Two Columbia Scientists Receive Hirschl Trust Research Awards

Iok In Christine Chio, PhD, and Oliver Clarke, PhD, both early-career investigators at Columbia University Vagelos College of Physicians and Surgeons, were awarded 2023 Hirschl Trust Research Awards by the Irma T. Hirschl Trust Research Scientist Program. Each investigator will receive a grant of $200,000 over five years to conduct novel high-risk, high-reward research that furthers new scientific knowledge, with the goal of improving patient care.

Since 1972, the Irma T. Hirschl Trust Research Scientist Program has provided support to junior biomedical research scientists at Columbia. VP&S is one of six academic medical centers in New York that receive funding from the Irma T. Hirschl Trust, which has supported more than 100 Hirschl Trust Research Scientists at VP&S.

Iok In Christine Chio, PhD

Assistant Professor of Genetics & Development (in the Institute for Cancer Genetics)

Chio studies pancreatic ductal adenocarcinoma (PDAC), which is the third leading cause of cancer death in the United States. The lethality of pancreatic cancer is due largely to the advanced disease stage at the time of diagnosis and its profound resistance to existing therapies.

Targeted therapy is a cornerstone of precision medicine and is the focus of the majority of anti-cancer drug development. However, in the context of pancreatic cancer, no chemical inhibitors exist for the most common KRAS mutations even though it is well established that the oncogenic KRAS promotes drug resistance.

Thus, a detailed understanding of the role of specific genetic lesions and their signaling surrogates in the initiation and progression of pancreatic cancer is critical to improving treatment efficacy and patient outcome for this disease. Using genetically engineered mouse models and ex vivo culture systems, Chio seeks to understand the basic mechanisms underlying PDAC biology so that vulnerabilities can be identified and tested for therapeutic intervention.

Oliver Clarke, PhD

Assistant Professor of Physiology & Cellular Biophysics (in Anesthesiology and the Irving Institute for Clinical and Translational Research)

Oliver Clarke’s lab conducts research on ankyrin complexes, a topic of outstanding physiological and pathophysiological significance. Ankyrins are giant spring-like proteins that modulate cellular shape and membrane curvature in red blood cells (erythrocytes), neurons, and myocytes. 

In erythrocytes, mutations in ankyrin complexes lead to several hereditary anemias in which the shape of the cell is dysregulated. Clarke uses single particle cryo-electron microscopy and cryo-electron tomography (cryoEM and cryoET, respectively) to understand how ankyrins interact with other elements of the cell to modulate membrane curvature. His work has important implications for both physiology and disease.

Clarke has already solved the initial structures using cryoEM; with the Hirschl Award he will now study the architecture of the ankyrin complex in native erythrocyte membranes using cryoET. This will allow him to probe not just the architecture of the isolated complex, but to characterize higher-order assemblies of ankyrin complexes and their interactions with the spectrin-actin cytoskeleton. This work is likely to lead to important insights into the mechanism by which the ankyrin complex modulates membrane curvature, and thereby controls cellular shape.