PIPages
Labs

Cetewayo Rashid

University of Kentucky, KY·Pharmacology

Flame retardants are added to furniture and other household goods to meet flammability rules, but some escape into indoor dust and end up inside people. One of them, the organophosphate flame retardant TDCPP (tris(1,3-dichloro-2-propyl) phosphate), is swallowed mainly through hand-to-mouth contact and broken down in the body to a chemical called BDCPP, which is detectable in the urine of about 90% of Americans.

Fields

Pharmacology

Physiology

Public Health & Epidemiology

Topics

flame retardants

organophosphate esters

endocrine disrupting chemicals

Grants
1 known grant, through Jun 2029

What they work on

  1. Test whether activation of PXR, a nuclear receptor that senses foreign chemicals, drives liver-specific insulin resistance in male mice fed diets containing the flame retardant TDCPP, using mice engineered to carry the human PXR gene.
  2. Determine whether PXR activation is required for metabolic disruption by comparing PXR-deficient mice and dietary exposure to BDCPP, the TDCPP breakdown product that does not activate PXR.
  3. Assess insulin action and insulin signaling directly in livers of male and female humanized PXR mice, using euglycemic clamp measurements and body composition analysis.
  4. Establish whether sex hormones underlie the male-specific effect by gonadectomizing male and female mice before TDCPP exposure and tracking body fat and glucose handling.
  5. Map the gene programs behind the sex difference by messenger RNA sequencing of livers from humanized PXR, PXR-deficient, and castrated mice exposed to TDCPP.

More about the research

National survey data tie higher urinary BDCPP to metabolic syndrome, a cluster of conditions including abdominal fat gain and high blood sugar, and the association shows up only in men. This project asks how a widespread indoor contaminant could disturb metabolism in males while females appear protected.

Why it matters

Nearly everyone in the U.S. carries traces of this flame retardant, and in men exposure tracks with metabolic syndrome, a precursor to type 2 diabetes. Pinpointing the receptor and hormonal steps involved could support screening strategies for flame retardants that meet fire-safety rules without disturbing metabolism, and may help explain why many hormone-disrupting chemicals affect men and women differently.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Mechanisms of Sex-specific Metabolic Disruption Caused by Organophosphate Flame Retardant Exposure

NIH · Jul 2024 – Jun 2029

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The school

University of Kentucky: 34 labs on PI Pages, $528M a year on research, 319 research doctorates a year.

More about University of Kentucky

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