Toxicology & Cancer Biology Research Cluster
Human health impacts stemming from exposure to environmental toxicants remains a significant concern in El Paso County. UTEP, one of the country's premier minority-serving institutions, is building a robust research program in Toxicology made possible, in-part, through funds from the BBRC. The Toxicology & Cancer Biology Research Cluster (TCC) promotes and nurtures U.S.-Mexico partnerships aimed at investigating environmental health issues that impact cancer incidence in populations on both sides of the border. To more completely address the issues impacting border health, the TC Project maintains active collaborations with Texas Tech Medical School, La Universidad Autónoma de Ciudad Juárez, the International Boundary and Water Commission and William Beaumont Army Medical Center among other local and regional agencies. It is envisioned that these collaborative efforts will lead to better management of our limited natural resources, increase our level of understanding regarding impacts of contaminants (cellular to ecosystem level) on our environment and ultimately lead to better conditions for human and environmental health along the U.S.-Mexico border.
The Toxicology & Cancer Biology Research Cluster (TCC) of the BBRC promotes and fosters collaboration between PIs within the Project, with other Departments at UTEP as well as with investigators located outside of UTEP (See Fig. 1). The Toxicology & Cancer Biology Research Cluster actively supports aspects of basic research into environmental, human and animal health issues as they relate to the disciplines of Toxicology and Cancer Biology. Many of issues along the U.S.-Mexico border relate to, but are by no means limited to: heavy metal contamination and exposure, water pollution from both domestic and international sources, air pollution and the associated acute and chronic exposure to environmental contaminants originating from the deposition of small molecules that, collectively, pollute the air. To meet the demands of active Toxicology research in the border region, the TC Cluster, to the best of its ability, provides specialized equipment as well as access to research facilities and technical staff. The Toxicology & Cancer Biology Research Cluster also promotes and supports the presentation of research results to international, national and local audiences. Depending on availability of funds, TCC provides support for TC investigators to attend professional meetings and participate in other professional development activities. This overall mission enhances current TC research efforts and increases the future competitiveness of our investigators toward securing extramural funding for student and community education in addition to hypothesis- and need-driven research into environmental pollution issues and their relationship to the incidence of cancer along the U.S.-Mexico border.
Toxicology. The National Institute of Environmental Health Sciences (NIEHS) supports a philosophy that it is better to prevent disease than to treat it. The BBRC’s Toxicology& Cancer Cluster reflects this mission. Our goal is to address how environmental exposures affect health, how individuals differ in their susceptibility to exposures, and how susceptibilities change over time. Further, we will use our proximity to the border to investigate health disparities among complex mixtures, persistent organic pollutants, metals, children's environmental health, and the development of new technologies and models for evaluating chemical effects. Lastly we will focus on water quality issues in the Rio Grande as well as ground and surface waters. The border area is growing rapidly and consequently more pressure will be exerted on existing water resources. These resources are already being rapidly consumed and/or degraded through industrial and municipal uses in the region. Current predictions indicate that booming populations will double the number of people living on the U.S.-Mexico border between 2000 and 2020. This influx of people will increase the magnitude of existing environmental problems, including inefficient wastewater treatment, bi-national air and water pollution, and diseases associated with inadequate human health services and pollution. These impacts will be felt most strongly in the cities. In 1990, less than 33% of the inhabitants of the U.S.-Mexico border lived in cities compared to more than 90% in 1997. Much of this growth is due to the Border Industrialization Program in 1965 and strengthened by NAFTA in 1994. These legislative agreements spawned a large number of industrial plants in Mexico (maquiladoras) that make products for importation by the U.S. Many of these industrial plants lack the environmental controls of U.S. plants. Maquiladoras have poor working conditions, high rates of industrial accidents and toxic exposures to workers. Furthermore, they release large quantities of water pollutants. Thus, the release of diethylhexyl-phthalate, arsenic, lead, chromium, copper, mercury and other hazardous wastes into the water reduces water quality in the region. Water pollution is further increased by agricultural runoff following surface irrigation in the area. The importance of border pollution has been recently acknowledged by both the CDC and EPA in their recent border-directed research initiatives ( http://www.cdc.gov/nceh/hsb/borderhealth/border2012.htm ; http://www.epa.gov/ehwg/mission.html ). Thus, a major focus of the Toxicology/Cancer Biology Project is addressing these environmental issues: inefficient wastewater treatment, air and water pollution, and the impacts of these pollutants on human health.
Cancer Biology. Hispanics are the fastest growing demographic in the United States. In addition, Hispanics make up a large majority (~80%) of the population within El Paso County. Thus, Toxicology & Cancer Biology Research Cluster members are uniquely positioned to investigate health disparities within the Hispanic population. In 2009, cancer surpassed heart disease as the leading cause of death in Hispanics highlighting the importance of increased efforts to solve the many cancer health disparities that exist. The effort of the Cancer Collaborative Group can be divided into three main categories; studies on hematological cancers, on tumor-associated antigens with emphasis on hepatocellular cancer, and on endocrine-related breast and prostate cancers, which are particularly prevalent in the El Paso region. Although prostate cancer incidence in Hispanics is similar to that of non-Hispanic Whites, the incidence of prostate cancer within El Paso County is one of the highest in the state. Thus, the incidence of prostate cancer in El Paso represents a regional health disparity that disproportionately affects Hispanics. In addition, HER-2 expressing breast cancer is 2.8 times higher in Hispanic women than in Non-Hispanic White women. Finally, the incidence of hepatocellular cancers is 2-3 times higher in Hispanics as compared to non-Hispanic Whites.
One of the greatest cancer health disparities that exist within the Hispanic population is related to hematologic cancers. Extensive data analysis by the Leukemia and Lymphoma Society indicates that Hispanic children of all races have the highest rate of leukemia and Hispanic women have the second highest rate of lymphoma. Compounding these health disparities issues is the fact that Hispanics also have a higher risk of treatment failure and therefore mortality from leukemia and lymphoma as compared to non-Hispanic whites. The reason for these health disparities is not known and therefore is a daunting research task to solve. It is also one that we happily undertake.
Human health impacts stemming from exposure to environmental toxicants remains a significant concern in El Paso County. UTEP, one of the country's premier minority-serving institutions, is building a robust research program in Toxicology made possible, in-part, through funds from the BBRC. The Toxicology and Cancer Cluster (TCC) promotes and nurtures U.S.-Mexico partnerships aimed at investigating environmental health issues that impact cancer incidence in populations on both sides of the border. To more completely address the issues impacting border health, the TC Project maintains active collaborations with Texas Tech Medical School, La Universidad Autónoma de Ciudad Juárez, the International Boundary and Water Commission and William Beaumont Army Medical Center among other local and regional agencies. It is envisioned that these collaborative efforts will lead to better management of our limited natural resources, increase our level of understanding regarding impacts of contaminants (cellular to ecosystem level) on our environment and ultimately lead to better conditions for human and environmental health along the U.S.-Mexico border.
The Specific Aims of the Toxicology & Cancer Biology Cluster are as follows:
1. Enhance interdisciplinary research capacities through the acquisition of key instrumentation and the use of BBRC and RTRN core facilities.
2. Hire faculty members with expertise in cancer biology, environmental epidemiology or toxicogenomics.
3. To enhance community engagement through partnerships with regional agencies and institutions.
To achieve these objectives over the next 5 year period, we will:
1) fill two additional pharmacologist- toxicologist positions,
2) provide technical support personnel for the Aquatic Toxicology Wet Laboratory,
3) apply for an NIEHS training grant when the RFA is released, and
4) travel to scientific meetings and workshops to present research findings, identify emerging areas of concern, initiate new collaborations and recruit students and post-doctoral researchers to the Toxicology program at the Unversity of Texas at El Paso.
•To contribute to the health and education of people in the El Paso / Cuidad Juarez community
•To increase the number of trained toxicologists in the border region while addressing toxicological issues of national and regional concern, including increasing our understanding of chemical hazards, exposure, dose, toxicokinetics, and mechanisms.
Dr. Elizabeth J Walsh is Professor in the Department of Biological Sciences and the Director of the Toxicology & Cancer Biology Cluster. The main focus of her work is water quality and impacts of toxicants on aquatic ecosystems. She is particularly interested in a) affects of heavy metals on freshwater invertebrates, b) mechanisms of metal detoxification, and c) impacts of pharmaceutical residuals on aquatic populations. The goal of this research is to better understand how anthropogenic releases into the environment impact natural ecosystems with a regional focus on the Rio Grande and other Chihuahuan desert waters (US & Mexico). Understanding how these pollutants impact water quality will help decision makers make better choices for our water resources that are critical for human and ecosystem health.
Dr. Marc B. Cox is an Associate Professor of Biological Sciences. His research focuses on the molecular mechanisms of toxicity mediated through receptors such as the aryl hydrocarbon receptor (AhR), the orphan nuclear receptors PXR and CAR, and steroid hormone receptors (endocrine disruption). Dr. Cox is also interested in environmental pollution monitoring, and he hopes to use his various receptor functional assays in the lab to test environmental samples (e.g. soil and water) for the presence of contaminants, including polyaromatic hydrocarbons and endocrine disrupting chemicals. In addition, Dr. Cox is interested in developing these assays, some of which are sensitive enough to detect low picomolar amounts of ligand, into tests that can be used in the field to monitor contaminant levels. Simple field test like these would make routine testing more feasible and help prevent environmental exposures that can lead to a wide range of adverse health effects in both wildlife and humans.
Dr. Renato Aguilera , Ph.D. Professor and Director of the BBRC: Dr. Aguilera has established a High throughput (HTS) drug screening facility to determine the activity of novel compounds on cancer cell lines and a variety of microbial agents. With the use of HTS equipment, his group has recently developed assays for screening of chemical libraries on a variety of human cancer cells. The ultimate goal of these assays is to discover compounds that can kill specific cancer cells but not others. In recent months, the simultaneous screening of compounds of various human cancer cell lines has resulted in the detection of novel lead compounds with potent anti-lymphoma and anti-breast cancer activities. This research involves the participation and training of several undergraduates and graduate students; the majority of whom are from underrepresented minority groups.
Dr. Fatima Alshbool is Assistant Professor of Pharmacy Practice. Dr. Alshbool's primary research interest is in the area of cardiovascular disease, and specifically the pathogenesis of thrombotic diseases. Using mouse models and human platelets, and a host of pharmacological and biochemical approaches, she is currently interested in identifying new proteins that regulate platelet function, and understanding their contribution to the genesis of thrombosis diseases. Ultimately, her work should define new means by which platelets proteins can be targeted for therapeutic purposes.
Dr. Siddhartha Das is a professor of Biology at the University of Texas at El Paso (UTEP). His laboratory investigates the lipid metabolism and lipid signaling in parasitic protozoan, Giardia lamblia. Giardiasis caused by Giardia lamblia, is transmitted via infective cysts through contaminated water and prevalent worldwide. He is also interested in identifying the role of arachidonic acid (present in high fat diet) in inducing inflammatory reactions in breast cancer. Dr. Das is on the editorial board and a permanent reviewer for various prestigious journals devoted to biochemistry, microbiology, molecular biology and parasitology. The work in Dr. Das’ laboratory is supported by the grants from the National Institutes of Health (NIH). Over the years, he has mentored many students, post-doctoral fellows, and new faculty members. Currently, he is the director of Immunology and Infectious Disease Cluster of the Border Biomedical Research Center (BBRC) at UTEP, which is supported by a grant from the NIH.
Dr. Giulio Francia , Assistant Professor of Biological Sciences, obtained his Ph.D. from the laboratory of Professor Ian R. Hart at Imperial Cancer Research Fund, UK, on the identification of genes involved in the development of metastatic melanoma. He then undertook postdoctoral training in the laboratory of Professor Robert S. Kerbel at the University of Toronto, where he began to develop models of spontaneously metastatic breast cancer in mice, and in particular ERBB2-positive metastatic breast cancer, which were used to test the effect of ERBB2-specific antibody (trastuzumab)-based therapies on spontaneously metastatic disease. He is interested in the biology of metastasis, and on the development of preclinical models of metastasis to study the effect of different therapeutic approaches on the growth of metastatic tumours.
Dr. Fadi Khasawneh, Associate Professor and Chair Pharmaceutical Sciences. The Khasawneh laboratory research is focused on the study of thrombosis and platelet biology. The primary goal is to delineate signaling pathways involved in platelet activation and to investigate their role in the pathogenesis of thrombotic diseases. They employ a host of molecular, biochemical and pharmacological approaches, as well as thrombosis models in their studies. Their ultimate goal is to identify novel therapeutic agents and/or targets for the management of thromboembolic disorders, such as heart attacks and stroke.
Dr. Robert Kirken , is Professor and Dean of College of Science, and is Principle Investigator of the UTEP BBRC. The goal of the laboratory is to understand the intracellular signaling pathways responsible for mediating T cell activation so that rational strategies to regulate immune responses can be achieved. The intracellular molecules activated by JAK3 are not readily known nor the genes it regulates. Through critical analysis of these signaling pathways it will be possible to utilize pharmaceuticals to manipulate these secondary messengers and subsequently modulate an immune response. Ultimately, these studies will enable Dr. Kirken's lab to develop novel immunomodulatory drugs with therapeutic potential against important clinical conditions such as graft-versus-host disease, allergy, and autoimmune disorders. Rates of allergies and autoimmune disorders (especially lupus and diabetes) are high in the El Paso/Cd. Juarez area.
Dr. Charlotte M. Vines is an Assistant Professor in the Department of Biological Sciences and a member of the Toxicology & Cancer Biology Cluster. The primary focus of her work is understanding how the C-C chemokine receptor 7 regulates migration of tumor cells. She is specifically interested in a) determining how C-C chemokine receptor 7 promotes entry of pediatric T-cell acute lymphocytic leukemias into the central nervous systems of children suffering from leukemia where the disease can find refuge from systemic chemotherapies, b) developing methods to block C-C chemokine receptor 7 induced movement into the central nervous system and c) defining the cellular and immune-mediated mechanisms that promote disease free survival in breast cancer patients who express C-C chemokine receptor 7 in the breast tumor cells. Understanding the signaling events regulated by C-C chemokine receptor 7 will allow us to make more effective drugs that can be used to regulate its function during the progression of different cancers.
Dr. Wen-Yee Lee is an Assistant Professor of Chemistry. The research projects in her group are a) fate and transport of persistent organic pollutants (POPs) in soil, air, and water, b) the occurrence and concentration of POPs in breast milk, and c) occurrence and concentration of endocrine disrupting chemicals in wastewater. Wastewater treatment continues to be a health concern in the region, as facilities in Cd. Juarez are primary treatment operations with limited budgets for supporting operations. Sewage effluents from Cd. Juarez and El Paso have major impacts on local and regional water quality. Dr. Lee's research is the first in our region to investigate the prevalence of endocrine disrupting chemicals in our local water sources.
Dr. Luis R. Martinez, Ph.D., MBA, Associate Professor: The encapsulated fungus, Cryptococcus neoformans, is the most common cause of fungal meningitis, with the highest rate of disease in AIDS patients. This fungus is responsible for 1 million new cases of cryptococcosis and half a million deaths annually worldwide. Preliminary data in Dr. Martinez’ laboratory demonstrates that the capsular polysaccharide released by C. neoformans during infection disrupts the blood brain barrier integrity via the modulation of the expression of tight junction proteins facilitating central nervous system (CNS) invasion. Dr. Martinez’ long-term goal is to dissect the mechanisms regulating C. neoformans CNS invasion and neurotropism, particularly within the setting of immunosuppression. These discoveries will facilitate the development of therapeutics to prevent lethal cryptococcosis.
Dr. Mahesh Narayan is an Associate Professor of Chemistry. His research group is interested in investigating mechanisms of chaperone-catalyzed protein folding reactions in order to develop small molecule mimics that can serve as chemotherapeutics. Apart from his own interests in the identification of potential chemotherapeutic agents, Dr. Narayan also contributes to the structure-based design of potential therapeutic compounds.
Dr. Christina Sobin , Associate Professor, Department of Public Health Sciences, conducts translational interdisciplinary research examining brain and behavior during development. Her laboratory studies cognitive concomitants and sequelae of genetic variants and medical conditions; these provide a natural manipulation of brain mechanisms that may be unrecognized as critical for brain health. Results from their child studies have guided the development of new animal models. Currently, her laboratory studies effects on brain and behavior of early chronic low-level heavy metal exposure, with a focus on lead and arsenic. Her child studies provided new evidence that the hPEPT2*2 genetic variant increases blood lead burden and predicts a specific pattern of neurocognitive deficits in exposed children. In a translational mouse model her laboratory duplicated low exposure levels of their child participants, quantified loss of microglia in dentate gyrus, and are attempting to characterize behavioral effects. Via interdisciplinary collaboration, they are studying additional genetic factors and peripheral organs altered by low-level heavy metal exposure that may impact brain health and resilience.
Dr. Suman Sirimulla, Assistant Professor of Pharmaceutical Sciences, has research interests range from understanding non covalent interactions between protein-ligand complexes, drug discovery, genomics, and personalized medicine to high performance computing and deep learning. Dr. Sirimulla and his collaborators are currently working on several drug discovery projects. These collaborators include experimental scientists across the country. The goal is developing inhibitors for the treatment of multiple diseases. Dr. Sirimulla brings chemical entities to biology using computational tools like docking, pharmacophore modeling, molecular dynamics, ADME predictions, homology modeling, and QSAR studies. He is also working on developing specialized software tools for modeling cellular information processing and decision making.
Dr. Jorge Gardea-Torresdey is Professor and Chair of the Department of Chemistry. The research in his laboratory focuses on: a) phytormediation of toxic metals and metalloids, b) the use of phytohormones and chelating agents to improve the phytoremediation potential of plants, and c) uncovering the mechanisms of heavy metal adsorption by biomass for the improvement of metal phytoremediation. His group also works on developing the use of nanoparticles to solve environmental health problems. Results from his work could provide ways in which to bioremediate local arsenic and lead contamination.
Dr. Hector A. Olvera, Ph.D., P.E. Associate Professor: Dr. Olvera’s research focuses on understanding how the totality of factors within the environment impact health. This includes conceptualizing social and environmental factors that increase risk and also protective factors, and focusing on both disease and healthy states. Specifically, Dr. Olvera’s current work examines the biologic and behavioral mechanisms through which environmental (e.g., air pollution exposure) and social factors (e.g., psychosocial stress) may jointly contribute to disease and health disparities, while explicitly considering the role of positive factors in promoting health and well-being. The goal of the Biobehavioral Research Laboratory (BbRL) is to accelerate the translation of research into effective intervention programs to promote healthy aging and well-being across the life-span.
Jianying Zhang, M.D., Ph.D. , is a Professor of Biological Sciences. Research in Dr. Zhang’s laboratory mainly focuses on two projects. 1) Identification and characterization of tumor-associated antigens (TAAs) as diagnostic markers in human cancer, particularly in liver cancer. His overall goal of the lab is to determine whether a mini-array of multiple TAAs would enhance antibody detection that would be useful non-invasive approach for the early detection of human liver cancer. The expected results from Dr. Zhang’s project will contribute to the reduction of disparities associated with the mortality of liver cancer, which disproportionately affects Hispanic communities, particularly in the El Paso region. 2) Functional study of tum or-associated proteins p62 and p90 in cancer. In this study, functional characterization of two oncoproteins p62 and p90 in breast and lung cancer cell lines have been performed using either gene knock-down or gene overexpression approaches. Preliminary results demonstrated that both oncoproteins p62 and p90 may play important roles in cell proliferation and cancer development.
Dr. Ricardo Bernal is an Assistant Professor of Chemistry. His research interests are primarily focused on the mechanisms that lead to the efficient and precise assembly of large macromolecular complexes from heterogeneous subunits. By combining cryo-Electron Microscopy (cryo-EM) and X-ray crystallography, many of the limitations of each individual technique can be overcome. By fitting in high-resolution X-ray structures of individual components into a relatively low-resolution cryo-EM reconstruction, we can overcome the resolution limitations of electron microscopy. Detailed knowledge of atomic interactions may also provide insight so that it may be possible to design inhibitors that block the interaction of the toxic chemical to its target.
Dr. Guillemina “Mina” Solis is an Assistant Professor in the School of Nursing. She received her PhD in Interdisciplinary Health Science from the University of Texas at El Paso and her M.S.N. from the University of Arizona. Her research currently focuses on Latino immigrant end-of-life care for cancer patients and improving survivorship among breast cancer survivors. Her previous research includes metabolic and psychological disorders, such as diabetes type 2 and its relation with depression and fall injuries among older adults that influence the functional and psychological state of persons affected. Dr. Solis has expertise in clinical nursing science, geriatrics and gerontology, leadership experience in nursing management, and research preparation. She is currently collaborating with other institutions on end-of-life decision making for Latinos & non-Latinos.
Dr. Juan Noveron is an Assistant Professor of Chemistry. His research focus is on the synthesis and characterization of functional bio-inorganic materials with precise molecular composition. In particular, we employ molecular self-assembly processes to develop supramolecular materials with DNA delivery properties. The efficient delivery of genetic material into the nuclei of appropriate cells is one of the greatest challenges in gene therapy. This implies the encapsulation and cell-selective delivery of large segments of DNA. Materials with these abilities will have applications in toxicology especially in terms of drug delivery.