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Impact of Heat Stress on Drug Metabolizing Enzyme Expression and Function

Award Number: F31ES038410
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 11/01/2026
PERIOD OF PERFORMANCE END DATE: 10/31/2027

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Impact of Heat Stress on Drug Metabolizing Enzyme Expression and Function - Project Summary/Abstract Excessive heat (wet bulb globe temperature [WBGT] exceeding 32ºC termed “heat stress”) requires heat dissipation to maintain normal body temperature (37ºC). When heat stress exceeds heat dissipation, the concurrent rise in internal body temperatures above 38ºC (termed “heat strain”) or over 40ºC (termed “heat stroke”), results in more deaths than all other climate disasters combined. Within the United States, many areas regularly experience temperatures that surpass 40ºC annually, and many working conditions lead to a high number of individuals with little or no access to climate-control throughout the day. Additionally, many workers who labor in excessive heat for long periods are concurrently exposed to occupational and environmental chemicals. Toxicity from these compounds is largely determined by the absorption, distribution, metabolism, and excretion processes that determine the fate of chemicals within the body, where metabolism and transport determine exposure and toxicity. Interindividual variability that reduces metabolism and elimination of these chemicals results in increased susceptibility. Genetic variability is often seen as the mechanistic cause of susceptibility, but genetics is not the only factor in ADME function. Transient phenotypic conversion (phenoconversion) due to temporary environmental changes such as heat strain is often overlooked but can result in alterations in drug metabolizing enzyme function leading to the inability to properly eliminate toxicants. Whereas genetic variability identifies individuals who are inherently susceptible to toxicity, phenoconversion identifies conditions in which any individual can be at greater risk of toxicity. The investigative team has demonstrated numerous toxicologic examples of phenoconversion in both animal models and human participants with metabolic dysfunction-associated steatohepatitis (MASH), including pesticides, environmental contaminants, chemotherapeutics, and over-the-counter drugs. Preliminary data suggests that heat strain leads to profound alterations in drug metabolizing enzyme expression with the potential to increase toxicity. Exposures to chemicals considered safe in healthy individuals under controlled conditions may have significantly different outcomes in those same individuals following heat-induced phenoconversion. Thus, phenoconversion may provide a mechanistic basis for increased exposure and toxicity in workers and individuals exposed to excessive heat. The central hypothesis is that excessive heat alters the expression and function of major DMEs and transporters, thereby increasing the risk of toxicities in workers or individuals experiencing heat strain. I will test the hypothesis with the following aims. Aim 1: Identify the effects of acute and cyclical heat strain on the expression and function of genes important for detoxification through disposition in mice. Aim 2: Analyze the effects of heat strain on the toxicokinetics and toxicity of environmental and occupational chemicals in mice.


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 = $43,222 )
2026	2026	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Environmental Health	000	1	5/8/2026	NEW	$43,222
														Subtotal = $43,222

Grand Total All Awards = $43,222

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Impact of Heat Stress on Drug Metabolizing Enzyme Expression and Function

Award Number: F31ES038410

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 11/01/2026

PERIOD OF PERFORMANCE END DATE: 10/31/2027

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