Description of Research Expertise:
As a surgeon-scientist, my overall goal is to improve our ability cure the most aggressive head and neck cancers while also abating treatment toxicity for ones readily curable by existing therapies. My lab's work has pursued how multiple discrete subpopulations of malignant cells within these tumors cooperatively resist therapy via both tumor cell autonomous mechanisms and crosstalk with the stromal microenvironment. In the process, we have developed the ability to analyze heterogeneity and phenotypic plasticity within cancer cell lines, patient-derived xenografts, and primary human cancer samples based on molecular and functional criteria. My group seeks precise molecular definition of the epigenetic plasticity that promotes homeostasis of tumor cells that retain malignant potential in the face of standard therapy. Our studies integrate known drug resistance mechanisms into a conceptual framework where oncogenic signal dependence is regulated by flux between distinct cell states. Our work demonstrates that activation of oncogenic signaling pathways is remarkably heterogeneous and plastic within any single tumor. As a result, rapid compensation to targeting these pathways occurs not only at the level of signaling networks in individual cells but also through dynamics among diverse cell states cooperatively sustaining cancer progression. We are presently exploiting such intra-tumor diversity as a basis to improve the marginal efficacy of current targeted agents in head and neck cancer therapy with new drug combinations.
Harmeyer KM, Facompre ND, Herlyn M, Basu D: JARID1 Histone Demethylases: Emerging Targets in Cancer Trends Cancer 3 (10): 713-725,2017.
Facompre ND, Harmeyer KH, Basu D: Regulation of oncogenic PI3-kinase signaling by JARID1B Oncotarget 8 (5): 7218-7219,2017.
Facompre ND, Harmeyer KM, Sole X, Kabraji S, Belden Z, Sahu V, Whelan K, Tanaka K, Weinstein GS, Montone KT, Roesch A, Gimotty PA, Herlyn M, Rustgi AK, Nakagawa H, Ramaswamy S, Basu D: JARID1B Enables Transit between Distinct States of the Stem-like Cell Population in Oral Cancers Cancer Res 76 (18): 5538-49,2016.
Facompre ND, Harmeyer KM, Sahu V, Gimotty PA, Rustgi AK, Nakagawa H, Basu D: Targeting JARID1B's Demethylase Activity Blocks a Subset of Its Functions in Oral Cancer Oncotarget 9 (10): 8985-8998,2017.
Facompre ND, Sahu V, Montone KT, Harmeyer KM, Nakagawa H, Rustgi AD, Weinstein GS, Gimotty PA, Basu D: Barriers to Generating PDX Models of HPV-Related Head and Neck Cancer Laryngoscope 127 (12): 2777-2783,2017.
Natsuizaka M, Whelan K, Kagawa S, Tanaka K, Giroux V, Chandramouleeswaran P, Long A, Sahu V, Darling D, Que J, Yang Y, Katz J, Wileyto E, Basu D, Kita Y, Natsugoe S, Naganuma S, Klein-Szanto A, Diehl JA, Bass A, Wong K, Rustgi A, Nakagawa H: Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma Nature Communications 8 (1): 1758,2017.
Basu D, Bewley AF, Sperry SM, Montone KT, Gimotty PA, Rasanen K, Facompre ND, Weinstein GS, Nakagawa H, Diehl JA, Rustgi AK, Herlyn M: EGFR Inhibition Promotes an Aggressive Invasion Pattern Mediated by Mesenchymal-like Tumor Cells within Squamous Cell Carcinomas Mol Cancer Ther 12 (10): 2176-86,2013.
Facompre N, Nakagawa H, Herlyn M, Basu D: Stem-like cells and therapy resistance in squamous cell carcinomas Adv Pharmacol 65 : 235-65,2012.
Basu D, Montone KT, Wang LP, Gimotty PA, Hammond R, Diehl JA, Rustgi AK, Lee JT, Rasanen K, Weinstein GS, Herlyn M: Detecting and targeting mesenchymal-like subpopulations within squamous cell carcinomas Cell Cycle 10 (12): 2008-16,2011.
Basu D, Ngyen TK, Montone KT, Zhang BS, Wang L, Diehl JA, Rustgi AK, Lee JT, Weinstein GS, Herlyn M: Evidence for mesenchymal-like subpopulations within squamous cell carcinomas possessing chemoresistance and phenotypic plasticity Oncogene 29 (29): 4170-82,2010.