Infectious Diseases and Immunology Cluster
The region along the border between the United States and Mexico is a boundary called 'la frontera' where developing and developed worlds meet, resulting in a unique and hybrid environment in nearly every aspect of life. This area is a melting pot combining the unique challenges to human health from each side of the border.
The increased development of the desert regions of West Texas exacerbate this problem, bringing increasing numbers of people into frequent contact with new environments, enhancing the opportunity for the spread of new diseases. Poor sanitation systems, lack of clean drinking water, inadequate health care, poverty, and a high population density contribute to the spread of infectious diseases. The ability of bacteria to become drug resistant by long-term antibiotic treatment can cause previously suppressed diseases to re-emerge. These scenarios are well known in El Paso/Ciudád Juarez, the largest urban community on the U.S.-Mexico border. One of the primary missions of the BBRC is to support and advance research into infectious diseases that concern this community.
Building on UTEP's long-standing strength in parasitology and immunology, the IDI Cluster has become one of the strongest components of the BBRC. The current IDI Cluster includes strong research elements in virology, molecular parasitology, T-cell immunology, drug-design, vaccine development, and epidemiology. In recent years, with support from the RCMI program, UTEP has strategically recruited several outstanding virologists, parasitologists and immunologists to foster infectious disease research. We seek to expand our research program by recruiting new faculty members to provide coverage of key infectious agents like hepatitis A, B, and C viruses and Mycobacterium tuberculosis. We also propose to establish state-of-the art BSL-3 laboratories to facilitate investigation of critical human pathogens and to expand our capabilities to handle potential class A and B bioterrorism agents, particularly NIAID Category A, B, and C priority pathogens.
We wish to maintain a strong infrastructure to support multifaceted research and development of activities, and to promote our capacity for scientific discovery and the translational research required to create the next generation of therapeutics, vaccines, and diagnostics.
Dr. Siddhartha Das, Ph.D . Professor: Dr. Das's laboratory is investigating the role of sphingolipids and lipid rafts in regulating the growth of and differentiation of a parasitic protozoan, Giardia lamblia . Giardia is a major cause of water-borne enteric infection worldwide. The major objective of his laboratory is to use lipid rafts and sphingolipids as novel targets for developing anti-giardial therapy. Dr. Das uses molecular and cell biology techniques to study this parasite. He is also investigating fatty acid metabolism in colon and breast cancer cells.
Dr. Douglas M. Watts, Executive Director, Veterinary Services: Ecology and Epidemiology of Arthropod-borne viruses/diseases. His research is focused on the ecology and epidemiology of West Nile virus and other arboviruses in the El Paso community and on the development and evaluation of a novel recombinant Rift Valley fever viral vaccine for the protection of livestock and humans in Morogoro, Tanzania.
Dr. Renato Aguilera , Ph.D. Professor: 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. Igor Almeida , D.Sc. Professor: Dr. Igor Almeida, Professor: Glycobiology and Omics of Trypanosoma cruzi and development of a vaccine and biomarkers for the chemotherapy of Chagas disease. The research in Dr. Almeida's laboratory is focused on the structural and functional analysis of surface glycoproteins, glycolipids, and lipids of Trypanosoma cruzi , which is the causative agent of Chagas disease, a neglected tropical disease that affects millions of people. His goals are to understand how the parasite interacts with the mammalian host and to identify potential molecular targets for development of a vaccine and biomarkers for the follow-up of the chemotherapy of this deadly infection.
Dr. Delfina C. Dominguez, Ph.D., MT(ASCP), Professor of Clinical Laboratory Sciences: Her research focus is in infectious diseases. Areas of interest include: molecular diagnostics (detection of pathogens and biomarkers), clinical microbiology (antimicrobial resistance) and microbial physiology (investigate the role of calcium (Ca2+) in bacteria and its potential link to infection and pathogenesis). Resistance to antibacterial agents in healthcare settings is an increasing contributor to morbidity, mortality and rising healthcare costs. Many bacteria have become multidrug resistant therefore there is a critical need for the development of fast and accurate detection methods such as point of care (POC) devices and nanoparticles for rapid diagnosis and treatment of disease as well as novel therapeutic approaches to treat antibiotic resistant infections (School of Pharmacy and Chemistry collaboration). Currently Dr. Dominguez’s lab is actively working on the validation of POC biochips for the detection of pertussis, food pathogens and multidrug resistant markers. They are also testing synthetic organic compounds and plant extracts (chemistry collaboration) that may have antimicrobial effects against various bacteria. Ca2+ play a pivotal role as a regulator in many eukaryotic cells. However, the role of Ca2+ in bacteria remains elusive. During infection, metal levels change significantly affecting host-pathogen interactions. Bacterial pathogens must possess mechanisms to adapt and survive in harsh environments such as high calcium levels. The focus of her lab is to study Ca2+ sensing proteins, Ca2+-binders, Ca2+ transporters and corresponding genes. Results from Dr. Dominguez’s laboratory suggest that some proteins that are vital for various metabolic processes may be regulated by calcium ions. Furthermore, some of these proteins appear to be transporters or associated to various transporters, which are up or down-regulated by external calcium ion concentrations. Dr. Dominguez is also very interested in studying antimicrobial efflux pumps and explore the possibility of their regulation by Ca2+ ions.
Dr. Kristine Garza , Ph.D. Associate Professor: The overarching focus of Dr. Garza's research is to understand the interactions between T cells and antigen presenting cells (primarily dendritic cells and macrophages) and how these interactions are affected by agents such as adipokines or anthropogenic airborne particles in the initiation and maintenance of T cell-mediated immunity. Specifically, they are assessing the effects of leptin on dendritic cells and of nanocarbon particulates on macrophages with the intent of determining what role these agents may play in the induction of productive T cell immunity in obese patients (leptin) or in the lungs (nanocarbon particles).
Dr. Kyle L. Johnson, Ph.D. Associate Professor: Dr. Johnson's laboratory studies the mechanism of viral RNA replication, using members of the nodavirus family as a model system. One focus of the laboratory is the development and testing of candidate vaccines against emerging diseases with relevance to the border region, namely tick-borne encephalitis (TBE) and West Nile virus (WNV), both members of the family Flaviviridae . The goals of this project are to develop candidate vaccines for TBE and WNV and to test their immunogenicity in mice. The project incorporates three novel concepts, namely the use of NoV RNA replicons to amplify individual TBEV and WNV mRNAs in the yeast Saccharomyces cerevisiae , the inclusion of an NoV protein that suppresses host cellular defenses like RNA interference, and inoculation of mice with purified total yeast RNA containing amplified NoV-TBEV or NoV-WNV RNAs. If the expressed TBEV or WNV proteins elicit a cell- or antibody-mediated immune responsein the inoculated animals, challenge experiments will be used to determine whether the vaccine candidates can protect against a lethal dose of TBEV or WNV.
Dr. Robert Kirken, Ph.D.Professor: is Principle Investigator of the RCMI grant that supports the BBRC, Full Professor and Dean of the College of Science. His research interests are in cytokine signaling and the regulation of T-cell responses. Specifically, his Molecular Immunoregulation laboratory examines the role of interleukin-2-induced activation of intracellular Jak/Stat signal transduction pathways that may serve as drug targets for immunomodulation. Pharmacological manipulation of these pathways may translate directly into greater successes in organ or tissue transplantation, and improvements in the treatment of autoimmune disorders, both of which are key health concerns for the border region and beyond.
Dr. Manuel Llano , Associate Professor: LEDGF 75, HIV replication. Viruses are obligate parasites and have evolved an essential dependency on cellular factors for replication. Therefore it is expected that cellular proteins that are essential for HIV-1 infection, and dispensable for cellular physiology, could constitute additional therapeutic targets to halt HIV-1 replication. Contrary to HIV-1 proteins, cellular proteins exhibit a significant low rate of mutation and consequently it is expected that drugs against cellular targets will encounter fewer viral drug resistance mechanisms. Dr. Llano's laboratory focuses on this emerging field of antiviral therapy. Specifically, we are involved in the identification of cellular cofactors of HIV-1 replication and their characterization as novel therapeutic targets.
Dr. Rosa Maldonado , D. Sc. Associate Professor: The focus of Dr. Maldonado's research is to develop novel immune- and chemotherapy approaches to treat Chagas' disease and leishmaniasis. Dr. Maldonado uses molecular, cellular and biochemical methodologies to characterize and validate potential drug targets, as well as the development of high-throughput systems for drug screening.
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. Hugues Ouellet , Ph.D. Assistant Professor: The major research focus of Dr. Ouellet is to elucidate the role of cholesterol oxidation activities in M ycobacterium tuberculosis (Mtb), the cause of more than 2 million deaths per year worldwide. His laboratory is particularly interested in deciphering the cholesterol degradation pathway and identifying the oxido-reductases essential for the initial infection, as well as persistent infection. Another interesting aspect is the potential impact of oxysterols on host-Mtb interactions, and more specifically the modulation of the immune response. His long-term goal is to validate cholesterol catabolism as a new therapeutic target for Mtb infection.
Dr. German Rosas-Acosta, Ph.D. Associate Professor: Dr. Rosas-Acosta's laboratory investigates the interplay between the cellular sumoylation system and viral infections. Hislaboratory has found that several proteins encoded by influenza virus are targeted by this post-translational modification system. Therefore, they are currently investigating the functional role played by sumoylation during influenza virus infection, and they are exploring the possibility that augmentation of the overall activity of the sumoylation system may neutralize influenza multiplication in the infected cell. Other research interests pursued in the lab are the global regulation of the cellular sumoylation system by phosphorylation of the modifier (SUMO), and the interplay between nuclear traffic and sumoylation.
Dr. Jianjun Sun , Ph.D. Assistant Professor: Dr. Sun's research interest is to investigate molecular pathogenesis of Mycobacterium tuberculosis and Bacillus anthraces . They are particularly focusing on structure and function of bacterial toxins and virulence factors and their roles in pathogenesis especially the protein pore formation and membrane translocation.
Dr. Charles Spencer, Ph.D. Assistant Professor: Dr. Spencer's research interests are in zoonotic and re/emerging bacterial infectious diseases and the disease burdens of such accumulating at national boundaries. Currently, the laboratory focuses on Francisella tularensis , the causative agent of tularemia and potential bio-weapon, and Mycobacterium tuberculosis , the causative agent of tuberculosis. These bacteria survive in cells of the immune system and are thereby protected from much of the immune response. In order to eliminate infection, small molecules of the immune system called cytokines must be released into the system to activate the cells where these bacteria survive. However, over-production of these same cytokines results in high levels of inflammation which is detrimental to the host. Recent results suggest that a specific lymphocyte population may regulate the production of this cytokines. The goal of Dr. Spencer's laboratory is thus to develop therapeutic interventions for such inflammatory bacterial infections.
Dr. Charlotte Vines , Our laboratory studies immune functions of the G protein-coupled receptor, C-C chemokine receptor 7 (CCR7). CCR7 guides cells to and within lymphoid tissues and has vital functions in immunity and tolerance. CCR7 is involved in organizing thymic structure and function, lymph-node homing of naïve and regulatory T cells via high endothelial venules and immune-induced lymph-node migration of dendritic cells via afferent lymphatics. CCR7 also plays an important role in T-cell/B-cell interactions leading to antibody production. In examining the normal functions of CCR7, we have determined that the two ligands, CCL19 and CCL21, mediate differential internalization of the receptor via arrestin-dependent and arrestin-independent mechanisms, respectively. This is important as several of our studies have described the basis of biased signaling events that are initiated through ligand binding to this endogenous receptor. In this capacity, we have described signaling pathways through both CCL21 and CCL19 ligands. The CCL21 ligand activates a member of the phospholipase C family to control migration of naïve T cells into lymph nodes during an adaptive immune response. In addition, we have shown that CCL19 ligand signals to differentially regulate interactions of naïve T cells with activated dendritic cells, via extracellular regulated kinase 5, and Krüppel-like factor 2. These studies have led to a better understanding of the role of CCR7 and each of its ligands in during the adaptive immune response. Recently, we have published several studies describing our efforts to understand how immunotherapies limit the progression of the experimentally induced autoimmune encephalomyelitis model of multiple sclerosis. As CCR7 and its ligands have been linked to autoimmune disease such as multiple sclerosis, Sjogren’s disease and Crohn’s, our long-term goal is to define pharmacological targets that can be used to aggressively treat autoimmune diseases.
Dr. Jianying Zhang , M.D., Ph.D. is a Professor of Biological Sciences. Research in Dr. Zhang's laboratorymainly focuses on two projects. 1) Humoral autoimmune responses associated with transition from HBV or HCV infection to liver cancer; 2) Functional study of tumor-associated proteins p62/IMP2 and p90/CIP2A in cancer.