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Molecular Timekeepers: Converging Pathways in Circadian Control

Award Number: R35GM161590
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/10/2026
PERIOD OF PERFORMANCE END DATE: 01/31/2031

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Molecular Timekeepers: Converging Pathways in Circadian Control - PROJECT SUMMARY Circadian rhythms—daily cycles in physiology and behavior—were long thought to rely exclusively on genetic feedback loops. However, our laboratory has uncovered surprising evidence that these biological rhythms persist in contexts previously considered impossible, including red blood cells that lack nuclei and mice missing essential clock genes. These findings challenge conventional understanding of biological timekeeping and suggest the existence of fundamental timing mechanisms beyond traditional genetic control. Over the past five years, our work has established that metabolic and redox processes can sustain circadian rhythms independently of gene expression, developed novel tools to track these rhythms in real-time, and identified new regulatory factors that maintain rhythmicity even when core clock genes are absent. Building on these discoveries, our research program explores how cells and organisms maintain temporal organization through the integration of genetic and non-genetic mechanisms. We have engineered unique mouse models expressing fluorescent sensors that allow unprecedented visualization of cellular redox states alongside traditional clock gene activity. Using these tools, we investigate how metabolic cycles sustain timekeeping in cells lacking genetic rhythms, how newly discovered regulators coordinate different types of cellular rhythms, and how organisms maintain robust daily timing through redundant mechanisms. This work employs cutting-edge approaches including real-time imaging of single cells, genetic manipulation of model systems, and comprehensive molecular profiling. Our findings are reshaping understanding of biological timekeeping and have direct implications for human health. Disrupted circadian rhythms—whether from shift work, jet lag, or genetic variants—contribute to numerous diseases including metabolic disorders, cardiovascular disease, and cancer. By uncovering new mechanisms that cells use to maintain temporal organization, this research program aims to identify novel therapeutic strategies for treating circadian-related disorders. Our work thus addresses fundamental questions in biology while advancing the NIH's mission to reduce illness and improve human health.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $487,287 )
2026	2026	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	000	1	3/10/2026	NEW	$487,287
														Subtotal = $487,287

Grand Total All Awards = $487,287

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Molecular Timekeepers: Converging Pathways in Circadian Control

Award Number: R35GM161590

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/10/2026

PERIOD OF PERFORMANCE END DATE: 01/31/2031

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