BME7900 Seminar Series - José McFaline-Figueroa, PhD

Description

We welcome our next speaker, Dr. José McFaline-Figueroa. Dr. McFaline-Fiogueroa is an Assistant Professor in the Department of Biomedical Engineering at Columbia University.

Defining the Molecular Basis of the Response to Exposure Using Multiplex Single-cell Genomics

Abstract: The exposure of cancer cells to therapy induces complex changes that can alter clinical outcomes. Defining the molecular landscapes accompanying drug exposure can pre-emptively identify resistance mechanisms or inform new, more potent combinatorial strategies. To arrive at these maps of drug-induced molecular changes, we apply methods capable of profiling the response to many treatments at the resolution of single cells to account for heterogeneity in response. We developed “sci-Plex,” a method that combines sample multiplexing via nuclear “hashing” and the high-throughput of single-cell combinatorial indexing RNA-seq (sci-RNA-seq) to create a platform for multiplex single-cell chemical transcriptomics. More recently, we developed sci-Plex Gene-by-Environment (sci-Plex-GxE), a platform that extends sci-Plex to identify the genetic architecture that regulates drug-induced landscapes.

Here we present recent applications of sci-Plex and sci-Plex-GxE. We comprehensively profile the transcriptional response of cancer cells to the targeting of one of the most common oncogenic drivers in glioblastoma brain cancer via myriad chemical means, identifying heterogeneous responses of cells associated with the unique chemical properties of a compound. We probe known genetic dependencies to chemotherapy to develop strategies that prioritize genetic alterations with the largest effect on transcriptional drug responses. We highlight the ability of our approach for large-scale single-cell combined genetic and chemical screening by defining the contribution of the human protein kinome to the dynamic response of cancer cells to kinase-directed therapies. Overall, our approaches aim to arrive at actionable descriptions of the changes that underlie the response of tumor cells to therapy to inform future therapeutic interventions.

Bio: José L. McFaline-Figueroa received his bachelor’s degree in Chemistry from the University of Puerto Rico at Mayagüez and his Ph.D. in Cancer Cell Biology at the Department of Biology at MIT. His doctoral research focused on investigating the mechanisms by which glioblastoma brain cancer acquires resistance to the chemotherapeutic agent temozolomide. After completing his Ph.D., José joined the laboratory of Cole Trapnell at the University of Washington. As a post-doctoral fellow, he developed multiplex single-cell genomic tools to determine how genetic and/or chemical perturbation alters cellular response. In January 2021, José joined the Department of Biomedical Engineering at Columbia University. His laboratory applies and expands multiplex single-cell tools to define the molecular changes that cells undergo in response to therapy and how that responds depends on the genetics of a cell. José’s work has been recognized by various awards, including the NIH National Human Genome Research Institute’s Genomic Innovator Award and the NSF Career Award.