Texas A&M University System

Center for Environmental and Rural Health

Philip Mirkes, Ph.D.
pmirkes@cvm.tamu.edu
http://cerh.tamu.edu/

Project Description

The Center for Environmental and Rural Health (CERH) at Texas A&M University supports state-of-the-art research in the environmental health sciences and translates this knowledge into concepts and principles that can be easily adopted by rural communities in the State of Texas and beyond. The CERH provides administrative infrastructure and technical support to foster multidisciplinary research into basic mechanisms of environmental disease, from the gene to the organismal level, from molecules to social factors. The research activities of Center investigators are clustered into four major areas: Biostatistics and Community Health, Chemical Biology, Nutrition, and Reproductive and Developmental Biology. Each of these Research Cores consists of senior and junior investigators representing multiple departments and programs throughout the University. The funded research of these investigators is enhanced by six Facility Cores that provide resources to assist with experiments involving the use of Analytical, Biostatistics and Computational, Genomics and Bioinformatics, Imaging, Protein Chemistry, and Transgenic technologies. The Pilot Project Program supports up to 5 exploratory research projects per year related to the research focus of the Center. The Community Outreach and Education Program provides a mechanism for dissemination of important research findings of CERH investigators to rural communities, especially in the Lower Rio Grande Valley.

 Back to top

Program Highlights

Clay-Based Enterosorbent for Aflatoxins and Prevention of Liver Cancer

Figure 1. Space-filled

For the past 25 years, research in the laboratory of Dr. Timothy Phillips has focused on the development of innovative chemical strategies for the detection and detoxification of foodborne and environmental chemicals. In particular, the laboratory has employed molecular modeling techniques to characterize and design chemically diverse materials for the sorption and detoxification of aflatoxins, halogenated aromatic hydrocarbons, and diverse microbes. One aim of the laboratory has been to understand the surface chemistry and mechanisms involved in the interactions of aflatoxins with diverse clay and zeolitic minerals.  Dr. Phillips has shown that calcium montmorillonite clay can sorb aflatoxins, especially on interlayer surfaces (Figure 1), and this interaction results in decreased bioavailability and toxicity of these poisons from contaminated foods. From this basic research, Dr. Phillips has developed and patented a modified and refined clay (NSP), that has very high affinity and capacity for the aflatoxins.  Results from recent studies confirm the safety of NSP and that inclusion of this material at low levels in the diet significantly protects animals from aflatoxin-induced toxicity through preferential sorption in the gastrointestinal tract and subsequent excretion of the clay-aflatoxin complexes.  Additionally, NSP does not interfere with the utilization of important vitamins and micronutrients such as iron and zinc, nor does it induce any observable toxicity after long-term exposure. Based upon numerous studies of laboratory animals, Dr. Phillips and Dr. Jia-Sheng Wang (Texas Tech University) are currently conducting a study in Ghana, Africa, to monitor aflatoxin-exposed individuals and to determine the ability of NSP to reduce exposure to dietary aflatoxins based on biomarkers of exposure in blood and urine (Wang et al., 2005; Dash et al., 2007). For his research, Dr. Phillips has received numerous awards.

 Back to top

Development of New Receptor-based Anticancer Drugs

Figure 2.  Multiple modes of C-DIM anti-cancer

One of the themes underlying many of the research projects of CERH investigators is the role of diet in environmental toxicology. One example is the work of Dr. Stephen Safe, Deputy Director of the CERH and Director/member of the Environment & Cancer Research Core. Dr. Safe has maintained a long-term interest in the development of selective Ah receptor modulators (SAhRMs) for treating breast, endometrial, prostate, and pancreatic cancers. One class of SAhRMs is related to diindolylmethane (DIM), a metabolite formed from the phytochemical, indole-3-carbinol, which is widely found in cruciferous vegetables. Several synthetic DIM derivatives (C-DIMs) are highly effective anticancer agents; research on their mechanisms of action has resulted in identification of novel intracellular targets for these compounds (Figure 2). Several C-DIMs activate peroxisome proliferators-activated receptor g (PPARg), which is an important drug target that is overexpressed in many tumor types. In addition, several structural classes of PPARg-inactive C-DIMs also exhibited antitumorigenic/antiproliferative activity, and some of these analogs activate endoplasmic stress (ER) and interact with inner mitochondrial nucleotide transport proteins to induce apoptosis in cancer cells. Other subsets of C-DIMs activate several orphan receptors, and a recent report showed that specific c-DIMs can selectively activate nerve growth factor-induced-Ba [NGFI-Ba (Nur77)], a receptor that is also overexpressed in some cancers. Furthermore, ligand-dependent activation of Nur77 in cancer cells results in induction of TRAIL and apoptosis (Chintharlapalli et al., 2005; Cho et al., 2007).  In collaboration with Dr. Ashish Kamat, Director of the Surgical Fellow Program in the Department of Urology at M.D. Anderson Cancer Center, Dr. Safe has submitted a grant to study the role of Nur77 activators in treating bladder cancer.  Also being investigated is the role of these compounds in the treatment of cardiovascular disease, diabetes, and neurobehavioral diseases. Thus, Dr. Safe’s research has uncovered drugs that activate novel pathways which hold promise for cancer chemotherapy and other diseases.

 Back to top