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Integrative Therapeutics Program
Nicole C. Schmitt, M.D., Otolaryngology Surgeon-Scientist
Research Statement
Our laboratory, which is part of the NIDCD Otolaryngology Surgeon-Scientist Program (OSSP), focuses on researching novel combinations for treatment of head and neck squamous cell carcinoma (HNSCC). Cisplatin chemotherapy is the most commonly used and effective systemic drug for HNSCC, but it has significant adverse effects. Potential strategies to limit the toxicity of cisplatin without affecting anti-tumor efficacy include using alternative agents, combining lower-dose cisplatin with other agents, and using cisplatin in combination with agents that protect normal cells of the inner ear and kidney without altering anti-tumor efficacy. Cell lines and a syngeneic mouse model are used to investigate the efficacy of cisplatin in combination with targeted biologic agents and putative protective agents.
Data from our lab suggest that cisplatin may have immune-modulating effects in the tumor microenvironment, and our preclinical mouse studies show that cisplatin enhances the efficacy of anti-PD-1 immunotherapy. We are also investigating drugs that block inhibitor of apoptosis proteins (IAPs). Our preclinical data suggest that IAP inhibitors also induce an anti-tumor immune response, and these drugs may be a less toxic replacement for platinum chemotherapy.
Another interest of the lab is to characterize and prevent cisplatin-induced hearing loss in head and neck cancer patients. A clinical study is currently underway to determine whether HNSCC patients who are taking statin drugs for high cholesterol may have a lower risk of developing hearing loss from cisplatin chemoradiation.
Collaborators
Lab Personnel
- Nicole C. Schmitt, M.D. Otolaryngology Surgeon-Scientist +1 301 827 5619 (Send e-mail)
- Zhouhong (Amy) Cao, M.D. Biologist, Lab Manager (contractor) +1 301 827 5619 (Send e-mail)
- Sreenivasulu Gunti Scientist (contractor) +1 301 827 5619 (Send e-mail)
- Wen Da Ye Medical Student MSRP Program +1 301 827 5619 (Send e-mail)
- Youji Hong Post Baccalaureate IRTA +1 301 827 5619 (Send e-mail)
Left to right: Nicole C. Schmitt, M.D.; Zhouhong (Amy) Cao, M.D.; Sreeni Gunti, Ph.D.; Wen Da Ye, BS; Youji Hong, BS.
Selected Publications
- 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; doi: 10.1080/2162402X.2018.1471440.
- Spielbauer K, Cunningham L, Schmitt N. PD-1 inhibition minimally impacts cisplatin-induced toxicities in a murine model. Otolaryngol – Head and Neck Surg 2018 Aug;159(2):343-346. doi: 10.1177/0194599818767621. Epub 2018 Apr 3.
- Tran L, Allen CT, Xiao R, Moore E, Davis R, Park SJ, Spielbauer K, Van Waes C, Schmitt NC. Cisplatin alters anti-tumor immunity and synergizes with PD-1/PD-L1 inhibition in head and neck squamous cell carcinoma. Cancer Immunol Res 2017;5:1141-1151.
- Gilbert MR, Sharma A, Schmitt NC, Johnson JT, Ferris RL, Duvvuri U, Kim S. A 20-year review of 75 cases of salivary duct carcinoma. JAMA Otolaryngol Head Neck Surg. 2016 May 1;142(5):489-95. doi: 10.1001/jamaoto.2015.3930.
- Schmitt NC, Sharma A, Gilbert MR, Kim S. Early T stage salivary duct carcinoma: Outcomes and implications for patient counseling. Otolaryngol Head Neck Surg 2015; pii: 0194599815601659.
- Schmitt NC, Ferris RL. STAT1 activation is enhanced by cisplatin and variably affected by EGFR inhibition in HNSCC cells. Mol Cancer Ther 2015; pii: molcanther.0305.2015.
- Schmitt NC, Rubel EW, Nathanson NM. Cisplatin-induced hair cell death requires STAT1 and is attenuated by epigallocatechin gallate. J Neurosci 2009; 29:3843–3851.