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Three YSM Faculty Win Awards to Support Research in Aging, Geroscience

April 26, 2024

Three Yale School of Medicine professors are among the winners of the American Federation for Aging Research New Investigators Awards in Aging and Biology Geroscience Research. The winners each receive a three-year award totaling $375,000 to support their research into aging or biology geroscience.

AFAR announced the Second Cohort of the Hevolution/American Federation for Aging Research New Investigators Awardees in Aging and Biology Geroscience Research. The YSM faculty members are Caitlin Davis, PhD, Assistant Professor of Chemistry, Dan Jane-wit, MD, PhD, Associate Professor of Medicine (Cardiology) and Immunology, and Siyuan (Steven) Wang, PhD, Associate Professor of Genetics and Cell Biology. They are among 18 winners AFAR announced on April 26.

The Hevolution Foundation and AFAR provide the awards to junior investigators (MDs and/or PhDs) with at least three years of independent research who conduct research projects in basic biology of aging or geroscience. The program provides flexible support for research projects in basic biology of aging, as well as geroscience (projects that translate advances in basic research on aging biology from the laboratory to the clinic.)

The award will support Dr. Davis and her study on “Spatiotemporal Rewiring of Lipid Metabolism in Aging Tissues.” Dr. Davis is investigating biological hallmarks of aging in lipid metabolism. Aging is associated with a shift of metabolism towards lipogenesis. Therefore, understanding the dynamics of competing lipogenic pathways across the cell, their variations across cell types, and their responses to cellular stresses is crucial. However, measuring lipid metabolism inside the cell is not trivial. Using state-of-the-art infrared microscopy, this project investigates the spatial distribution, metabolic rates, and stress response of competing lipogenic pathways in aging fat and liver cells.

Dr. Jane-wit is studying “Complement Protein Aggregates in Age-Related Amyloidosis.” While the root causes of aging are unknown, protein aggregates are thought to have harmful effects. During aging, proteins become misfolded, forming aggregates that cause inflammation. Understanding which protein(s) become aggregated holds the promise of new therapies promoting healthy aging. Membrane attack complexes (MACs) are immune proteins long believed to contribute to aging via cell death. Work in Dr. Jane-wit’s laboratory surprisingly found that MAC proteins formed aggregates causing inflammation without cell death. Using innovative molecular tools and genetically-engineered mouse models, Dr. Jane-Wit will test a new concept that MAC aggregates promote age-related inflammation and decline in physiologic function.

Dr. Wang is studying, “Developing a High-Content Spatial Transcriptomic Screen Method to Discover Novel Regulators of Cell-Cell Interaction in the Native Senescent Microenvironment.” A fundamental question in the biology of aging revolves around understanding how different cell types and cell states change and interact to collectively contribute to the aging phenotype. This has been difficult to address as the aging process is not uniform across tissues and organs. In an aging tissue, a cell's position can be as pivotal as its inherent properties in shaping tissue function during aging. Recent breakthroughs in single-cell spatial omic technologies have significantly advanced our understanding of molecular and cellular organizations within tissues but cannot unveil direct functional mechanisms or causative factors. In this pioneering project, Dr. Wang aims to develop an in vivo genome-wide screening technology for identifying spatial transcriptome regulators in aging tissue, marking a new frontier in aging research. These identified regulators could be targeted to modify the spatial transcriptome associated with aging, fostering healthier aging by modulating spatial communication between relevant cell types.

Submitted by Terence P. Corcoran on April 26, 2024