Molecular genetics of pancreatic ductal adenocarcinoma (PDA) and head and neck squamous cell carcinoma (HNSCC), as well as mouse modeling for both cancer types.
PDA and HNSCC and 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. Kras for PDA and Cyclin D1 for HNSCC). 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. Using tissue-specific genetic-engineered techniques (e.g. conditional knock-out) and our knowledge of the genetic profiles of human PDA and HNSCC, we have successfully generated several genetic engineered mouse models (GEMM) that mirror the tumorigenesis of human PDA and HNSCC at both genetic and histologic levels. These GEMM are being interrogated to broaden our understanding of cancer development, progression, and metastasis, as well as in the development of early detection and novel treatment options.
W. Qiu, X. Li, H. Tang, A. S. Huang, A. A. Panteleyev, D. M. Owens, G. H. Su. Conditional activin reporter type IB (Acvr1b) knockout mice revealed hair loss abnormality. Journal of Investigative Dermatology 2011, 131:1067-76 (Epub Dec 2010).
A. C. Birkeland, Y. Larrabee, D. T. Kent, C. Flores, G. H. Su, J. H. Lee, J. Haddad. Novel IRF6 mutations in Honduran Van Der Woude syndrome patients. Mol Med Report 2011, 4(2):237-41 (Epub 2011, Jan 11)
Y. C. Larrabee, A. C. Birkeland, D. T. Kent, C. Flores, G. H. Su, J. H. Lee, J. Haddad. Association of common variants, not rare mutations, in IRF6 with non-syndromic clefts in a Honduran population. Laryngoscope 2011, 121:1756-9
J. DiNorcia, M. K. Lee, D. N. Moroziewicz, M. D. Winner, P. Suman, F. Bao, H. E. Remotti, Y. S. Zou, S. F. Yan, W. Qiu, G. H. Su, A. M. Schmidt, J. D. Allendorf. RAGE gene deletion inhibits the development and progression of ductal neoplasia and prolongs survival in a mouse model of pancreatic cancer. Journal of Gastrointestinal Surgery 2012, 16:104-12 (Epub Nov 4, 2011).
W. Qiu, F. Sahin, C.A. Iacobuzio-Donahue, Dario Garcia-Carracedo, W. M. Wang, Chia-Yu Kuo, Dan E. Arking, A. M. Lowy, R. H. Hruban, H. E. Remotti, G. H. Su. Disruption of p16 and Activation of Kras in Pancreas Increases Ductal Adenocarcinoma Formation and Metastasis in vivo. Oncotarget 2011, 2:862-73 (Epub Nov 23, 2011).
C. J. Lennon, A. C. Birkeland, J. A. Pacheco Nunez, G. H. Su, P. Lanzano, E. Guzman, K. Celis, S. B. Eisig, D. Hoffman, M. T. Guerra Rendon, H. Ostos, W. K. Chung, J. Haddad, Jr. Association of candidate genes with nonsyndromic clefts in Honduran and Colombian populations. Laryngoscope 2012, 122:2082-7 (Epub July 2, 2012).
W. Qiu and G. H. Su. Challenges and advances in mouse modeling for human pancreatic tumorigenesis and metastasis. Cancer and Metastasis Review, 2013 June;32(1-2):83-107 (Epub Nov 1, 2012).
W. Qiu and G. H. Su. Development of orthotopic pancreatic tumor mouse models. Methods Mol Biol. 2013; 980:215-23.
D. Gu, H. Liu, G. H. Su, X. Zhang, H. Chin-Sinex, H. Hanenberg, M. Mendonca, H. E. Shannon, E. G. Chiorean, J. Xie. Combining hedgehog signaling inhibition with focal irradiation on reduction of pancreatic cancer metastasis. Molecular Cancer Therapeutics 2013 June; 12(6):1038-48 (Epub March 6, 2013).
R. D. Dinnen, Y. Mao, W. Qiu, N. Cassai, V. N. Slavkovich, G. Nichols, G. H. Su, P. Brandt-Rauf, R. L. Fine. Redirecting apoptosis to aponecrosis induces selective cytotoxicity to pancreatic cancer cells through increased ROS, decline in ATP levels, and VDAC. Molecular Cancer Therapeutics 2013; 12(12):2792-803.
D. Garcia-Carracedo, A. T. Turk, S. A. Fine, N. Akhavan, B. C. Tweel, R. Parsons, J. A. Chabot, J. D. Allendorf, J. M. Genkinger, H. E. Remotti, G. H. Su. Loss of PTEN expression is associated with poor prognosis in patients with intraductal papillary mucinous neoplasms of the pancreas. Clin Cancer Research 2013 (Epub Nov 12, 2013).
D. Garcia-Carracedo, Z. Chen, W. Qiu, A. S. Huang, S. M. Tang, R. H. Hruban, G. H. Su. PIK3CA mutations in mucinous cystic neoplasms of the pancreas. Pancreas 2013 (accepted).
W. Qiu, G. Tong, A. T. Turk, L. G. Close, S. M. Caruana, G. H. Su. Oncogenic PIK3CA is overexpressed and mutated in salivary duct carcinoma. BioMed Research International 2013 (acceptable upon revision).
Honors and Awards
Permanent member, NIH Peer Review Study Section-TPM
Grant reviewer, AACR-PanCAN.
Editorial Board, Journal of Otolaryngology (OMICS)
Reviewer, Cancer Council NSW Australia.
External Site Visitor, Site visit for the NCI Cancer Biomarkers Research Group-Early Detection Research Network Laboratories.
Ad Hoc Reviewer, NIH Peer Review Study Section-TPM, TMEN, MONC, Omnibus.
Florence Irving Assistant Professor of Otolaryngology, Irving Institute for Clinical and Translational Research, Columbia University.
2007, 2008, 2009, 2010
Reviewer, Peer Review Study Sections, Department of Defense (DOD)-Congressionally Directed Medical Research Programs (CDMRP)
Member, the Executive Board of the Pancreas Center at the Columbia University Medical Center
Faculty Member, the Herbert Irving Cancer Research Center at the Columbia University Medical Center
Member, the Editorial Board of the International Journal of Gastrointestinal Cancer, Humana Press.
Co-chair, NIH GI Joint MMHCC-SPORE Meeting, Washington, D.C.
Member, the Research Advisory Council of the Department of Pathology, The Johns Hopkins University