Dr. Eli Hestermann

Environmental Toxicology, Cancer Pharmacology, and Endocrinology

My research is in two related fields: 1) the ways in which environmental pollutants such as PCBs, dioxins, and cigarette smoke are toxic to animals from fish to humans, and 2) the effects of drugs being used to prevent and treat breast cancer. This research is almost entirely at the level of the cell, and incorporates techniques from biochemistry, molecular biology and genomics. Students interested in environmental and human health research in cells have several projects to choose from.

Environmental Toxicology

Several organic pollutants, including such infamous chemicals as PCBs, Agent Orange, “dioxins” and the cancer-causing compounds in cigarette smoke, all act through a common pathway in the cell. These chemicals interact with a protein called the aryl hydrocarbon receptor (AHR), which acts in the nucleus to increase transcription of several genes. Most of these genes are for enzymes that metabolize the pollutants to forms that can be excreted from the body. Unfortunately, sometimes these enzymes convert the pollutants to more toxic forms.

My research involves studying the compounds that interact with the AHR to determine their toxicity in cells from several species, including fish, mice, rats, and humans. It’s true that chemicals that are harmful to lab rats aren’t always harmful to humans (and vice versa!), and I want to find out why. Also, there are some chemicals that interact with the AHR and actually prevent toxic effects, and I want to understand how they do this.

Cancer Pharmacology and Endocrinology

Most breast tumors depend on the hormone estrogen to grow and spread. This form of cancer is treated with drugs that bind to estrogen receptors (ER) in the cell and block the effects of estrogen. These drugs have side effects, such as increasing the risk of endometrial (uterine) cancer and causing hot flashes similar to those that women in menopause have. These side effects happen because estrogen acts in many different organs, including:

· bones - older women have weaker bones because their estrogen levels are lower

· the brain - estrogen may prevent Alzheimers

· the cardiovascular system - estrogen probably acts to lower blood pressure

· the reproductive system – estrogen is important in both the normal development and cancer progression in breasts, ovaries, and the uterus

I’m studying the effects of estrogen and the drugs that bind ER in these different cell types to find out what the shared and different properties are. This research will help us understand how estrogen acts in these tissues, how drugs interfere with estrogen, and how to design better drugs that block estrogen only in the tissue(s) that we want (like in breast cancer).

These two lines of research have converged. It turns out that AHR and ER can interact, and that AHR can affect ER in much the same way that certain drugs do. This complicates matters, but also gives us the opportunity to study the effects of chemicals that bind AHR in those tissues where ER is important.