Student Information Training Programs Research Centers

Pharmacology & Toxicology

Toxicology Training Program - Areas of Study

John H. Richburg, Professor of Pharmacology & Toxicology; Head, Division of Pharmacology & Toxicology; The University of Texas at Austin; Austin, Texas 78712; (T) (512) 471-4736 (FAX) 471-5002; email:
Director, NIEHS Toxicology Training Grant
Research is targeted to decipher the cellular and molecular signals instigated in the testis that are responsible for the balance between survival and apoptosis of testicular germ cells. Although many studies in humans have associated alterations in the incidence of germ cell apoptosis with conditions of abnormal spermatogenesis and male infertility, the cellular processes that regulate germ cell apoptosis in the testis remain poorly characterized. In particular, research has focused on the regulation of germ cell apoptosis as a result of environmental toxicant-induced Sertoli cell injury. Since analogous decreases in Sertoli cell support and increases in germ cell apoptosis occur during early postnatal testis development, revealing the mechanisms by which germ cell apoptosis is regulated will enhance understanding of both the physiological importance of this process during distinctive periods of testicular development as well as provide insights into cellular targets of environmental toxicants and possible mechanisms of infertility. It is anticipated that the mechanistic insights provided from this work will be useful for predicting and preventing human reproductive health risks to chemicals, such as the phthalates, found ubiquitously in the environment. These studies are currently funded via NIEHS R01 funding. Collaboration with Drs. Bratton, Gore, and Finnell.

Shawn Bratton, Associate Professor of Molecular Carcinogenesis, The University of Texas, M.D. Anderson Cancer Center; Science Park - Research Division, P.O. Box 389, Smithville, Texas 78957; (T) (512 237-9461; email:
Research is centered on cellular mechanisms of toxicant-induced apoptosis (cell suicide) and autophagy (self-cannibalism). There are four main areas of research in the lab: 1) study of the Apaf-1 apoptosome, a large caspase-activating complex activated during stress induced apoptosis; 2) study of inhibitor of apoptosis (IAP) proteins that suppress apoptosis through inhibition of caspases; 3) study of the novel mechanisms of heat shock-induced apoptosis; and 4) study of the basic mechanisms of autophagy and its role in prostate cancer. Each of these areas has relevance to toxicant-induced tissue injury and tumor development after environmental toxicant exposure. For the first project, Dr. Bratton is currently collaborating with Dr. Richburg to uncover the role(s) of caspase-9 in the development and sensitivity of the testis to toxicants using a novel caspase-9 knock-in mouse model.

David Crews, Ashbel Smith Professor of Zoology and Psychology, The University of Texas at Austin; Austin, Texas 78712; (T) (512) 471-1113 (FAX) (512) 471-6078; email: Life is a combination of exposures inherited from ancestors due to heritable epigenetic modifications to DNA in germ cells (transgenerational), together with exposures experienced during the individual’s own lifetime (body burden) that cause molecular epigenetic changes to that individual. These processes are an underappreciated force in driving evolutionary change. The challenge is how to model the cumulative and progressive changes across generations and within lifespans. The Crews lab employs multigenerational exposures to sequential environmental toxicants, each known to perturb hormones, brain and behavior. This experimental model investigates interactions of ancestral and immediate epigenetic modifications, factors that have never been studied together. A new NIEHS R01 grant with Dr. Gore has been awarded to support these studies.

John DiGiovanni, Professor of Pharmacology & Toxicology, The University of Texas at Austin; Division of Pharmacology & Toxicology; Austin, Texas 78712; (T) (512) 495-4726; email:
Research is currently focused in three main areas. First, studies are ongoing to identify new mechanisms and targets for prevention of epithelial cancers caused by environmental agents. These studies use a well-established mouse model for both chemical- and UV-induced skin carcinogenesis. The environmental chemicals used in this mouse model include the ubiquitous polycyclic aromatic hydrocarbons (PAHs). These studies are focused on understanding important growth factor (e,g, Stats and Akt/mTOR) and inflammation (NFkB) signaling pathways involved in cancer development by these environmental agents. Another major aspect of research in this area is focused on developing new animal models for understanding mechanisms of environmental carcinogenesis. The second area of research interest involves studying the effects of dietary energy balance, including both obesity and calorie restriction on epithelial carcinogenesis. These studies are leading to the discovery of naturally occurring phytochemicals as potential calorie restriction mimetics for cancer prevention. Finally, in other ongoing projects, the DiGiovanni group is mapping and identifying novel cancer susceptibility genes that regulate susceptibility to environmental carcinogenesis. These studies use mouse genetics to first identify candidate susceptibility genes and then these genes are analyzed in human populations for their role in particular cancers with a strong link to environmental exposures. These studies are supported by grants from NIEHS. Collaboration with Drs. Vasquez and Mills.

Richard H. Finnell, Professor of Nutritional Sciences, Professor of Chemistry and Biochemistry; The University of Texas at Austin; Austin, Texas 78712; Director, Genomic Medicine at Dell Children's Medical Center; (T) (512) 495-3001 (FAX) 495-4805; email:
Research in the Finnell Laboratory utilizes three primary approaches to investigate gene-environment interactions as they relate to environmentally induced birth defects. These approaches include: embryonic stem cells (including the development of iPS cell lines from patients with genetic disorders), development of genetically modified mouse models of environmentally mediated diseases, and human clinical and molecular epidemiology studies. Using state of the art genomic and epigenomic approaches to the causes underlying complex congenital defects in China and in the US, they hope to identify novel targets for intervention. This work is supported by two NIEHS grants. They are also utilizing murine embryonic stem cells with gene inactivation to develop high information content-high throughput screens for environmental toxicants that can compromise reproductive and endocrine endpoints. This work is supported by a grant from the US EPA. A collaboration to evaluate the developmental abnormalities of mice deficient in the gene for the E3 ligase Itch is ongoing in collaboration with Dr. Richburg.

Andrea C. Gore, Professor of Pharmacology & Toxicology, The University of Texas at Austin; Division of Pharmacology & Toxicology; Austin, Texas 78712; (T) (512) 471-3669 (FAX) 471-5002; email:
Dr. Gore's current research focuses on the effects of prenatal exposure to environmental endocrine disrupting chemicals in reproductive development, adult reproductive physiology, and behavior, including transgenerational effects. Specifically, experiments examine why the brain may be a primary target of EDCs, and their disruption of the neural mechanisms of reproductive development and puberty. New studies are also deciphering whether EDCs have transgenerational effects on gene expression in neuroendocrine cells. These studies may help in developing interventions to protect against environmental factors that may perturb normal reproductive development. These studies are funded by an active NIEHS R01 grant and a new NIEHS R01 grant in collaboration with Dr. Crews.

Seongmin Lee, Assistant Professor of Medicinal Chemistry, The University of Texas at Austin, Austin, Texas 78712; (T) (512) 471-1785 (FAX) 232-2606; email:
Research focuses on elucidating the mutagenesis mechanisms of halogenated DNA lesions that can be generated by endogenous and exogenous chlorinating agents such as hypochlorous acid and hypobromous acid. Hypochlorous acid is widely used as a bleaching agent and a disinfectant, and is also generated in activated neutrophils to kill pathogens during inflammation. The chronic exposure to hypohalous acids has been implicated in mutagenesis and cancer development, yet its molecular mechanism is poorly understood. The long-term research goal of the Lee lab is to elucidate the effects of 8-halogenated guanine, the major DNA lesions formed by hypohalous acids, on biological processes such as DNA repair, DNA replication, transcription, DNA methylation, epigenetic mechanisms, and tumorigenesis. Currently, the Lee lab utilizes combined tools of synthetic organic chemistry, biochemistry, and structural biology to clarify the structural basis for halogenated guanine-mediated mutagenesis and evaluate the effects of halogenated guanine in CpG dinucleotides on epigenetic mechanisms. Studies are funded by NIEHS R21 grant.

Kevin McBride,Assistant Professor of Molecular Carcinogenesis, The University of Texas, M.D. Anderson Cancer Center; Science Park, 1808 Park Road 1C, Smithville, Texas 78957; (T) (512) 237-9338; email:
Investigations in the McBride lab are focused on revealing environmental and pharmacological conditions that induce or regulate the DNA mutator enzyme, activation-induced cytidine deaminase (AID); a DNA cytidine deaminase that initiates mutation and double stranded DNA breaks. In B lymphocytes, AID action diversifies antibody genes and is critical for proper immune function. However, AID is a significant threat to genome integrity and therefore must be strictly regulated. This is known to occur at both the transcriptional and post-translational modification level. Although normally confined to B cells, “inappropriate” expression in non-immune cells has been observed under pathological conditions often associated with cancer. These include exposure to radiation, inflammation, and certain hormones such as estrogens. Due to its mutator activity, AID provides a causative mechanism of how these agents contribute to carcinogenesis. The lab is utilizing mouse models, expression indicator systems and single cell analysis to study: 1) Environmental conditions that contribution to carcinogenesis through AID expression; 2) Mechanisms that regulate AID activity and pharmacological agents that disrupt regulation; 3) The resulting chromosome rearrangement and somatic hypermutation at the single cell level. The ultimate goal of these studies is to identify where AID contributes to pathology and identify means to mitigate it. Collaborating with the Bedford lab regarding post-translational modification of AID.

Edward Mills, Associate Professor of Pharmacology & Toxicology, The University of Texas at Austin; Division of Pharmacology & Toxicology; Austin, Texas 78712; (T) (512) 471-6699 (FAX) (512) 471-5002; email:
The goal of the Mills laboratory is to understand molecular mechanisms regulating energy balance and how these processes can be influenced by diet and environmental agents to contribute to disease. At the heart of their investigations are mitochondria – in particular the mitochondrial uncoupling proteins (UCPs). UCPs control the efficiency of oxidative phosphorylation by regulating proton flux across the inner mitochondrial membrane. In humans, the physiologic functions of the UCP homologs (UCP2, UCP3) have not been established, and for all UCPs, the mechanism of proton transfer has not been elucidated. Using genetically modified knockout and tissue targeted transgenic mice, the lab has shown that UCP3 is a potent thermoregulatory protein that is the toxicologic target activator of amphetamine hyperthermia. On the other hand, when UCP3 is specifically expressed in skin, it dramatically blocks skin carcinogenesis induced by tumor initiating and promoting toxicants. These findings are being extended to define the anatomy and mechanisms of UCP3-dependent thermogenesis and proton transport, and to understand the basis for UCP3’s potent anticancer properties in chemical, genetic, and environmental (ultraviolet light) models. These studies are broadly implicated in relationships between metabolism and age related diseases, obesity, and cancer. Collaborations with Drs. DiGiovanni and Wright.

Somshuvra Mukhopadhyay, Assistant Professor of Pharmacology & Toxicology, The University of Texas at Austin; Division of Pharmacology & Toxicology; Austin, Texas 78712; (T) (512) 232-8200 (FAX) (512) 471-5002; email:
Manganese is an essential metal but environmental and occupational over-exposure to Mn leads to the development of a Parkinsonian syndrome that has no treatment. Despite the clinical significance, mechanisms involved in the regulation of manganese homeostasis and detoxification in mammalian cells are poorly understood. Research to date has focused on the role of Mn influx but the identified influx transporters are neither specific for Mn nor regulated by alterations in cellular Mn levels. In contrast, the role of efflux of cytosolic Mn has been largely overlooked, although metal efflux is well recognized as a regulatory mechanism for maintaining cellular metal homeostasis and deficits in efflux are associated with cellular metal accumulation and toxicity. Significantly, the Mukhopadyhyay lab recently identified transport of Mn into the Golgi followed by secretion to be the primary route of Mn efflux in mammalian cells and further demonstrated that increasing Golgi Mn uptake enhances Mn efflux and protects against toxicity, while blocking Golgi Mn uptake has the opposite effect. Based on this, the goal is to elucidate mechanisms of Mn efflux via the Golgi so as to better understand the role of this fundamental process in Mn homeostasis and in the pathobiology of Mn-induced neurotoxicity. These studies are funded by a NIEHS R00 award.

Dean Tang, Professor of Experimental Carcinogenesis, The University of Texas, M. D. Anderson Cancer Center; Science Park - Research Division, P. O. Box 389, Smithville, Texas 78957; (T) (512) 237-9575 (FAX) (512) 237-2475; email:
Investigations are targeted to understand the molecular mechanisms regulating environmental toxicant-induced cell death via apoptosis, with a specific emphasis on the role of mitochondria in both the intrinsic and extrinsic pathways of cell death. One new project focuses on the pro-survival signaling mechanisms in cancer stem cells (CSCs) and their progeny. The emphasis is put on the intrinsic death pathway involving apoptosome assembly and caspase activation in several populations of well-characterized CSC populations when exposed to radiation or challenged by pro-oxidants, chemotherapeutic drugs, or endocrine disruptors. Another new project aims to elucidate how environmental toxicants and carcinogens as well as endocrine disruptors turn normal stem cells into CSCs and initiate tumor development. The ultimate goal of these projects is to uncover the unique properties of CSCs and to understand the influence of environmental agents on modifying pro-survival/pro-death signaling pathways. Collaboration with Dr. Bratton and John DiGiovanni.

Peter Thomas, Professor of Marine Science & Integrative Biology, The University of Texas at Austin; Marine Science Institute; Port Aransas, Texas 78373; (T) (361) 749-6768; email:
Research is aimed to decipher the mechanisms of interference with reproductive endocrine function by environmental chemicals and hypoxia, primarily using fish as vertebrate models. An emphasis is on the structure, function, and evolution of two new classes of sex steroid receptors for progestins and estrogens that were recently discovered in fish and other vertebrates, including humans. The novel receptors are structurally unrelated to nuclear steroid receptors and are located on the surface of cells where they elicit rapid biological responses to steroids by mechanisms not involving gene transcription. Several lines of evidence indicate that nongenomic steroid actions mediated by these receptors are particularly susceptible to interference by environmental estrogens. For example, rapid progesterone actions on vertebrate sperm through novel progesterone membrane receptors (mPRs) to induce sperm hyperactivity are inhibited by a wide range of environmental estrogens at relatively low concentrations (0.1μM). Recently, a novel action of estrogens to maintain meiotic arrest through the 7-transmembrane estrogen receptor, GPR30, was identified in fish and mouse oocytes. Bisphenol A was shown to mimic the effects of estradiol-17β at low concentrations (5 nM) to prevent the resumption of meiosis. The effects of bisphenol A exposure on meiosis and fertility of vertebrate oocytes is currently being investigated. Collaboration with Drs. Crews and Gore.

Karen Vasquez, Professor of Pharmacology & Toxicology, The University of Texas at Austin; Division of Pharmacology & Toxicology; Austin, Texas 78712; (T) (512) 495-3040; email:
Research focuses on the areas of genome instability, DNA damage, and mechanisms of DNA repair, with an emphasis on environmental DNA damaging agents. A unique feature of their approach is an emphasis on the role of DNA structure, including non-canonical structures such as triplex DNA, as recognition sites for repair machinery, sources of genomic instability, and as a basis for technology to target DNA damage to specific genomic sites. The lab has demonstrated that naturally occurring non-B DNA structures (e.g. H-DNA and Z-DNA) are mutagenic in human cells and in mice, and can stimulate the formation of DNA double-strand breaks, implicating them in disease etiology. The long-term goals are to determine: 1) the molecular mechanisms involved in the repair of such disease-causing DNA structures; and 2) to determine the extent to which these structure-forming sequences are more susceptible to damage by environmental agents such as UV- and ionizing irradiation as well as PAHs such as benzopyrene. Investigations also include the evaluation of the molecular mechanisms involved in the removal of complex DNA lesions (e.g. DNA interstrand crosslinks) from the human genome and the identification of interactions among the DNA repair pathways in processing these lesions. This area is important because DNA repair mechanisms process DNA damage caused by environmental agents, and genomic instability and deficiencies in DNA repair play major roles in a variety of human genetic diseases. Collaborations with Dr. DiGiovanni and Dr. Wood.

Richard D. Wood, Professor of Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Science Park - Research Division, P.O. Box 389, Smithville, Texas 78957; (T) (512) 237-9431 (FAX) 237-6532; email:
Investigations are targeted to explore the biochemical mechanisms of DNA repair pathways and their associated cellular networks. These pathways comprise the front-line defense against environmental agents that damage DNA. The Wood laboratory has extensive expertise in the biochemistry and cell biology of DNA nucleotide excision repair and has worked out the basic mechanism and reconstituted the process with purified proteins. The Wood laboratory is also working on repair of DNA interstrand crosslinks, which can be caused by chemical compounds found in the environment such as aldehydes. A major object of their research is the action of specialized DNA polymerases that act in DNA repair or damage tolerance. These include REV3L, which protects against UV radiation, POLQ, which protects against ionizing radiation, and the related enzymes POLN and HELQ, which are involved in protection against DNA crosslinkers. Collaboration with Dr. Vasquez.

Casey W. Wright, Assistant Professor of Pharmacology & Toxicology, The University of Texas at Austin; Division of Pharmacology & Toxicology; Austin, Texas 78712; (T) (512) 232-8331 (FAX) (512) 471-5002;
Research is focused on the contribution of inflammatory signaling to the progression of hematological malignancies and solid tumors with an emphasis on the mechanisms of NF-kB regulation by the xenobiotic responsive transcription factor arylhydrocarbon nuclear translocator (ARNT). Many hematologic malignancies such as leukemias and lymphomas have major environmental factors at the core of their etiology, including solvents such as benzene. The Wright laboratory has described a novel regulatory role for ARNT on NF-kB whereby NF-kB activity is modulated depending on the isoform of ARNT present in the cell. For instance, cancer cells predominantly express the long isoform of ARNT, which provides a growth advantage in a number of cancer cell lines, including lymphoma cells. The Wright lab is currently investigating the role of ARNT further by 1) defining the opposing molecular mechanisms between the long and short isoform of ARNT in cancer and 2) analyzing a transgenic mouse, established by the Wright lab, where the long isoform of ARNT is overexpressed in the monocyte/macrophage lineage. This ARNT transgenic mouse will be exposed to a nitrosamine-induced hepatocellular carcinoma model, that is reliant on NF-kB signaling, in order to further characterize the influence of ARNT on the NF-kB pathway. Collaboration with Drs. Mills and Bratton.

Last Reviewed: July 1, 2014

Division Information

Mailing Address:
Pharmacology & Toxicology
College of Pharmacy
The University of Texas
at Austin
107 W. Dean Keeton
Stop C0875
Austin, TX, USA

Email Address: pharmtox

Phone: 512-471-5158

Erickson Authors New Book

"Drugs, the Brain and Behavior" is co-authored by Dr. Carlton Erickson, the college's associate dean for research and graduate studies, and Dr. John Brick, executive director of Intoxikon International.

> Read more about Dr. Erickson's new book.

Gore receives SEBM award

Andrea Gore is named to the SEBM Distinguished Scientist Award.

> Read more about Dr. Gore's new award.

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