Haiwei Gu

Title: Targeting Whole-body Fatty Acid Metabolism in Alzheimer’s Disease, with Special Interest in Lauric acid

Major goal: We hypothesize that whole-body metabolic reprogramming, including fatty acid metabolism, is profoundly involved in AD development and progression. The overall objective of this study (short-term goal) is to further collect validation and mechanistic data in human subjects, and to establish whether 3xTg mice reproduce abnormalities of fatty acid metabolism along the gut-liver-brain axis, making them useful for exploration of mechanisms and testing of potential treatments.

Title: Developmental PBDE exposure, gut microbiome, and diabetes

Major goal: We hypothesize that early life PBDE exposure causes acute and persistent dysbiosis, which upsets the balance between endogenous PXR activation (by indoles) vs. xenobiotic PXR activation (by PBDEs), leading to the delayed onset of diabetes. We seek to establish a causal relationship between developmental PBDE exposure, a change in gut microbiome, selective PXR modulation (sPXRm), and diabetes later in life using humanized PXR-transgenic (hPXR-TG) mice.

Title: Acceleration of Circulatory and Neurological Aging due to Wildfire Exposures

Major goal: The major goals of this project are to assess whether inhaled pollutants accelerate vascular neurological aging by augmentation of aging-related circulatory proteins and peptide fragments that: 1) compromise blood brain barrier integrity and alter microglial function; and 2) promote a reduced metabolic, senescent cellular phenotype that may be reversible with treatment of NAD+ boosting compounds.