RESEARCH INTERESTS

1. Wildlife as indicators for endocrine disruptors

A growing number of substances released into the environment have been identified as disruptors of critical, normal hormone-dependent mechanisms in humans and animals. These endocrine disruptors come from a variety of sources such as plants, pharmaceuticals, pesticides, environmental pollutants, and industry. The impact of these diverse compounds is far-reaching; from effects on human and wildlife health to contributing to wildlife population declines and resultant ecosystem imbalances. Particularly vulnerable are those life stages where considerable modeling or remodeling of existing body plans occur such as in embryonic development, metamorphosis, infancy, childhood and lactation. Thus, exposure to endocrine disruptors at any of these critical stages could result in permanent dysfunction, increased susceptibility to certain cancers and reproductive problems reaching as far as multiple generations. It is critical to have the appropriate tools in place to identify the existence of endocrine disruptors in water samples (where most will eventually end up) and to properly evaluate any endocrine disruptor risk in chemicals that are to be released into our environment. Amphibians, fish, marine mammals, bivalves, and other wildlife species are our sentinels. By developing and using a wide range of molecular approaches that include multi-species DNA arrays, quantitative real time PCR, proteomic, and metabolomic techniques, we are uncovering the mechanisms of action of potential endocrine disruptors and are gaining insight into how hormones function in different tissues and species.

2. Cellular mechanisms of hormone action

Hormones, such as thyroid hormone and estrogen, are important in regulating many cellular and developmental processes. The molecular mechanisms whereby these hormones work share common features and it is known that they influence each other. Additionally, a single hormone can initiate very different processes depending upon the cell and tissue context. For example, thyroid hormones can induce cell proliferation and programmed cell death. What determines how a cell "decides" what response to make is not well understood.

We use cutting edge molecular techniques, transcriptomics, proteomics, and metabolomics approaches to uncover the fundamental pathways that are involved in human cell lines and in the frog metamorphosis model.

A classic example of a single hormone affecting multiple pathways is the normal postembryonic development of the frog. A marked elevation of thyroid hormone (TH) levels triggers the rapid and dramatic metamorphosis of the aquatic tadpole to a terrestrial juvenile frog. The most obvious changes observed are the disappearance of the tail and the growth of the legs. This program focuses on understanding how the tail “knows” that it should die after receiving the triggering message from TH. We are particularly interested in the role that cell cycle regulating proteins, tumor suppressors, and phosphorylation may be involved in determining cellular outcome. Since frogs are vertebrates, the knowledge obtained by studying them can be easily applied to humans and, hence, will give us important clues in the control of cell death and cancer.

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Last Update, January 2011