José McFaline-Figueroa Wins NSF CAREER Award

Genomicist focuses on defining the molecular changes induced in aggressive cancer cells after they’ve been exposed to anti-cancer therapy and how those changes alter response to treatment

Mar 03 2022 | By Holly Evarts
José McFaline-Figueroa

José L. McFaline-Figueroa, assistant professor of biomedical engineering, has been recognized with a National Science Foundation (NSF) CAREER Award for his work on defining how cancer cells respond after exposure to anti-cancer therapy, and how that response depends on the genetic background of individual cancer cells. One of the NSF’s top honors given to early-career faculty, the three-year, $542,418 award will support his project, “Defining kinase-driven cellular response networks using single-cell genomics.”

One of the many difficulties in treating cancer is that tumors are heterogeneous--while a large population of cells will react one way to treatment, individual cells may react in another. It is thus critical to study tumors at the resolution of single cells to learn about mechanisms you might not see when examining a large group of cells.

Thanks to major advancements in the field, researchers can now isolate and characterize molecular components of a single cell within heterogeneous cell groups. McFaline-Figueroa develops and applies multiplex single-cell genomics tools that enable his group to probe the large combinatorial space between genes and exposures. His Chemical Genomics Laboratory then uses the functional atlases of cellular response obtained by their methods to identify more powerful treatment combinations to treat disease, especially cancer.

McFaline-Figueroa’s earlier work leveraged the throughput of novel single-cell genomic approaches for the multiplex assessment of the effect of genetic and chemical perturbations on gene expression programs. The NSF CAREER award will support his extending these tools to develop large-scale data-driven prediction of how individual genes contribute to the molecular changes that accompany cellular response.

The team plans to determine how protein kinases, master regulators of the cell, contribute to the dynamic molecular changes that cancer cells undergo in response to cytotoxic and genotoxic stress. The group will apply and broaden their methods for multiplex perturbation screens at single-cell resolution to probe the large interactions space between kinases and cellular stressors. The broader goal is to develop workflows to create functional molecular atlases with broad applications in various scientific fields, including therapeutic development and cellular engineering.

“We expect our methods will enable unprecedented insight into the regulatory networks that drive stress response and can be adapted to determine the genetic dependency of transcriptional phenotypes in a wide variety of experimental systems,” said McFaline-Figueroa, who is also an associate member of the Herbert and Florence Irving Institute for Cancer Dynamics and a member of the Herbert Irving Comprehensive Cancer Center. “This NSF CAREER award will support our group’s efforts to leverage these functional atlases of cellular response to arrive at novel treatments against cancer, with a particular focus on aggressive tumor types that frequently fail the current standard-of-care.”

McFaline-Figueroa also plans, as part of his NSF project, to work with high school students taking part in the NY Bioforce program and, in collaboration with the University of Puerto Rico, to develop a short course for graduate students at external institutions for the analysis of existing single-cell genomic datasets.