Our research grants
Do Atmospheric Ultrafine Particles Lodge in the Brain and Cause Cognitive Decline Leading to Alzheimer's Disease Related Dementias?
RF1 NS130659 (Lein, DeCarli, and Kleeman) 09/20/2022 - 08/31/2027
The purpose of this grant is to test the hypothesis that ultra-fine particulate matter in polluted air promotes the onset and progression of Alzheimer’s disease (AD) and related dementias (ADRD) by determining whether (a) ultrafine particles are found in the brain of exposed individuals and whether this is associated with AD neuropathology (animal studies) or rate of cognitive decline (human studies) and (b) spatial-temporal distributions of ultrafine particles in northern California over the last 20+ years are associated with AD/ADRD.
UC Davis CounterACT Center of Excellence: Developing Therapeutic Strategies for Mitigating the Chronic Neurological Consequences of Acute Organophosphate Intoxication
U54 NS127758 Lein (PI) 09/01/2022 - 08/31/2027
Current medical countermeasures for acute organophosphate intoxication can prevent death, but are unable to fully protect against the longterm adverse neurological consequences (progressive brain injury, cognitive impairment, spontaneous recurrent seizures) unless administered within minutes of exposure, which is an unlikely scenario in the event of accidental, suicidal or terrorist-related exposures. The Center seeks to identify and develop novel disease-modifying therapeutic strategies that can be administered in hours to months after exposure to delay the onset and/or reduce the severity of chronic neurotoxic effects.
Does traffic-related air pollution accelerate the development of the metabolic syndrome by impairing the resolution of neurogenic inflammation?
R56 ES035798 (Taha, A.) 02/01/2025 - 01/31/2027
Exposure to traffic-related air pollution (TRAP) has been associated with an increased risk for metabolic disease; however, the mechanism(s) by which TRAP promotes or exacerbates this chronic disorder remain largely unknown. To address this data gap, we will leverage an established rat model of progressive metabolic disease to determine whether chronic exposure to TRAP, at human-relevant levels, accelerates metabolic disease development by impairing signaling pathways that normally function to resolve inflammation. These mechanistic studies are needed to corroborate human studies linking TRAP to increased risk for metabolic disease, and to inform regulatory and health interventions to reduce metabolic disease risk for individuals living, working or attending school near busy roadways.
Diversity Supplement to Molecular and Cellular Basis of PCB Developmental Neurotoxicity
R01 ES014901-13S1 (Lein and Lehmler) 08/29/2024 – 10/31/2026
The proposed supplement will investigate the contribution of extrahepatic metabolism by human and mouse cytochrome P450 enzymes influences neurotoxic outcomes in experimental animals exposed to LC-PCBs in the maternal diet throughout gestation and lactation. These outcomes are relevant to public health because they will provide data critically needed to assess the risk these emerging environmental contaminants pose to the developing brain and provide insights regarding strategies for mitigating this risk in vulnerable human populations.
Molecular and Cellular Basis of PCB Developmental Neurotoxicity
R01 ES014901 (Lein and Lehmler) 12/01/2020 – 10/31/2026
This research project quantifies the developmental neurotoxicity of lower-chlorinated polychlorinated biphenyls (LC-PCBs) found in the human gestational environment and investigates how metabolism by human cytochrome P450 enzymes influences neurotoxic outcomes in experimental animals exposed to LC-PCBs in the maternal diet throughout gestation and lactation.
Identifying lipid mediator pathways involved in neuronal survival and repair in Alzheimer's disease
R56 AG083336 (Taha, A.) 09/20/2024 - 08/31/2026
Alzheimer’s disease (AD) causes neuronal damage and loss over time, but underlying mechanisms remain unknown. The proposed research aims to close this knowledge gap by investigating how lipid pathways that control neuronal survival and repair are dysregulated in a transgenic rat model of AD, and by testing whether targeting defective lipid repair pathways in rats delays AD-related neuronal damage and loss. The proposed research will lay the scientific foundation for developing therapies that counteract neurodegeneration in AD by stimulating lipid-mediated brain repair pathways.
Diversity Supplement to UC Davis CounterACT Center of Excellence: The Role of the JAK/STAT Signaling Pathway in Chronic Neurological Effects of Acute Organophosphate Intoxication
U54 NS127758-S1 Lein (PI) 07/01/2023 - 06/30/2026
One goal of this supplement is to test the hypothesis that administering therapies that block the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway as adjuncts to standard of care will mitigate the long-term, adverse neurological consequences of acute OP intoxication. A second critical goal is to increase diversity of the scientific community with training on how to identify and develop more effective therapeutic strategies for reducing seizures and improving cognitive outcome in those patients who experience persistent drug-resistant disability following a chemical mass casualty event.
Diversity Supplement to UC Davis CounterACT Center of Excellence: Role of IL-1β in mediating the chronic adverse neurological effects of acute organophosphate intoxication
U54 NS127758-S2 Lein (PI) 07/01/2023 - 06/30/2026
One goal of this supplement is to test the hypothesis that administering therapies that antagonize interleukin-1β (IL-1β) signaling as adjuncts to standard of care will mitigate the long-term, adverse neurological consequences of acute OP intoxication. A second critical goal is to increase diversity of the scientific community with training on how to identify and develop more effective therapeutic strategies for reducing seizures and improving cognitive outcome in those patients who experience persistent drug-resistant disability following a chemical mass casualty event.
Traffic-Related Air Pollution Exacerbates AD-Relevant Phenotypes in a Genetically Susceptible Rat Model via Neuroinflammatory Mechanism(s)
RF1 AG074709 (Lein, Bein and Van Winkle) 05/01/2021 - 04/30/2026
The main objective of the project is to test the hypothesis that TRAP decreases the time to onset and/or increases severity of Alzheimer's disease-like phenotypes in genetically susceptible individuals via microglial cell activation secondary to lung inflammation.
UC Davis MIND Institute IDDRC
P50 HD103526 (Abbeduto) 07/01/2020-06/30/2025
The MIND Institute IDDRC supports ground-breaking studies of the early behavioral indicators of autism spectrum disorder (ASD); the role of immune disfunction in ASD risk; interactions between genetic susceptibilities and exposure to teratogens in risk for ASD and IDD; the range of phenotypes associated expansions in the FMR1 gene; structural and functional brain abnormalities underlying ASD, fragile X syndrome (FXS), chromosome 22q11.2 deletion syndrome (22q), and other IDD conditions.
UC Davis Environmental Health Science Core Center
P30 ES023513 (Hertz-Picciotto) 05/05/2015 – 03/31/2025
The overarching goal of the UC Davis Environmental Health Sciences Core Center is to expand the scope, innovation, and impact of EHS research so as to improve environmental public health in northern California, the Central Valley, and across the globe. Lein role: Leader, Career Development Program