by Emily Overway
The Stanley Cohen Innovation Fund provides a yearly award to support innovative and groundbreaking research at Vanderbilt University. This year, after a competitive application process, Emily Hodges, PhD, assistant professor of Biochemistry, and Terunaga Nakagawa, MD, PhD, associate professor of Molecular Physiology and Biophysics, were named as the 2022 recipients.
Hodges’ proposed project investigates DNA methylation and how it influences cellular phenotypes.
Nakagawa’s proposal, an expansion on a project that was initially proposed and funded in 2021, aims to produce cryo-EM structures to map lipid interactions with membrane proteins and determine how these interactions impact the protein’s function.
The Stanley Cohen Innovation Fund began in 2019 and was named after the late Stanley Cohen, PhD, professor of Biochemistry, emeritus, and Nobel laureate. High-risk, high-reward projects funded through this program pay homage to Cohen and his seminal discoveries related to growth factor signaling. Cohen’s research provided a better understanding of embryonic and cancer development and laid the groundwork for the invention of anti-cancer drugs, some of which are still used today. The Cohen award is funded from an endowment established through the generosity of multiple donors. A very high bar has been set for funding so only one or two projects are funded following the School of Medicine-wide competition.
Hodges — decoding DNA methylation during cellulardifferentiation
DNA methylation is an epigenetic mark — a modification added to the DNA that does not change its sequence — that typically turns a gene off. Dysfunctional DNA methylation can have a massive impact on cell function and on cells’ ability to differentiate into specific cell types during development, ultimately leading to developmental and aging defects and diseases like cancer. Despite this, its specific role in regulating these processes has been elusive.
“While textbooks define methylation’s role as a repressor of transcription, we are learning that this definition does not really tell the whole story,” Hodges said.
Hodges’ project will provide a deeper understanding of DNA methylation by investigating its presence throughout different stages of cellular differentiation and different regions of the genome.
Her lab will monitor methylation patterns on chromatin, along with the accessibility of the chromatin, under conditions of dynamic gene regulation in both single cells and across different cellular systems. Through this work, they hope to define the role of DNA methylation in determining cellular identity and function.
“The Stanley Cohen award celebrates curiosity-driven, innovative projects that challenge existing paradigms,” Hodges said. “Opportunities to receive funding for these higher-risk projects is critical for driving new discoveries and forging new areas of research.”
Nakagawa — biological significance of lipids associated with membrane proteins
Despite being a critical component of all cells, the function of lipids remains incompletely defined. Lipids are of major biological significance as they alter the activity of many membrane proteins.
This is highlighted by the fact that activities reported for proteins isolated from the membrane are frequently at odds with activities reported for those proteins when they are embedded in the membrane.
Nakagawa’s project uses cryo-electron microscopy to investigate the interactions between lipids and membrane proteins. The proposal centers on investigating the interactions between lipids and a critical neural receptor, but the methodologies used could be widely applied. Nakagawa’s lab will test the hypothesis that each membrane protein requires interaction with an optimal set of lipids for proper physiological function and regulation.
“The Stanley Cohen Innovation Fund supports risk-taking projects that are difficult to receive funding for through traditional, external funding mechanisms,” Nakagawa said. “It is an excellent funding mechanism to foster high quality science that requires risk taking.”
The Cohen fund plays a key role in providing faculty with the opportunity to pursue groundbreaking research and have a major impact on improving human health and disease.