TOWARD PRECISION TOXICOLOGY
how does metabolism drive individual response to chemical exposures?
In the Hartman lab, we are interested in the broad question: if a population of people are exposed, why do only a few respond? We believe that a key factor in chemical exposure response is metabolism. Our research projects are centered around this central hypothesis.
HOW METABOLISM DRIVES EXPOSURE RESPONSE
One way that individuals differ in metabolism is through genetic and non-genetic differences in xenobiotic metabolism: this is how our body handles foreign chemicals, including drugs and pollutants. We study pathways we think are particularly important and understudied for inter-individual differences.
We also study how long-term diet and exercise habits cause fundamental shifts in the metabolic landscape (including how we handle glucose, fatty acids, and proteins) and how those big changes impact exposure to toxic chemicals.
from worms to humans
Our lab primarily works in the model organism Caenorhabditis elegans, a microscopic roundworm that has already contributed much to the field of biology and aging. C. elegans offers many advantages, including incredible genetic tools to dissect complicated metabolic pathways. We use worms to complement mammalian cell culture, rodent studies, and human studies which we do mainly in collaboration with other labs.
How Does Exercise Protect from Neurotoxicity?
In this project funded by a K99/R00 award from NIEHS, we have observed protection of dopaminergic neurons from chemical-induced damage after exercise. Now we are trying to understand how it works. Using our novel swimming exercise model in C. elegans, we are using unbiased appraoches to identify pathways that are required for this protection.
What is the role of mitochondrial CYP2E1 in acetaminophen and trichloroethylene toxicity?
CYP2E1, a mammalian enzyme expressed all over the body but in highest levels in liver, is absolutely required for drug toxicity from acetaminophen (brand name Tylenol) and pollutant toxicity from the drinking water contaminant trichloroethylene. However, the form of this enzyme that localizes to mitochondria may play the most important role, and we are studying how and why this happens.
What is the function of secreted MANF?
Mesencephalic astrocyte-derived neurotrophic factor, or MANF, is the only neurotrophic factor conserved from C. elegans to humans. We know that in the cells that make MANF, it acts as a regulator of the unfolded protein response in the endoplasmic reticulum. However, we also know that MANF gets secreted from cells. What happens after MANF leaves cells is a mystery that we intend to solve.