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.

Selected Publications

Sannigrahi MK, Raghav L, Rich DJ, Schrank TP, Califano JA, Lukens JN, Sun L, Morgan IM, Cohen RB, Lin A, Liu X, Brown EJ, You J, Mirabello L, Mishra SK, Shimunov D, Brody RM, Pearson AT, Gimotty PA, Diab A, Jalaly JB, Basu D.: Tumor-intrinsic and immune-related features associated with treatment failure in HPV-related oropharyngeal cancer JNCI : 2025.

Sannigrahi MK, Raghav L, Diab A, Basu D.: The imprint of viral oncoproteins on the variable clinical behavior among human papilloma virus-related oropharyngeal squamous cell carcinomas Tumour Virus Res. 18 : 2024.

James CD, Otoa1 RO, Youssef AH, Fontan CT, Sannigrahi MK, Windle B, Basu D, Morgan IM: HPV16 genome structure analysis in oropharyngeal cancer PDXs identifies tumors with integrated and episomal genomes Tumor Virus Res (epub): 2024.

Sannigrahi M, Cao AC, Rajagopalan R, Sun L, Brody RM, Raghav L, Gimotty PA, Basu D: A novel pipeline for prioritizing cancer type-specific therapeutic vulnerabilities using DepMap identifies PAK2 as a target in head and neck squamous cell carcinomas Molecular Oncology 18 (2): 336-339,2024.

Sannigrahi MK, Rajagopalan P, Lai L, Liu X, Sahu V, Nakagawa H, Jalaly JB, Brody RM, Morgan IM, Windle BE, Wang X, Gimotty PA, Kelly DP, White EA, Basu D: HPV E6 regulates therapy responses in oropharyngeal cancer by repressing the PGC-1alpha/ERRalpha axis JCI Insight 7 (18): 2022.

Brody RM, Shimunov D, Cohen RB, Lukens JN, Hartner L, Aggarwal C, Duvvuri U, Montone KT, Jalaly J, LiVolsi VA, Carey RM, Shanti RM, Rajasekaran K, Chalian AA, Rassekh H, Cannady SB, Newman JG, Basu D: A benchmark for oncologic outcomes and model for lethal recurrence risk after transoral robotic resection of HPV-related oropharyngeal cancers Oral Oncology 127 : 2022.

Hatterschide J, Castagnino P, Kim HW, Sperry SM, Montone KT, Basu D, White EA: YAP1 activation by human papillomavirus E7 promotes basal cell identity in squamous epithelia eLife 11 : e75466,2022.

Facompre ND, Rajagopalan P, Sahu V, Pearson AT, Montone KT, James CD, Gleber-Netto FO, Weinstein GS, Jalaly J, Lin A, Rustgi AK, Nakagawa H, Califano JA, Pickering CR, White EA, Windle BE, Morgan IM, Cohen RB, Gimotty PA, Basu D.: Identifying predictors of HPV-related head and neck squamous cell carcinoma progression and survival through patient-derived models. Int J Cancer 147 (11): 2020.

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 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.

Academic Contact Information

RESEARCH LAB WEBSITE: http://www.med.upenn.edu/basulab

Perelman Center for Advanced Medicine
South Pavilion, 3rd Floor
3400 Civic Center Blvd.
Philadelphia, PA 19104
Phone: 215-615-3534
Patient appointments: 800-789-7366