Izumi Maezawa
University of California-Davis, CA·Neuroscience
Fats and fat-derived signaling molecules help control inflammation in the brain. When that control fails, it may contribute to Alzheimer's disease and to brain injury in newborns.
- Fields
Neuroscience
Pharmacology
Biochemistry
- Topics
Alzheimer's disease
microglia
neuroinflammation
- Grants
- 3 known grants, through May 2031
What they work on
- Map lipid and metabolite changes in single microglia near amyloid plaques, blood vessels and lipid droplet-rich ACSL1-positive cells across human Alzheimer's progression using MALDI mass spectrometry imaging with multiplexed immunofluorescence.
- Test whether β-hydroxybutyrate, a major ketone body produced in therapeutic ketosis, reduces microglial metabolic and lipid dysfunction in Alzheimer's model mice.
- Delete the lipid enzyme ACSL1 specifically in microglia to test whether disrupted lipid metabolism causes microglial dysfunction, and whether toxic lipids pass from these microglia to nearby neurons.
- Delete soluble epoxide hydrolase only in microglia or liver cells of APP-PS1 Alzheimer's mice and use transcriptomic and lipidomic analyses of liver, brain and plasma lipoproteins to find protective mechanisms.
- Compare brain bioactive lipids and plasma lipoprotein lipid makeup between Alzheimer's patients and non-demented controls across APOE genotypes.
- Test whether amyloid-β oligomers push human iPS cell-derived microglia toward inflammation by lowering anti-inflammatory epoxy fatty acids, and whether APOE genotype changes this effect.
- Test whether sEH gene knockout or the sEH inhibitor TPPU protects newborn mice from inflammation-sensitized hypoxic-ischemic brain injury, and profile liver, plasma and brain lipids to map a liver-to-brain protective route.
More about the research
A common thread across these projects is lipid metabolism, especially in microglia, the brain's resident immune cells. The work also asks whether the liver, by shaping which lipids the blood carries, helps protect the brain. Two projects target soluble epoxide hydrolase (sEH), an enzyme that quickly breaks down anti-inflammatory epoxy fatty acids (EpFAs) into molecules that promote inflammation. A third project maps the chemistry of individual microglia directly in brain tissue.
Why it matters
Alzheimer's disease and perinatal brain injury both lack effective protective treatments. This work could identify soluble epoxide hydrolase as a drug target to protect the brains of high-risk premature infants and people with Alzheimer's disease, and could reveal lipid features of harmful microglia, including responses to therapeutic ketosis, that point to new Alzheimer's treatment targets.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Tae-Wan Kim
Columbia University, NY·Neuroscience
Determine how the neuronal signal SEMA3A promotes β-amyloid uptake and a disease-associated microglia gene profile in human iPSC-derived microglia (iMGLs), independently of the TREM2 receptor.
Ruixuan Gao
University of Illinois Chicago, IL·Chemistry·Early-career
Develop a tissue polymerization and expansion pipeline that anchors natural lipids to a swellable polymer gel, allowing MALDI mass spectrometry imaging of lipids at subcellular resolution on conventional instruments.
Ying Xu
Rutgers University-New Brunswick, NJ·Neuroscience
Test whether removing PDE2A, an enzyme that breaks down the messengers cAMP and cGMP, from the forebrain protects against pathology and memory deficits, by crossing conditional knockout mice with Alzheimer's transgenic mouse models.
The school
University of California-Davis: 49 labs on PI Pages, $1.0B a year on research, 647 research doctorates a year.
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