. Grosmark, G. H. Su
. RPL38, FOSL1, and UPP1 are predominately expressed in the pancreatic ductal epithelium. Pancreas 2005, 30:158-67.
8. W. Qiu, F. Schonleben, H. M. Thaker, M. Goggins, G. H. Su
. A novel mutation of STK11/LKB1 gene leads to the loss of cell growth inhibition in head and neck squamous cell carcinoma. Oncogene 2006, 25:2937-42.
9. W. Qiu, , X. Li, D. J. Ho, L. G. Close, S. Manolidis, B. P. Bennett, G. H. Su
. PIK3CA mutations in head and neck squamous cell carcinoma. Clinical Cancer Research 2006, 12:1441-6.
10. F. Schonleben, W. Qiu, N. T. Ciau, D. J. Ho, X. Li, J. D. Allendorf, H. E. Remotti, G. H. Su
. PIK3CA mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) of the pancreas. Clinical Cancer Research 2006, 12:3851-5.
11. W. Qiu, F. Schonleben, X. Li, G. H. Su
. Disruption of Transforming Growth Factor β-Smad signaling pathway in head and neck squamous cell carcinoma as evidenced by mutations of SMAD2 and SMAD4. Cancer Letter 2007 Jan 8; 245(1-2):163-70. Epub 2006 Feb 14.
12. F. Schonleben, W. Qiu, K. C. Bruckman, N. T. Ciau, X. Li, M. H. Lauerman, H. Frucht, J. A. Chabot, J. D. Allendorf, H. E. Remotti, G. H. Su
. BRAF and KRAS gene mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) of the pancreas. Cancer Letters 2007 May 8; 249(2):242-8. Epub 2006 Nov 9.
13. W. Qiu, G.-X. Tong, S. Manolidis, L. G. Close, A. M. Assaad, G. H. Su
. Novel mutant-enriched sequencing identified high frequency of PIK3CA mutations in pharyngeal cancer. International Journal of Cancer 2008, 122:1189-94 (Epub 2007 Nov 7).
14. F. Schonleben, J. D. Allendorf, W. Qiu, X. Li, D. J. Ho, N. T. Ciau, R. L. Fine, J. A. Chabot, H. E. Remotti, G. H. Su
. Mutational analyses of multiple oncogenic pathways in intraductal papillary mucinous neoplasms of the pancreas. Pancreas 2008, 36: 168-72.
15. V. Vinarsky, R. L. Fine, A. Assaad, Y. Qian, J. A. Chabot, G. H. Su
, H. Frucht. Head and neck squamous cell carcinoma in FAMMM syndrome. Head and Neck, 2009 Epub ahead of print.
16. F. Schonleben, W. Qiu, J. D. Allendorf, J. A. Chabot, H. E. Remotti, G. H. Su
. Molecular analysis of PIK3CA, BRAF, and RAS- oncogenes in periampullary and ampullary adenomas and carcinomas. Journal of Gastrointestinal Surgery, 2009 Epub ahead of print.
Honors and Awards
Reviewer, Cancer Council NSW Australia.2009
External Site Visitor, Site visit for the NCI Cancer Biomarkers Research Group-Early Detection Research Network Laboratories.2009
Reviewer, NIH-TPM, Peer Review Study Section.2008-2011
Florence Irving Assistant Professor of Otolaryngology, Irving Institute for Clinical and Translational Research, Columbia University.2007, 2008, 2009
Reviewer, Peer Review Study Sections, Department of Defense (DOD)-Congressionally Directed Medical Research Programs (CDMRP)2006-present
Member, the Executive Board of the Pancreas Center at the Columbia University Medical Center2003-present
Faculty Member, the Herbert Irving Cancer Research Center at the Columbia University Medical Center2001-present
Member, the Editorial Board of the International Journal of Gastrointestinal Cancer, Humana Press. 2002
Co-chair, NIH GI Joint MMHCC-SPORE Meeting, Washington, D.C.2001-2003
Member, the Research Advisory Council of the Department of Pathology, The Johns Hopkins University