Phone
(608) 262-8588Office Location
371B HF DeLuca Biochemistry Laboratories
433 Babcock Drive
Madison, WI 53706-1544
Education
B.S., Carroll College
Ph.D., University of Utah
Postdoctoral, University of Utah
- Stearoyl-CoA Desaturases regulate stem and progenitor cell metabolism and function in response to nutrient abundance
- Dietary isoleucine content modulates the metabolic and molecular response to a Western diet in mice
- ACAD10 and ACAD11 enable mammalian 4-hydroxy acid lipid catabolism
- Dietary lipids are largely deposited in skin and rapidly affect insulating properties
- Hepatic lipid remodeling in cold exposure uncovers direct regulation of bis(monoacylglycero)phosphate lipids by phospholipase A2 group XV
- Stearoyl-CoA desaturase 1 deficiency drives saturated lipid accumulation and increases liver and plasma acylcarnitines
- PLA2G15 is a BMP hydrolase and its targeting ameliorates lysosomal disease
- Cytosolic NADK is conditionally essential for folate-dependent nucleotide synthesis
- Phocaeicola vulgatus shapes the long-term growth dynamics and evolutionary adaptations of Clostridioides difficile
- Late-life protein or isoleucine restriction impacts physiological and molecular signatures of aging
As a postdoctoral fellow, I discovered that acylcarnitines are necessary for maintaining body temperature during cold exposure (Figure 1). Cold exposure triggers the release of free fatty acids from white adipocytes, which then go to the liver to where they are substrates for acylcarnitine production and secretion into circulation. These excess acylcarnitines are then taken up by the brown adipose tissue and used to fuel thermogenesis.
The Simcox laboratory will focus on two unanswered questions:
1) How are liver-produced lipids taken up & metabolized in brown adipocytes?
Brown adipocytes increase uptake of circulating lipids 12-fold during cold exposure, but the contribution of the various lipid species to thermogenesis remains elusive. We will use heavy isotope and fluorescently labeled lipids to identify lipid importers, assess metabolic pathways of uptake, and characterize the functional importance of various lipid species in isolated brown adipocytes (Figure 2).
2) How is hepatic lipid processing regulated in cold exposure?
Hepatic lipid processing is required for mice to maintain their body temperature in response to cold exposure. In untargeted lipidomic analysis we identified several hundred hepatic lipids that are altered in cold exposure and correlate with changes in circulating lipids. We will functionally characterize the role of these lipids in cold exposure and identify the transcriptional programs that regulate their production and clearance.