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Tumor Biology Section
Carter Van Waes, M.D., Ph.D., Chief
The Head and Neck Surgery Branch (HNSB) includes the Tumor Biology Section and Clinical Genomics, which conduct laboratory clinical studies and trials concerning the pathogenesis, prevention, diagnosis, and treatment of head and neck neoplasms that affect human communication. Head and neck squamous cell carcinoma (HNSCC) is the most prevalent malignancy involving the upper aerodigestive tract which affects voice, speech, taste, smell, hearing, and balance as well as survival. About 52,000 Americans develop neoplasms of the upper aerodigestive tract each year, and approximately 320,000 Americans currently suffer significant impairment of communication and other disability as a result of tumor destruction or ablative surgical and radiation therapy. Despite therapy, more than 8,000 of these patients die annually in the U.S. New modalities for prevention and therapy are needed in order to improve survival and preservation of function.
Current Areas of Interest
Dr. Van Waes with Medical Research Scholars
Program students Danielle Eytan and Suresh
Mohan in the Clinical Genomics Unit.
Anthony Saleh, research fellow, presenting his
work on microRNAs in head and neck cancer
at a conference.
Howard Hughes Scholar Carol Yan presents her
poster on kinase CK2 and transcription factor
p73 in cancer stem cells at a conference.
Genomics and molecular targeted therapeutics for head and neck cancer
A major current focus of the HNSB is to identify and determine the function of genomic alterations that cause head and neck cancers. We have collaborated with the Cancer Genome Atlas Network to complete a comprehensive genomic analysis of HNSCC and multi-platform analysis across 12 cancer types. Additionally, we are completing structural and functional genomic studies of HNSCC lines using genome wide exome, RNA, and RNAi screening, and using genetically engineered mouse models of HNSCC to establish the function of genomic and molecular alterations. These studies have identified key genomic drivers of signal pathway and transcription factor networks previously discovered by our and other laboratories, which will enable investigation of new molecularly targeted agents for therapy and prevention.
Among these, amplifications, deletions, or mutations of receptors and kinases regulating the PI3K, NF-kappaB and MAPK pathways support earlier findings linking co-activation of these pathways and the malignant phenotype. A major subset lacking these alterations have amplifications of Cyclin D1 (CCND1) with Fas Associated Death Domain (FADD) and Inhibitor of Apoptosis gene BIRC2, that regulate proliferation and cell survival or death. Agents targeting PI3K, MAPK and IAPs demonstrate activity and therapeutic promise in preclinical laboratory studies.
For information about employment opportunities, contact:
Carter Van Waes
Chief, Head and Neck Surgery Branch
Clinical Director, NIDCD
Building 10, CRC Room 4-2732
10 Center Drive
Bethesda, MD 20892
Phone: (301) 402-4216
Fax: (301) 402-1140
Clinical and Office Personnel
Office of the Clinical Director
- Clint Allen, collaborator (clinical) (Send email)
- Nicole Schmitt, collaborator (clinical) (Send email)
- David Bianchi, staff clinician (Send email)
- Brian Driscoll, staff clinician (Send email)
- Kenneth Hauck, staff clinician (Send email)
- Hung Kim, staff clinician (Send email)
- Wojchiech Mydlarz, staff clinician (Send email)
- Susannah Wargo, research nurse practitioner (Send email)
- Regal Cameron, intramural office manager (Send email)
- Carter Van Waes, M.D., Ph.D. Clinical Director +1 301 402 4216 (Send e-mail (link sends e-mail))
- Zhong Chen, M.D., Ph.D. Staff Scientist +1 301 435 2073 (Send e-mail (link sends e-mail))
- Hui Cheng Post-Doctoral Visiting Fellow +1 301 451 9171 (Send e-mail (link sends e-mail))
- Paul Clavijo Postdoc Fellow (IRTA) +1 301 594 6091 (Send e-mail (link sends e-mail))
- Adeeb Derakhshan NIH Medical Research Scholar 304-881-3170 (Send e-mail (link sends e-mail))
- Anthony Saleh Research Fellow +1 301 451 9810 (Send e-mail (link sends e-mail))
- Xinping Yang Biologist +1 301 435 2075 (Send e-mail (link sends e-mail))
- Sun L, Clavijo PE, Robbins Y, Patel P, Friedman J, Greene S, Das R, Silvin C, Van Waes C, Horn LA, Schlom J, Palena C, Maeda D, Zebala J, Allen CT. Inhibiting myeloid-derived suppressor cell trafficking enhances T cell immunotherapy. JCI Insight. 2019 Apr 4;4(7). pii: 126853. doi: 10.1172/jci.insight.126853. eCollection 2019 Apr 4.
- Saleh AD, Cheng H, Martin SE, Si H, Ormanoglu P, Carlson S, Clavijo PE, Yang X, Das R, Cornelius S, Couper J, Chepeha D, Danilova L, Harris TM, Prystowsky MB, Childs GJ, Smith RV, Robertson AG, Jones SJM, Cherniack AD, Kim SS, Rait A, Pirollo KF, Chang EH, Chen Z, Van Waes C. Integrated genomic and functional microRNA analysis identifies miR-30-5p as a tumor tuppressor and potential therapeutic nanomedicine in head and neck cancer. Clin Cancer Res. 2019 Feb 5. doi: 10.1158/1078-0432.CCR-18-0716. [Epub ahead of print]
- Day TA, Shirai K, O'Brien PE, Matheus MG, Godwin K, Sood AJ, Kompelli A, Vick JA, Martin D, Vitale-Cross L, Callejas-Varela JL, Wang Z, Wu X, Harismendy O, Molinolo AA, Lippman SM, Van Waes C, Szabo E, Gutkind JS. Inhibition of mTOR signaling and clinical activity of rapamycin in head and neck cancer in a window of opportunity trial. Clin Cancer Res. 2019 Feb 15;25(4):1156-1164. doi: 10.1158/1078-0432.CCR-18-2024. Epub 2018 Nov 12.
- Xiao R, Allen CT, Tran L, Patel P, Park SJ, Chen Z, Van Waes C, Schmitt NC. Antagonist of cIAP1/2 and XIAP enhances anti-tumor immunity when combined with radiation and PD-1 blockade in a syngeneic model of head and neck cancer. Oncoimmunology. 2018 Aug 1;7(9):e1471440. doi: 10.1080/2162402X.2018.1471440. eCollection 2018.
- Cheng H, Yang X, Si H, Saleh AD, Xiao W, Coupar J, Gollin SM, Ferris RL, Issaeva N, Yarbrough WG, Prince ME, Carey TE, Van Waes C, Chen Z. Genomic and transcriptomic characterization links cell lines with aggressive head and neck cancers. Cell Rep. 2018 Oct 30;25(5):1332-1345.e5. doi: 10.1016/j.celrep.2018.10.007
- Sun L, Moore E, Berman R, Clavijo PE, Saleh A, Chen Z, Van Waes C, Davies J, Friedman J, Allen CT. WEE1 kinase inhibition reverses G2/M cell cycle checkpoint activation to sensitize cancer cells to immunotherapy. Oncoimmunology. 2018 Jul 23;7(10):e1488359. doi: 10.1080/2162402X.2018.1488359. eCollection 2018.
- Campbell JD, Yau C, Bowlby R, Liu Y, Brennan K, Fan H, Taylor AM, Wang C, Walter V, Akbani R, Byers LA, Creighton CJ, Coarfa C, Shih J, Cherniack AD, Gevaert O, Prunello M, Shen H, Anur P, Chen J, Cheng H, Hayes DN, Bullman S, Pedamallu CS, Ojesina AI, Sadeghi S, Mungall KL, Robertson AG, Benz C, Schultz A, Kanchi RS, Gay CM, Hegde A, Diao L, Wang J, Ma W, Sumazin P, Chiu HS, Chen TW, Gunaratne P, Donehower L, Rader JS, Zuna R, Al-Ahmadie H, Lazar AJ, Flores ER, Tsai KY, Zhou JH, Rustgi AK, Drill E, Shen R, Wong CK; Cancer Genome Atlas Research Network, Stuart JM, Laird PW, Hoadley KA, Weinstein JN, Peto M, Pickering CR, Chen Z, Van Waes C. Genomic, pathway network, and immunologic features distinguishing squamous carcinomas. Cell Rep. 2018 Apr 3;23(1):194-212.e6. doi: 10.1016/j.celrep.2018.03.063.
- Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015 Jan 29;517(7536):576-82. doi: 10.1038/nature14129.
- Hoadley KA, Yau C, Wolf DM, Cherniack AD, Tamborero D, Ng S, Leiserson MD, Niu B, McLellan MD, Uzunangelov V, Zhang J, Kandoth C, Akbani R, Shen H, Omberg L, Chu A, Margolin AA, Van't Veer LJ, Lopez-Bigas N, Laird PW, Raphael BJ, Ding L, Robertson AG, Byers LA, Mills GB, Weinstein JN, Van Waes C, Chen Z, Collisson EA; Cancer Genome Atlas Research Network, Benz CC, Perou CM, Stuart JM. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. Cell. 2014 Aug 14;158(4):929-44. doi: 10.1016/j.cell.2014.06.049.
- 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; Cancer Genome Atlas Network. Characterization of HPV and host genome interactions in primary head and neck cancers. Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15544-9. doi: 10.1073/pnas.1416074111. Epub 2014 Oct 13.
- Hayes DN, Van Waes C, Seiwert TY. Genetic landscape of human papillomavirus-associated head and neck cancer and comparison to tobacco-related tumors. J Clin Oncol. 2015 Oct 10;33(29):3227-34. doi: 10.1200/JCO.2015.62.1086. Epub 2015 Sep 8.
- Conti MA, Saleh AD, Brinster LR, Cheng H, Chen Z, Cornelius S, Liu C, Ma X, Van Waes C, Adelstein RS. Conditional deletion of nonmuscle myosin II-A in mouse tongue epithelium results in squamous cell carcinoma. Sci Rep. 2015 Sep 15;5:14068. doi: 10.1038/srep14068.
- Mohan S, Vander Broek R, Shah S, Eytan DF, Pierce ML, Carlson SG, Coupar JF, Zhang J, Cheng H, Chen Z, Van Waes C. MEK inhibitor PD-0325901 overcomes resistance to PI3K/mTOR inhibitor PF-5212384 and potentiates antitumor effects in human head and neck squamous cell carcinoma. Clin Cancer Res. 2015 Sep 1;21(17):3946-56. doi: 10.1158/1078-0432.CCR-14-3377. Epub 2015 May 14.
- Leiker AJ, DeGraff W, Choudhuri R, Sowers AL, Thetford A, Cook JA, Van Waes C, Mitchell JB. Radiation enhancement of head and neck squamous cell carcinoma by the dual PI3K/mTOR inhibitor PF-05212384. Clin Cancer Res. 2015 Jun 15;21(12):2792-801. doi: 10.1158/1078-0432.CCR-14-3279. Epub 2015 Feb 27.
- Cash H, Shah S, Moore E, Caruso A, Uppaluri R, Van Waes C, Allen C. mTOR and MEK1/2 inhibition differentially modulate tumor growth and the immune microenvironment in syngeneic models of oral cavity cancer. Oncotarget. 2015 Nov 3;6(34):36400-17. doi: 10.18632/oncotarget.5063.
- Eytan DF, Snow GE, Carlson SG, Schiltz S, Chen Z, Van Waes C. Combination effects of SMAC mimetic birinapant with TNFα, TRAIL, and docetaxel in preclinical models of HNSCC. Laryngoscope. 2015 Mar;125(3):E118-24. doi: 10.1002/lary.25056. Epub 2014 Nov 28.