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Identifying how time of treatment modulates cancer-related inflammation and cognitive dysfunction

Award Number: K99CA315592
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Identifying how time of treatment modulates cancer-related inflammation and cognitive dysfunction - Chemotherapy and immunotherapy cancer treatments have improved cancer mortality but can cause debilitating side effects such as cognitive dysfunction that can decrease quality of life. Growing evidence indicates treatmentinduced cognitive dysfunction is mediated by increased peripheral inflammation communicated to the brain, causing neuroinflammation, which is propagated by the resident macrophage of the central nervous system, microglia. Both peripheral and central inflammation are highly regulated by circadian rhythms. For example, immune cell reactivity is highest during the early light cycle (i.e., morning) in both humans and rodents. Thus, leveraging cancer treatment time of day (ToD), termed “chronotherapy”, could be a viable strategy to mitigate side effects of treatment my abating treatment-induced inflammation. My preliminary data demonstrates that breast cancer patients have increased circulating pro-inflammatory mediators associated with worse selfreported cognitive deficits when most chemotherapy infusions occur before noon compared to afternoon. In a chemotherapy mouse model, morning treatment increased markers of neuroinflammation and cognitive deficits compared to night. I hypothesize that circadian control of immune responses causes morning treatment to exacerbate neuroinflammation, increasing treatment-induced cognitive dysfunction. My goal is to identify targetable mechanisms that drive ToD differences in cancer treatment to improve patient outcomes. Aim 1 (K99) will determine the extent to which chemotherapy ToD modulates the relationship between inflammation and cognitive deficits in breast cancer patients by investigating the transcriptome of peripheral immune cells associated with circulating inflammation and cognitive function. Aim 2 (K99) will determine the role of microglia in chemotherapy ToD-induced cognitive deficits in a mammary tumor mouse model. Specifically, I will investigate if immune and behavioral responses of chemotherapy ToD are dependent on circadian-regulated microglial functions by ablating microglia circadian rhythms and interrogating microglia-neuron interactions ex vivo. Aim 3 (R00) will determine how ToD modulates immunotherapy cognitive side effects in lung cancer patients and a lung cancer mouse model. This will be achieved by retrospectively analyzing lung cancer patients that received immune checkpoint inhibitors, relating infusion timing to inflammatory mediators, cognitive function, and immunerelated adverse events. I will then measure how immunotherapy ToD influences peripheral and central inflammatory responses related to cognitive behavior in a lung tumor mouse model. Animal models will be used in conjunction with human datasets to investigate brain-specific mechanisms of CRCI, which would not be possible in humans. My mentorship team of experts in clinical, cancer, and circadian rhythms research will ensure I receive training in high level techniques and develop professional skills necessary to become a successful independent investigator. This award will allow me to establish a unique research program that investigates novel approaches to improve cancer survivors’ quality of life without compromising treatment efficacy.


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 = $127,282 )
2026	2026	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Research Manpower	000	1	8/12/2026	NEW	$127,282
														Subtotal = $127,282

Grand Total All Awards = $127,282

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Identifying how time of treatment modulates cancer-related inflammation and cognitive dysfunction

Award Number: K99CA315592

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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