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The Atul Bedi Lab in the Head and Neck cancer research program provides fundamental insights into the molecular determinants and mechanisms by which tumor cells evade death signals entrained by the immune system and anticancer agents. Their recent studies show that tumor-induced immune tolerance limits the in vivo anti-tumor efficacy of tumor-targeted antibodies and that the tumor cell-autonomous expression of transforming growth factor-b (TGF-b) is a key molecular determinant of the de novo or acquired resistance of cancers to EGFR-targeted antibody. Their laboratory has developed novel bi-functional antibody-based strategies to simultaneously counteract immune tolerance in the tumor microenvironment and to enhance the anti-tumor efficacy of targeted antibody therapies for the treatment of cancer.
The Daria Gakalova Lab defines the functional role of epigenetics in transcriptional regulation of head and neck squamous cell carcinoma (HNSCC) progression. To evaluate the whole-genome distribution of various histone marks, her team is using chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-Seq) for primary tissues, a method recently developed by her lab. The research group of Daria Gaykalova was the first to demonstrate the cancer-specific distribution of H3K4me3 and H3K27ac marks and their role in cancer-related gene expression in HNSCC. The research showed that an aberrant chromatin alteration is a central event in carcinogenesis and that the therapeutic control of chromatin structure can prevent the primary of secondary cancerization. Further preliminary data suggest that the differential enrichment of these disease-specific histone marks and DNA methylation correlate with alternative splicing events (ASE) formation. For this project, Dr. Gaykalova... and her team employed a novel bioinformatical tool for the detection of cancer-specific ASEs. Through thorough functional validation of the individual ASEs, the lab demonstrated that each of them has a unique mechanism of malignant transformation of the cells. Due to high disease specificity, ASEs represent the perfect biomarkers of the neoantigens and have direct application to clinical practice. view more
The Johns Hopkins Head and Neck Cancer Tissue Bank enrolls patients and collects research specimens from Head and Neck Tumor patients, both cancerous and benign, with particular focus on Head and Neck Squamous Cell Cancer patients. It provides specimens to researchers both within the institution and outside.
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