Peter J Tontonoz
University of California-Los Angeles, CA·Physiology
Cholesterol and other fats (lipids) must be moved, stored and burned in the right amounts. When this goes wrong, it contributes to obesity, diabetes and heart disease.
- Fields
Physiology
Biochemistry
Medicine & Clinical Research
- Topics
cholesterol transport
nonvesicular lipid transport
Aster proteins
- Grants
- 4 known grants, through May 2030
What they work on
- Define how IL-22 from gut T cells suppresses fatty-acid uptake by intestinal cells, using genetic mouse models, chemical inhibitors and intestinal enteroids (lab-grown mini-intestines).
- Test the role of IL-22 receptor signaling in mature enterocytes for whole-body lipid balance using AlpiCreER; Il22ra1F/F mice, and test whether microbe-made AHR activators such as indole-3-acetate alter fat absorption.
- Identify cholesterol-binding proteins on blood-vessel endothelial cells, such as ICAM-1 and VCAM-1, using chemical biology under high-cholesterol and inflammatory conditions.
- Determine how accessible plasma-membrane cholesterol controls vascular inflammation and cardiovascular disease, using Aster-A loss-of-function endothelial cells and animal models.
- Identify proteins that work with Aster cholesterol transporters at ER–plasma membrane contact sites using proximity labeling, and test the roles of Snap23 and other partners in cells and animals.
- Determine how Aster-A phosphorylation triggered by cholesterol loading or bacterial LPS affects cholesterol transport and inflammation.
- Define how the ER protein Clstn3 keeps lipid droplets small and supports fat burning in brown fat, and test its effects in white fat cells and other tissues.
More about the research
This lab studies the cellular machinery that controls how lipids move through cells and the body, and how that machinery shapes metabolism and inflammation. A recurring focus is the Aster proteins, which the lab previously showed carry cholesterol from the plasma membrane (PM, the cell's outer membrane) to the endoplasmic reticulum (ER, an internal membrane network). Asters do this without packaging the cholesterol into vesicles, the small membrane bubbles cells often use for transport. Four projects apply this theme to the gut, blood vessels, basic cell biology and fat tissue.
Why it matters
These studies may point to new ways to treat high blood lipids (hyperlipidemia), obesity, diabetes, fat malabsorption and cardiovascular disease. Possible strategies include adjusting gut immune signaling through IL-22, calming cholesterol-driven inflammation in blood vessels, targeting Aster cholesterol transport, or increasing fat burning through Clstn3. People with metabolic and heart disease could eventually benefit, though the work is still at the stage of defining mechanisms.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
John Hancock
University of Texas Health Science Center at Houston, TX·Biochemistry
Test whether glycosphingolipids act as spatial organizers of the inner plasma membrane and ER-plasma membrane contact sites, using lipid biosensors and high-resolution imaging.
Bo Wang
University of Illinois Urbana-Champaign, IL·Physiology
Examine how SEC16B, a scaffold protein on the endoplasmic reticulum, regulates the formation of lipid droplets (fat-storage bodies) in liver cells, using cell-culture and in vivo experiments.
Trayambak Pathak
Louisiana State University Health Sciences Center-New Orleans, LA·Physiology·Early-career
Test whether calcium entry through Orai3 channels drives mitochondrial heat production in brown adipose tissue to limit fat buildup, by measuring mitochondrial metabolism in Orai3 knockout mice.
The school
University of California-Los Angeles: 84 labs on PI Pages, $1.9B a year on research, 803 research doctorates a year.
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