Cells rely on an internal cleanup system to remove damaged components, including protein clumps associated with Alzheimer's and Parkinson's diseases. Understanding how that system is controlled could help researchers find more precise ways to clear harmful proteins while preserving other essential cellular functions. Hannah Lloyd, a postdoctoral associate in Cornell's Weill Institute for Cell and Molecular Biology, has received the 2026 Sam and Nancy Fleming Research Fellowship to investigate whether overlooked lipid attachments to proteins help regulate this process.

Lloyd does her research in the laboratory of Jeremy Baskin, professor of chemistry and chemical biology in the College of Arts & Sciences and faculty in the Weill Institute. For the Fleming Fellowship, she will explore a potentially overlooked mechanism controlling autophagy, the process used by cells to break down damaged components. Her research could deepen understanding of how cells remove the protein aggregates associated with neurodegenerative diseases, including Alzheimer's and Parkinson's.

"Hannah Lloyd's research asks a fundamental question about how cells keep themselves healthy, with potential implications for our understanding of neurodegenerative disease," said Brian Crane, the George W. and Grace L. Todd Professor in the Department of Chemistry and Chemical Biology in the College of Arts and Sciences, and director of the Weill Institute. "Her proposal to map the enzymes involved in autophagy is highly innovative and is a great example for how interdisciplinary science in the Weill Institute uses chemical and cell biological approaches to solve complex fundamental questions."

Lloyd's project, "The Missing Lipid Code," focuses on phosphatidylethanolamine, or PE, a lipid abundant in cellular membranes. When attached to a protein, PE can help anchor that protein to a membrane and influence its activity. This modification is known as PEylation.

Scientists have established that PEylation of a protein called LC3 is essential to autophagy, the destruction of damaged or redundant cellular components. LC3 helps cells build membrane compartments that enclose material destined for breakdown. Those compartments then fuse with lysosomes, where their contents are degraded.

"In order for cells and organisms to function properly, they need to be able to control what is inside of them," Lloyd said. "If you compare a cell to a city, sewers and garbage collection are important to the health of residents."

PE attachments on a small number of proteins beyond LC3 have been recently reported but are poorly understood, Lloyd said. Preliminary findings described in Lloyd's proposal suggest exciting new functions for this modification in autophagy. "PE is very common, and there are so many proteins working together to enable autophagy. If it is so important for this particular mechanism, what else is PE important for that we have not looked at yet?"

Lloyd plans to map these modifications, identify the mechanisms responsible for their attachment, and determine how individual modifications affect autophagy. She will combine chemical probes that make modified proteins easier to detect with computational modeling and genetic experiments.

"Protein degradation has to be tuned, and it has to be working properly," Lloyd said. "If autophagy is not functional, then proteins and protein aggregates can build up, and that is associated with neurodegenerative diseases. Even though different neurodegenerative diseases have different proteins that aggregate in different cells, they all have aggregate proteins that are not being removed."

After initial studies in standard laboratory cell models, she plans to investigate the modifications in cellular models of neurodegenerative disease.

Her proposal identifies a central challenge: stimulating autophagy to clear harmful protein aggregates without disrupting other cellular functions. Understanding the role of these lipid modifications could eventually reveal more selective ways to influence that process.

Baskin said that Lloyd had already established herself as a mentor and thought leader in the lab.

"Hannah's project in my lab centers on expanding our understanding of a fascinating, important, and oft-overlooked form of lipidation," Baskin said. "Because of its potential importance in membrane trafficking and dynamics, its intersection with lipid metabolism and neurodegenerative disease, and its leveraging of advanced chemical proteomics methods, Hannah's project is a great fit within the overall mission of the Weill Institute. She will benefit from interactions with several Weill research groups interested in these areas."

Lloyd joined Baskin's laboratory in January 2026 after completing her doctoral research with Christina Woo at Harvard University. She earned her doctorate in chemistry and chemical biology in February 2026, following bachelor's degrees in biochemistry and chemistry and a master's degree in biochemistry from Brandeis University.

Lloyd also brings experience teaching undergraduate and graduate courses, mentoring students and leading science outreach activities for children through Harvard Women in Chemistry.

"I am extremely grateful for the award, and for the committee for believing in my project. I am looking forward to continuing this research to try and fill in those missing details about how cells work, and what are the features that cause them to work."