Four VP&S Physician-Scientists Named 2024 Gerstner Scholars

Four VP&S physician-scientists have been named 2024 Gerstner Scholars and will receive up to $300,000 to pursue promising research that has the potential to spark the development of new and better treatments for patients with kidney disease, cancer, and epilepsy:

• Andrew Beenken, assistant professor of medicine
• Kathleen Capaccione, assistant professor of radiology
• Ryan Moy, assistant professor of medicine 
• Tristan Sands, assistant professor of neurology and pediatrics 

The four new scholars represent the 16th cohort of scholars supported by the Louis V. Gerstner Jr. Scholars Program, which was created in 2008 to help exceptional early career physician-scientists pursue their ideas of improving patient care and become independent investigators.

Since 2014, the Gerstner Scholars Program also has awarded a Gerstner Merit Award, which provides a fourth year of funding, to a Gerstner Scholar who has made extraordinary progress in research, published work in high-impact scientific journals, secured or scored high on an NIH K or R grant application, and demonstrated exceptional growth as an academic biomedical investigator.

The 2024 Gerstner Merit Award recipient is Aaron Viny, assistant professor of medicine.

2024 Gerstner Scholars and Merit Awardee Projects

Andrew Beenken, MD, PhD

Project: “Structural regulation of megalin recycling in the proximal tubule”

Beenken’s goal is to advance understanding of kidney biology, in particular the structural basis for protein uptake and receptor recycling in the proximal tubule. Given that proteinuria contributes to the progression of chronic kidney disease, his work discovering the structural mechanisms underlying the production of a protein-free urine will have translational relevance to clinical medicine. Beenken aims to define structures of megalin at the pH of multiple endosomal compartments and correlate those structures with pH-dependent changes in Ca2+-coordination. Additionally, he seeks to define the structure of megalin in association with Receptor Associated Protein, its chaperone during biosynthesis. Through a comprehensive understanding of megalin’s structural transformations during recycling and biosynthesis, he plans to discover structural targets that could enable tuning the cell surface expression levels of this fast-recycling receptor. Such targets would open the possibility of either protecting the proximal tubule from toxins in disease states or increasing its receptivity to growth factors and nutrients during recovery from kidney injury.

Beenken earned his BS degree in chemistry from Yale University and his MD and PhD degrees from New York University.

Kathleen M. Capaccione, MD, PhD

Project: “Potentiating the effects of immune checkpoint inhibitor therapy with FAP targeted radiotherapy against non-small cell lung cancer”

Capaccione’s goal is to develop novel targeted therapies to treat lung cancer. As a graduate student, her work focused on the discovery and characterization of the Notch1 target Sox9 in non-small cell lung cancer. As a postdoctoral researcher, Capaccione extended her training in pharmacology to include radiopharmaceutical development and testing at the Columbia University PET Imaging and Research Center. These studies resulted in multiple high-impact publications and the preliminary data that form the basis for her Gerstner study. Using a murine model of inflammation, Capaccione’s work was the first to demonstrate that Granzyme B PET imaging can be used to visualize the innate immune response. Subsequently, she studied targeted radiotherapeutics as an anticancer strategy and optimized murine models of melanoma and lung cancer for testing radiopharmaceuticals. For her Gerstner project, she has assembled a team to investigate the mechanism by which targeted radiotherapy reduces tumor growth and how it interacts with immunotherapy.

Capaccione earned her BA degree in biology from New York University, her MD degree from Rutgers Robert Wood Johnson Medical School, and her PhD degree from Rutgers Graduate School of Biomedical Sciences.

Ryan Moy, MD, PhD

Project: “Elucidating targetable pathways to improve CLDN18.2 therapy in gastric cancer”

Moy leads a research program in stomach cancer therapeutics at VP&S and is PI on several clinical trials investigating novel therapeutics for gastric cancer. For his Gerstner project, he will define novel targets to augment therapies against Claudin 18.2, a new biomarker and drug target in gastric cancer that is highly expressed in approximately 30% to 40% of patients with gastric cancer tumors. While therapies targeting Claudin 18.2 are promising, pathways that regulate Claudin 18.2 expression and downstream signaling networks are poorly understood. He will leverage patient-derived organoids and mouse models to determine important druggable targets that act cooperatively with Claudin 18.2 targeting, which will provide new strategies that can be rapidly translated to clinical trials. His work is making headway toward new treatments for gastric cancer.

Moy earned his BS degree in molecular biophysics and biochemistry from Yale University and his MD and PhD degrees from the University of Pennsylvania.

Tristan Sands, MD, PhD

Project: “Convergence of neurodevelopmental channelopathies”

Sands is focused on improving the care of children with severe genetic epilepsy syndromes. As a PI within the Department of Neurology’s Center for Translational Research in Neurodevelopmental Disease, he works to devise novel therapies for devastating forms of epilepsy caused by rare gene mutations. His Gerstner research project brings to the laboratory clinical observations that have puzzled Sands since residency, having to do with the exquisite sensitivity of seizures caused by KCNQ2 and KCNQ3 loss-of-function disease to sodium channel blockade and phenotypic parallels between these voltage-gated potassium channel genes and voltage-gated sodium channel genes.

Sands earned his MD and PhD degrees from VP&S. He completed his child neurology residency at the University of California, San Francisco, where he developed his focus on genetic causes of epilepsy under the mentorship of Roberta Cilio. He completed epilepsy and clinical neurophysiology fellowships at Columbia under the tutelage of James Riviello.

2024 Gerstner Merit Awardee

Aaron Viny, MD, MS

Project: “Alterations in DNA methylation and chromatin structure as convergent pathogenic drivers in myelodysplastic syndrome”

Viny’s Gerstner project aims to show that chromatin structure and DNA methylation are both essential for gene regulatory networks in hematopoiesis. He will test the hypothesis that alterations in these genomic features represent a convergent mechanism to enforce transcriptional dysregulation in leukemia. Using novel mouse models and banked frozen bone marrow samples from MDS patients, he will illustrate the effects of DNA hypomethylation in normal and cohesin-deficient settings on transcriptional programs in hematopoiesis. These results will be juxtaposed with dynamic genome-wide DNA methylation in regulating CTCF binding and DNA loop formation in normal hematopoiesis. Using hypomethylating agents (HMA) as a chemical perturbagen, the effects of altered methylation on CTCF binding, DNA loops, and gene expression will be assessed. Viny’s goal is to develop a clinical assay to predict HMA response and develop a novel class of topologically guided therapeutics.

In addition to his appointment in the Department of Medicine, Viny has a faculty appointment in the Department of Genetics & Development and is a member of both the Columbia Stem Cell Initiative and the Cancer Genetics and Epigenetics Program at the Herbert Irving Comprehensive Cancer Center.