Kyle R. Siegel

Environmental toxicology and physiology & writing things

Developmental cardiac toxicity of metal mixtures


A growing body of epidemiological studies link how close a pregnant women lives to an oil and gas site with increased risk for congenital heart defects (CHDs) with the baby. There could be many reasons for these observations. However, exposure studies document increased levels of certain heavy metals on, and in, pregnant women who live closer to O&G sites than those who don't. Additionally, a strong body of work notes that O&G operations can contaminate nearby water bodies with these same metals, with increased levels persisting for weeks to months.
One of main projects is trying to experimentally assess if combinations of these highly enriched metals can negatively affect the development of the heart. I'm attacking these questions using biochemical, cellular, and animal models. 

I'm using H9c2 rat myoblasts, a cell line that, upon addition of retinoic acid (RA) and decreased nutrient levels, can differentiate into a cardiac muscle-like state. Currently, I'm testing if metal mixtures alter H9c2 physiology and differentiation capacity. I will also use human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to answer similar questions in a human cell model, as part of an Society of Toxicology-funded research experience with Dr. Laurie Svoboda (U. Michigan).

At the organism level, I'm testing if metal mixtures induce heart deformities in developmentally-exposed zebrafish, a powerful model for cardiotoxicity. Together, my data will begin to determine if there are links between metal exposures and developmental cardiotoxicity.