Our research projects
Active grants awarded to Pamela J. Lein:
UC Davis Environmental Health Science Core Center
P50 HD103526 (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
PCB-mediated Dysbiosis of the Gut Microbiome: A Missing Link in PCB-mediated Neurodevelopmental Disorders?
R01 ES031098 Cui, Lehmler (Contact) and Lein (MPI) 02/01/2020 – 11/30/2024
The goal of this project is to test the central hypothesis that dysbiosis of the gut microbiome associated with developmental expo-sure to varying doses of PCBs contributes to adverse neurodevelopmental outcomes.
PCB Epigenomic Brain & Behavior Lasting Effects Study (PEBBLES)
NIH/NIEHS R01 ES029213 (LaSalle/Lein/Schmidt) 06/01/18 - 05/31/23
This study leverages existing samples and behavioral outcome data from mice exposed perinatally to a mix of PCBs simulating the congener profile found in the serum of mothers in the MARBLES cohort with a new goal of identifying epigenetic placental biomarkers of PCB exposures and NDD risk. The unifying hypothesis is that genetic and PCB interactions can be detected as DNA methylation signatures in placenta to predict NDD.
Vascular Inflammation and Exosomes as Mediators in Aging and Dementia
NIH/NIA R01 AG056710 (Knowlton/Lein/Gelli) 04/01/18 - 03/31/23
The goal of this project is to test the hypothesis that senescent endothelial cells, which accumulate with aging, create a pro-inflammatory environment that adversely affects the blood brain barrier (BBB) and contribute to neuropathology implicated in age-associated dementias such as Alzheimer’s disease.
Novel Anticonvulsant and Neuroprotective Therapies for TETS and OP Intoxication
U54 NS079202 Lein (PI) 09/01/2012 - 08/31/2022
The unifying goal of the UC Davis CounterACT Center of Excellence is to identify improved medical countermeasures for treating acute intoxication with seizure-inducing chemical threat agents.
Inhibiting AD Inflammation with a Novel Class of Small Molecule PAI-1 Antagonists
R21 AG065908 Lein (Contact) and Gorin (MPI) 09/01/2019 - 08/31/2021
The objective of this project is to test the hypothesis that selectively killing microglia and astrocytes that express the serine protease inhibitor PAI-1 will reduce the neuro-inflammatory response and improve clearance of Aβ protein in the brain, thereby slowing cognitive decline in a rat model of Alzheimer’s.
Imaging Biomarkers of Early Synaptic Changes in a Preclinical Model of Alzheimer’s disease
R21 AG064599 Chaudhari (Contact) and Lein (MPI) 07/01/2019 – 06/30/2021
The goal is to test the hypothesis that in vivo imaging of synapse density is a predictive biomarker of AD pathology that precedes detection of amyloid deposition and neurofibrillary tangles by in vivo imaging.
Identifying Molecular Targets for the Proconvulsant Activity of TETS
R21 NS110647 Lein (Contact) and Wulff (MPI) 07/01/2019 - 06/30/2021
The goal of this project is to test the central hypothesis that α2β3γ2 receptors, which are far more abundant in the mammalian CNS than α6β3γ2 receptors, constitute the major molecular target of TETS and, based on the structural similarity between the two compounds, also of RDX.
Next Generation Neural Interfaces Based on Axonal Confinement in Micro-Channel Electrode Arrays
NIH/NIBIB R21 EB024635 (Seker) 04/01/18 - 03/31/21
The main hypothesis of this proposal is that the axons growing through micron scale channels can spontaneously form an electrical seal that isolates the axonal membrane patches to yield high signal-to-noise ratio (SNR) recording and immunity to mechanical vibrations or gliotic encapsulation of the electrodes. (Lein: Co-Investigator on grant)
Perinatal DDT Exposure Causes Insulin Resistance in Mice Through Impaired Thermogenesis
R01 ES024946 (La Merrill) 03/01/16 – 02/28/21
The overall objective of this proposal is to identify mechanism(s) by which environmentally relevant exposure to DDT during development increases risk of T2D in adulthood. Our central hypothesis is that developmental DDT exposure alters the epigenetic programming and/or sympathetic nervous system regulation of thermogenesis during early development, resulting in impaired thermogenesis throughout the life course. (Lein: Co-Investigator on grant)
Role of Excess Maternal Linoleic Acid Intake on Infant Neurodevelopment
R21 HD095391 (Taha) 02/01/2019 - 01/31/2021
The goal is to assess the impacts of dietary linoleic acid (LA) and its oxidized metabolites (OXLAMS) during pregnancy and lactation on child brain development and to identify specific metabolites responsible for possible adverse effects. (Lein: Co-Investigator on grant)
Molecular and Cellular Basis of PCB Developmental Neurotoxicity
R01 ES014901 Lein (Contact) and Pessah (MPI) 12/01/2008 – 11/30/2020
The main objective of this project is to test the hypothesis that developmental exposure to the MARBLES PCB mix disrupts neuronal connectivity via RyR-dependent effects on neuronal connectivity and the net outcome is influenced by heritable mutations that alter the fidelity of Ca2+ signals.