Jorge S. Reis-Filho: Research Overview

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Our multidisciplinary team focuses on two main areas, namely intra-tumor genetic heterogeneity, its causes, consequences and therapeutic vulnerabilities, and on the identification of novel genotypic-phenotypic correlations in human cancers, by focusing on extremes of phenotype.

We have developed wet lab and computational approaches to address fundamental questions on the impact of specific types of DNA repair defects in cancer, their impact on cancer genomes and how to explore the therapeutic vulnerabilities caused by these DNA repair defects. In particular, we are seeking to define the impact of homologous recombination (HR) DNA repair deficiency (HRD) in human cancers, including a characterization of the basis of HRD, the impact of mutations affecting different components of the HR pathway and the therapeutic strategies to target HRD above and beyond PARP inhibitors. We have developed novel methods for single cell DNA sequencing that can be applicable to formalin-fixed paraffin-embedded samples, as well as innovative approaches for the sequencing of circulating cell-free DNA (cfDNA) to characterize the entire repertoire of genetic alterations in metastatic cancer patients.

Our laboratory has a track record in the identification of novel genotypic-phenotypic correlations in rare tumors. Following the hypothesis that rare tumor types would constitute extremes of phenotype, we have employed sequencing approaches that resulted in the identification and functional characterization of novel pathognomonic genetic alterations (e.g. PRKD1 E710D hotspot mutations), novel cancer genes (e.g. ATP6AP1 and ATP6AP2) and new combinations of genetic alterations resulting in specific phenotypes in the context of breast cancer (e.g. HRAS Q61 hotspot mutations in conjunction with PIK3CA or PIK3R1 mutations in adenomyoepitheliomas of the breast).