Our laboratory aims to provide conceptual advances in host-pathogen interactions across multiple scales, from within-host processes to community-level dynamics. We apply field, experimental, molecular, modeling, and database approaches to diverse study systems, including insect pathogens, avian diseases, bat viruses and mammal parasites. Specific themes we address include: host behavior and infectious disease processes, environmental and genetic determinants of host resistance and pathogen virulence, and anthropogenic processes affecting disease dynamics. We also study insect ecology, evolution and conservation, especially through our work with monarch butterflies. Our lab maintains a supportive environment that values interdisciplinary exchange, creativity, collegiality and engaging in outreach and education.
Our laboratory focus is the characterization of enveloped virus entry. Specifically they are interested in the mechanism of virus-cellular fusion utilizing arenaviruses as their model. They perform structure-functional analyses on the Old World arenavirus glycoprotein complex. As they define the functional micro-domains within the protein, they hope to provide new targets for therapeutics and vaccine development.
Research Interests One of the goals of our laboratory is to understand the role of polyphosphate (polyP) from pathogenic organisms in their interaction with their hosts. PolyP is accumulated in acidocalcisomes, the only organelles known to be present from bacteria to human cells, and is abundant in pathogenic fungi and trypanosomes that infect millions worldwide. The virulence of many human pathogens depends on polyP. Furthermore, polyP can be secreted from platelets and mast cells, providing pro-coagulant and pro-inflammatory activities. We integrate our studies on polyP with the analysis of inositol pyrophosphate (InsPP) metabolism and signaling. These novel cellular messengers have the ability to transfer the b-phosphate of the pyrophosphate moiety to pre-phosphorylated serine defining a new posttranslational protein modification called pyrophosphorylation. Therefore, we can hope to not only illuminate novel basic cell-biological aspects but also to discover novel regulatory mechanisms in thrombosis, inflammation, innate immunity, cancer, and parasitic infection in humans.
Our laboratory uses experiments, field data, and quantitative models to characterize and understand the dynamic and stochastic processes that determine fluctuations, spatial distribution, and extinction of biological populations. Our overarching aim is to produce socially responsible and actionable scientific knowledge in the service of human and environmental welfare.
Areas of interest include the theory of extinction, the problem of coexistence, emergence and spread of infectious diseases, management of invasive species, and critical phenomena in ecology and epidemiology. Applications of our work include epidemic preparedness and forecasting (in both wildlife and human populations), conservation of rare and endangered species, and management of invasive species.
Our laboratory is interested in bacterial metabolism and physiology. Much of the work we do is performed in Salmonella enterica because we can do sophisticated genetic analyses of strains. We are currently focused on three areas of research. First, we study metabolic pathway integration. We identified the cobB gene of Salmonella enterica as a new member of the SIR2 family regulatory proteins in eukaryotes whose activities are needed for gene silencing and cell aging. Our report was an important contribution to this field of research and led to the identification of two enzymatic activities associated with these proteins.
Our laboratory studies the ecology of infectious diseases with a specific focus on linking processes across scales. We investigate how behavioral, ecological, and physiological processes at the individual level shape interactions between hosts and their parasites, and the consequences for population and community-wide patterns of disease. Our work combines field studies with laboratory approaches (e.g. molecular, immunological) and theory to address core questions about the ecology of infectious diseases in wild animal populations.
- Developing new assays that leverage next-generation DNA sequencing
- Determining genetic consequences of human activities and contaminants
- Developing new approaches to understand germline mutations
- Developing and using shared genomic resources for non-traditional biomedical model organisms
Our Laboratory explores mathematical and computational models that connect genes to ecology. His current direction of research includes (i) integration of multiple omic technologies (transcriptomics, metabolomics, lipidomics, proteomics, etc) capturing the dynamics of host-pathogen interactions into mathematical, computational, and statistical models, (ii) landscape epidemiology of malaria, particularly in regards to the design of public health policies that address asymptomaticity and the spread of drug resistant genes and in areas of low endemicity, and (iii) genetic control of invasive species via autocidal organisms, which are produced via phenotypic and genotypic manipulations. Dr. Gutierrez also specializes in data management of very large and heterogeneous biological datasets.
Blood/material interaction is critical to the success of implantable medical devices, ranging from simple catheters, stents and grafts, to complex extracorporeal artificial organs which are used in thousands of patients every day. There are two major limiting factors to clinical application of blood contacting materials: 1) platelet activation leading to thrombosis, and 2) infection. Despite a thorough understanding of the mechanisms of blood–surface interactions, and decades of bioengineering research effort, the ideal non-thrombogenic prosthetic surface remains an unsolved problem. An equally significant problem is that 1 out of every 20 central venous catheters results in at least one infection, and up to 40% of all indwelling catheter devices become infected. The Centers for Disease Control and Prevention estimates that roughly 1.7 million hospital-associated infections, from all types of bacteria combined cause up to 99,000 deaths each year and $28-$45 billion/year associated costs. Dr. Handa’s research is highly translational and interdisciplinary in nature. Their multidisciplinary team is developing biocompatible coatings for medical device applications. They are working towards
Dr. Handa’s research is highly translational and interdisciplinary in nature. Their multidisciplinary team is developing biocompatible coatings for medical device applications. They are working towards fundamental understanding of cell/protein-surface biomolecular interactions, developing and optimizing novel biomaterials and testing these materials in appropriate animal models. Due to the critically important nature of this research field, they have been funded by NIH (via academic and industrial grants). The novel materials they are developing could lead to a significant improvement in existing medical devices by reducing complications due to fouling, thrombosis, and infection and potentially decreasing morbidity, mortality, and costs by shortening hospital stay while increasing survival. Visit the Handa Research Group
Professor, Infectious Diseases
Our Laboratory focuses on the transmission, ecology, evolution, genomics, and transcriptomics of Bordetella species, which include the bacterial pathogens that causes whooping cough in humans and other mammals. They propose to have the PREP@UGA scholar investigate the ecological and evolutionary interactions of Bordetellae with each other (i.e. co-infections of Bordetella species within mice hosts), and between Bordetella species and the resident nasal bacterial community of the mice hosts to examine how the microbiota influences the colonization and invasion ability of Bordetellae.
The student will be involved with in vivo (e.g. live) mouse experiments, as well as general microbiological techniques to grow bacteria (e.g. make culture media), identify the microbiota community using culture techniques, and in vitro (i.e. glass) experiments. S/he will work collaboratively with members of our group to understand the larger picture of Bordetellae ecology. The student may also gain experience with next generation sequencing to identify non-culturable bacterial communities in the mice, and utilize several immunological techniques such as western blots, ELISA (enzyme linked immunosorbent assay), and flow cytometry to examine how the immune system mediates the interaction between co-infected Bordetellae species.
General everyday microbiological lab experiences include growing and enumerating bacterial strains, using aseptic techniques, performing various assays and making culture media.
Our Laboratory focuses on parainfluenza virus 5 (PIV5) as a model to probe how PIV5 evades host innate immune responses and how PIV5 takes advantages of host proteins to replicate efficiently at the molecular level in host cells. We have identified the first viral mRNA that activates interferon expression and we have identified host kinases that are critical for replication of paramyxoviruses. Taking advantage of knowledge generated from our virus-host interaction studies, we have been developing antiviral drugs by targeting host proteins such as kinases that are critical for replication of paramyxoviruses.Mumps virus is a re-emerging human virus that does not have an ideal animal model for studies of its pathogenesis. We have been working on developing suitable animal models (wild type mouse, genetically modified mouse, ferret and non-human primate) for mumps virus. We have developed the first animal model for mumps virus that mimics human diseases.
Our Laboratory focus is to measure, understand, and solve the problems presented by drug-resistance in nematode parasites. Over the past half century, the availability of cheap and effective anthelmintic drugs has led to an almost complete reliance on these chemicals for parasite control in animals. Chemical-based parasite control was extremely effective for many years, but they now know that this strategy has turned out to be shortsighted and unsustainable.
Parasite drug resistance is now recognized globally as one of the greatest health threats to grazing livestock, and has recently been demonstrated in heartworms of dogs. Also, in recent years there has been a dramatic increase in the use of mass drug administration to reduce the morbidity associated with helminth infections of humans, raising the likelihood that anthelmintic resistance will become a public health concern in the near future.
Our Laboratory is interested in parasite genomics and the biology of genome evolution. The genomes of parasitic eukaryotes are often highly-reduced, devoid of recognizable mobile elements and riddled with intracellular and lateral gene transfers. Our approach is to apply molecular, computational and phylogenetic tools to the analysis of parasite genomes. Projects include the development of tools for data integration, data mining, comparative genomics and the systems biology of host-pathogen interactions. Research focuses on Toxoplasma gondii, Cryptosporidium species and Plasmodium species. Researchers in our group work at the bench, at the computer, or both.
Our Laboratory is interested in how immunity is regulated at mucosal surfaces. While our research is focused on the anti-viral CD8 T cell response to respiratory infection, we understand that the development and long-term maintenance of these cells is directly influenced by signals which precede their activation. Therefore, we have begun to elucidate the roles of early innate signals on the development of anti-influenza memory CD8 T cells. Since these T cells provide long-lived heterosubtypic immunity, it is important that we understand the factors which regulate their fate in order to improve current influenza vaccine protocols.
Current research questions include
- How does the route of infection (respiratory vs systemic) affect the memory CD8 T cell program?
- How do NK cells, particularly via direct influenza recognition, regulate their intrinsic function and subsequent CD8 T cell responses?
- How do respiratory-derived cytokines alter CD8 T cell fate and immunity?
Our Laboratory is primarily focused on studying the “life history” of the thymus, the primary lymphoid organ responsible for the generation of T cells. This approach encompasses the evolution, fetal development, postnatal function, and aging of this critical organ. Our basic hypothesis is that these diverse aspects of the biology of the organ are controlled by common regulatory networks, cellular dynamics, and physiological processes. We also study the parathyroid, which is required for calcium homeostasis, and has a shared developmental ontogeny with the thymus. We use a variety of approaches to accomplish these goals, including genetic analysis of tissue-specific and inducible mutant mouse strains, comparative and experimental embryology, and immunological techniques.
Our Laboratory is primarily focused on Human African trypanosomiasis is caused by the protozoan parasite Trypanosoma brucei. Our long term goals are to use small molecules that interfere with important physiological processes in the parasite to (i) understand molecular cell biology and phosphotyrosine signaling pathways, and (ii) identify essential or regulatory proteins with chemoproteomics approaches, and (iii) genetically validate new targets for anti-trypanosome drug discovery. Trypanosome pathways of interest include endocytosis of transferrin, protein translocation into the endoplasmic reticulum, flagellum morphogenesis, cell polarity, and cell cycle regulation.
Our Laboratory focuses on developing an understanding of immunoprotective and immunopathogenic processes in infections during pregnancy, with a particular focus on Plasmodium falciparum malaria and its impact on placental function and fetal outcome. Using a combination of field studies in malaria-endemic western Kenya, laboratory studies of fetal placental cell responses to malaria parasites, and a novel mouse model, we are investigating the interrelated roles of inflammation and coagulation in placental malaria pathogenesis. We are also working to establish the molecular pathways involved in malaria-associated placental cell destruction. We are conducting parallel studies in a mouse model for another severe manifestation of malaria, cerebral malaria, which appears to share common pathogenic pathways with placental malaria. In collaborative work, we are also pursuing studies of candidate antigens for malaria vaccines and novel vaccine platforms.
Our Laboratory focuses on metabolism and drug development against protozoan parasites. We are particularly interested in understanding calcium signaling and storage in Toxoplasma gondii, an intracellular pathogen of humans and animals. It has been shown that calcium plays a critical role in T. gondii virulence but very little is known of the molecular mechanisms involved. Previous work from our laboratory characterized calcium rich acidic compartments in T. gondii and other protozoan parasites (Nature Rev. 3:251, 2005). Presently we are studying the role of extracellular calcium in parasite virulence and how acidic stores regulate calcium entry. We are specially interested in finding the molecular players involved which appear to be different from the mammalian cells ones. Our laboratory uses a variety of genetic tools and reagents available in our community to answer biochemical and physiological questions.
We are presently studying the functions and biogenesis of this organelle. We are also interested in the isoprenoid pathway of Toxoplasma gondii (See scheme on the left). Work in collaboration with other laboratories is centered on testing isoprenoid pathway inhibitors against Toxoplasma growth in vitro and in vivo.
Isoprenoids are an extensive group of natural products with diverse structures consisting of various numbers of five carbon isopentenyl diphosphate (IPP) units. A central enzyme in the pathway, the farnesyl diphosphate synthase (FPPS) catalyzes the formation of farnesyl diphosphate (FPP), a precursor of critical molecules of fundamental biological functions such as dolichols, heme a, cholesterol, farnesylated proteins and others. This enzyme is a validated target for drugs and bisphosphonates, which are specific FPPS inhibitors, inhibit parasite growth in vitro and in vivo. Our hypothesis is that the isoprenoid pathway constitutes a major novel target for the treatment of toxoplasmosis.
Our Laboratory aim is understanding the biology of the deadly human malaria parasite, Plasmodium falciparum. It is a disease that infects nearly 500 million people and causes almost a million deaths each year. Our goal is to leverage our understanding of the parasite biology towards better drugs and strategies for eliminating this ancient scourge of humanity. We deploy a wide variety of tools to study the parasite including cellular biology, chemical biology, molecular biology, and biochemistry. These tools are being utilized to study how the parasite establishes a suitable habitat for growth within human red blood cells. In particular, we want to determine how the parasite targets several hundred proteins to various subcellular locations within the infected red blood cell. We can then disrupt these transport processes thereby rendering parasite incapable of growth within red blood cells and therefore unable to cause disease.
Our Laboratory focuses on the main drivers of vector-borne disease transmission is the ecology of the insect vector. Changes in climate and landuse alter ecological relationships vectors have with their hosts and parasites / pathogens, resulting in shifts in transmission. Our research applies ecological and evolutionary theory to better understand: 1) the host-vector-parasite / pathogen interaction, 2) key environmental drivers of transmission, and 3) how environmental change will affect vector-borne disease transmission.
Our Laboratory is focused on parasites that have been associated with food and water borne outbreaks. Because of current practices in the production and processing of food products, there is a need for studies aimed at the dynamics of disease transmission.
Detection assays that are sensitive and specific for human and animal pathogenic parasites in food products are being evaluated, as well as biological and environmental samples. They focus on the testing, development, and evaluation of methodologies for parasite inactivation in food products, and the study of risk factors associated with parasitic foodborne transmission.
Their goal is the development of safer produce and food products. The parasites currently being studied in this laboratory include Cryptosporidium parvum, Giardia lamblia, Cyclospora cayetanensis Toxoplasma gondii, and Neospora. Since the U.S. imports a large amount of fresh produce and some of this has been implicated in foodborne outbreaks, it was necessary and logical to initiate a training program where scientists from different institutions could become familiar with these parasites. For this two strategies have been initiated: 1) a training program for international scientists and 2) informing the scientific community of the importance of food parasitology as an integral part of food safety. Additionally epidemiological studies on diarrheal illness in children in Peru are being developed, particularly looking at risk factors and environmental conditions that favor the presence and survival of these parasites.
Our Laboratory is jointly with the Odum School of Ecology and the Department of Infectious Diseases at the College of Veterinary Medicine. We are interested in the epidemiological, ecological and evolutionary consequences of host-parasite interactions. Research is largely theoretical (e.g., computer simulation of disease outbreaks) but the questions are often motivated by field and laboratory data, which leads to inter-disciplinary research with veterinarians, virologists, geneticists and ecologists, among others.
Our main focus is on understanding how processes combine to shape patterns of disease at scales from amino acids up to global populations. Influenza has proved a great study system to illuminate these mechanisms. Using equine influenza data we have worked on optimal vaccination strategies, calibration of immune escape and transmission potential. We have also used avian influenza as a model system to consider when zoonoses are more likely to establish via multiple cross-species transmission rather than direct adaptation. However, we are not a disease-specific lab, but rather we look to available data to motivate and address a range of infectious disease issues.
Theoretical work includes applied questions such as determining when basic measures like quarantine actually work and also more fundamental problems including how parasite diversity and host heterogeneity interact to modulate disease risk in populations. Recently we have begun to integrate evolutionary thinking into our approach, because the ability of pathogens to evolve can cause problems such as drug-resistance, antigenic drift and increases in virulence. Part of our work aims to understand the processes driving change in parasite populations.
Our Laboratory focus is to understand the role of parasite adhesion proteins in the interaction of Plasmodium falciparum with receptors on host cells. The particular parasite proteins I am interested in are all members of the duffy binding-like (dbl) superfamily of adhesion proteins. Different members of this large family of related proteins have been demonstrated to play a central role in two critical events in the parasites life cycle: invasion of red blood cells and adherence of parasitized red blood cells to the vascular endothelium and to placental syncytiotrophoblasts. We are currently characterizing one putative erythrocyte binding protein, to determine its role in red cell invasion. Related work seeks to determine the degree of gene polymorphism and differences in gene expression in the erythrocyte binding protein family.
Recently we have also begun to test the expression of various Plasmodium proteins in a novel expression host, the free-living protozoan Tetrahymena thermophila. We have shown that proteins such as TRAP and the CSP can be expressed in Tetrahymena, and appear to be functional. We are now investigating the use of the Tetrahymena expression system for characterization of the erythrocyte binding protein family of Plasmodium falciparum.
Our lab is also part of a collaborative effort with the laboratory of Dr. Julie Moore in this department to study how the binding of parasitized erythrocytes to host cells effects host cell function, particularly as it relates to immune function.
Our Laboratory focus is to identify, isolate and analyze virulence factors from Mycobacterium tuberculosis, M. shottsii, and other pathogenic mycobacteria of humans and animals. The primary focus is currently on examining a number of mycobacterial genes for the purpose of understanding their regulation and control of the host-pathogen interaction. Ultimately, these genes, gene products or associated factors could be used as targets for (the causative agent of tuberculosis) and their genetic coding regions for potential use as vaccine and diagnostic candidates and perhaps as guides for novel disease treatments. An example of one of our studies involves a gene product only expressed during the latent stage of tuberculosis (the most common and most difficult phase to treat). The currently available diagnostic test for tuberculosis, the tuberculin skin test, is not always accurate, does not reflect active disease or latent disease, and most unfortunately, once a person is vaccinated with the currently available BCG vaccine, the skin reaction is positive for at least seven years. Additionally, since the BCG vaccine is not effective in a large fraction of the population, and as previously mentioned causes a positive tuberculin skin reaction, this vaccine is not recommended for use in the United States. We are currently attempting to define the role of this protein in disease and are engaged in an international field trial using this protein as a diagnostic for latent infection.
Our Laboratory investigates reactive oxygen species-based host-microbe interactions at the respiratory mucosal surface. Reactive oxygen biology in the airways is of extraordinary importance because of permanent direct exposure to atmospheric oxygen. Our primary focus is to study the pathogenic mechanism of the opportunistic bacterial pathogen, Pseudomonas aeruginosa and the airway immune response mediated by airway epithelial cells and white blood cells called neutrophil granulocytes. Reactive oxygen species are involved in immune mechanisms used by both, Pseudomonas and host cells. The laboratory mainly uses primary human cells and clinical samples obtained from patients. Our findings will help to understand the pathogenesis of cystic fibrosis, COPD and bacterial pneumonia.
Our Laboratory focuses on designing, developing and testing vaccines for viral diseases such as influenza, dengue, respiratory syncytial virus, chikungunya virus, Ebola and HIV/AIDS. The work he began while a faculty member at the University of Pittsburgh to create a universal vaccine to protect against all strains of seasonal and pandemic influenza has resulted in a new vaccine platform. In 2012, an agreement was signed between Sanofi Pasteur and the University of Pittsburgh for continued development and commercialization of influenza vaccines based upon this platform.
“I am excited to join the research faculty at the University of Georgia to develop cutting-edge, life-saving vaccines,” Ross said. “We expect to build a critical mass of scientists centered on immunology and vaccines for infectious diseases. Working together with biomedical and infectious disease researchers at UGA and the other leading institutions in the state of Georgia, we will work towards a world-class research community focused on developing the next generation of novel vaccines and immunotherapeutics.”
Understanding the impacts of diseases on wildlife populations and the potential for these species to act as reservoirs or sentinels for livestock, poultry, and human diseases represent the central missions of our lab. Most of my current work is oriented towards the epidemiology of viral and vector-borne diseases, specifically: bluetongue and the epizootic hemorrhagic disease viruses in white-tailed deer; avian influenza viruses in free-living duck and shorebird populations; vesicular stomatitis virus vector and contact transmission; West Nile virus in peridomestic avian species;
and Ehrlichia chaffeensis in white-tailed deer.
Specific research objectives are variable reflecting the multi disciplinary mix of our immediate group and an abundance of intra- and extramural collaborative opportunities, and range from improving basic and molecular diagnostic tests, understanding pathogenesis, development of sentinel systems involving wildlife, understanding mechanisms involved in pathogen transmission and persistence, to molecular epidemiology.
Upon invasion of a host cell, intracellular pathogens must actively ensure their survival in an immediately hostile environment. One such survival tactic of some pathogenic bacteria is through the subversion of host membrane fusion machinery, thereby inhibiting phagolysosomal fusion and subsequent delivery of the bacterium to the host degradative lysosome. The foodborne pathogen, Salmonella enterica, and the causative agent of Legionnaire’s disease, Legionella pneumophila, are examples of such bacterial pathogens that utilize this particular survival tactic. While evading host cell defenses in this manner is key to the organism’s ability to cause infection and disease, the mechanisms underlying these evasion pathways remain poorly understood. Many studies have tentatively identified bacterial factors thought to be important for the disruption of normal host membrane dynamics, but the biochemical analysis of these factors remains lacking. By employing a powerful in vivo and in vitro model system of eukaryotic membrane fusion, my laboratory will investigate the biochemistry of eukaryotic membrane fusion, identify and biochemically characterize bacterial effectors capable of modulating membrane fusion, and finally analyze these activities within the context of pathogenesis.
Vacuoles of the budding yeast Saccharomyces cerevisiae serve the equivalent physiological function of the mammalian lysosome, and undergo constant rounds of fission and homotypic (self) fusion in response to cellular growth conditions. Isolation of these fusogenic organelles from yeast is now a straightforward task, and robust colorimetric assays have been developed to assay the multi-stage process of their fusion in vitro. As an excellent model of general eukaryotic SNARE-, Rab GTPase-, and SM protein-dependent intracellular membrane fusion, the yeast homotypic vacuole fusion system will comprise the backbone of our genetic, molecular, and biochemical approaches. Initial studies in the lab will characterize factors that allow an organism to drive a given membrane fusion event with a specific set of fusion machinery. The recent discovery that a yeast protein complex (the so-called HOPS complex) provides a proofreading activity to ensure proper homotypic vacuole fusion will be further studied. In addition, we will conduct genetic and biochemical screens of the intracellular pathogens Salmonella and Legionella to identify bacterially-produced inhibitors of vacuole fusion in vivo and in vitro. Mechanistic information gleaned from these studies will open new avenues towards the detailed study of basic bacterial pathogenesis.
Our Laboratory focuses on understanding how the host’s immune system protects insects from parasitoid invasion and reciprocally, how parasitoids overcome host defenses. This includes the study of microbial symbionts like polydnaviruses that are carried by many parasitoids and that play a key role in suppressing the immune system of host insects.
In close collaboration with our UGA colleague Dr. Mark Brown, we also study vector arthropods like mosquitoes that transmit human diseases. Here our interest is primarily in how the mosquito immune system responds to invasion by different pathogens including the parasite that causes malaria in humans.
Another study area focuses on life history evolution and how parasitic lifestyles have affected developmental processes. We are particularly interested in polyembryonic parasitoids that exhibit many dramatic developmental adaptations including a sophisticated caste system that resembles in many ways the social systems of bees, ants and termites.
Most of our projects involve parasitic wasps (parasitoids) that develop as immatures in or on the bodies of other insects but that are free-living as adults. Parasitoid wasps are among the most species-rich group of organisms on earth.
Our Laboratory focuses on the immunology and pathogenesis of Trypanosoma cruzi infection and the resulting disease syndrome known as Chagas disease. T. cruzi is a protozoan parasite that infects approximately 18 million people in Latin America with 90 million more at risk of infection. Chagas disease is the single most common cause of congestive heart failure and sudden death in the world and the leading cause of death among young-to-middle-age adults in endemic areas of South America . There are no vaccines for prevention of T. cruzi infection and current chemotherapeutic regimens are of limited efficacy. Three broad questions are being addressed by the research in the Tarleton lab: 1) How is immune control initiated and maintained during the infection, 2) How does T. cruzi manage to avoid immune clearance and maintain an infection for decades in hosts, and 3) What is the relationship between immunity, parasite persistence, and disease development? The ultimate goals of these investigations are to provide insights into the immunologic basis of parasite control and pathogenesis in T. cruzi infection and to use this information to design methods for prevention of infection or intervention in chronic disease.
Our Laboratory interests focus on understanding transmission and pathogenicity of zoonotic influenza virus infection and development of novel approaches to vaccination and the prevention and treatment of viral infections. This utilizes a variety of animal models and disease hosts including mice, ferrets, guinea pigs, and swine. Virology studies include understanding transmission and pathogenic potential of emerging influenza viruses, surveillance, and mutagenesis (reverse genetics) of influenza viruses. Immunology studies involve regulation of innate immune responses to viral infection in humans and animal models, and the immunologic basis for universal influenza vaccination. Disease intervention research includes novel diagnostics, recombinant vaccine and vaccine delivery development, therapeutic applications of RNA interference, and understanding the role of microRNAs in disease. Finally, aspects of the above research are ongoing for other emerging and re-emerging infectious diseases.
Our Laboratory is devoted to understanding the mechanisms that regulate host defense on one hand and tolerance on the other. Signal transducers and activators of transcription (Stats) are a family latent cytosolic transcription factors activated by cytokins and growth factors that regulate this pivotal balance. Activated Stats impart distinct effect or functions on developing naive CD4+ T cells to tune adaptive immune responses. The activation of Stat4 by interleukin 12 (IL-12) and related cytokines is critically important in the defense against intracellular pathogens through the Stat4-dependent induction of the potent inflammatory cytokine, interferon-y (IFN-y). This pathway is particularly relevant in light of the recent escalation in the incidence of multi-drug resistant forms of tuberculosis, a leading cause of infectious death. In order to better understand the physiologic functions of Stat4 as they pertain to cell-mediated immunity, we have performed microarray analysis to identify genes regulated by IL-12. Among many IL-12 inductible genes, we identified the mitogene- activated protein kinase Tpl2 (aka MAP3K8)as a bonafide Stat4 target gene. Current research is aimed at understanding the contribution(s) of Tpl2and other Stat4 target genes to the regulation of T helper cell development and host immune responses to infectious and autoimmune disease settings.
Our Laboratory interest is the drugs (anthelmintics) used to treat and prevent infections with parasitic roundworms (nematodes) in humans and animals. We are also very interested in the mechanisms by which the parasites become resistant to these drugs. Most anthelmintics target the nematode nervous system, causing paralysis and death, so we study the components of the nervous system affected by anthelmintics, specifically nicotinic acetylcholine receptors and glutamate-gated chloride channels.
Our current projects include attempting to unravel the mechanisms of action of ivermectin and diethylcarbamizine against filarial parasites such as Brugia malayi, which is a causative agent of lymphatic filariasis, and Dirofilaria immitis, the dog heartworm. We are applying transcriptomic techniques to try and unravel the effects of drug treatment on the worms and, possibly, the host. Many parasitic nematodes are able to profoundly modulate the host immune system and we are actively testing the hypothesis that the efficacy of the anthelmintics is due, at least in part, to inhibition of this modulation.
Anthelmintic resistance is a major problem in veterinary medicine. It is rampart in livestock parasites, such as Haemonchus contortus, which have become to just about all the drugs available, and has recently been confirmed in heartworm, where only a single class of compound is available to prevent disease. We are seeking to develop and evaluate molecular markers and tests for resistance.
Parasitic nematodes are difficult to study, so we are examining the possibility that genes from parasites can be expressed in the free-living worm, Caenorhabditis elegans, using subunits of the nicotinic acetylcholine receptor as a model.
Our Laboratory studies a wide range of pathogens of importance to wildlife, domestic animal, and human heath. We stress the need for interdisciplinary approaches to study these pathogens and fully embrace the “One Health” approach as many of these pathogens are important to people and animals.
Below is a partial list of our current studies:
Studies on Baylisascaris procyonis, the raccoon roundworm. Current focus on the seroprevalence and risk factors for exposure in wildlife rehabilitators, the ecology of the parasite in the Southeastern US in raccoons and possible intermediate hosts, the antibody kinetics of a recently developed serologic assay, and the role of domestic dogs and hosts for this parasite.
Health surveillance in numerous species of seabirds in Alaska.
Identification and characterization of mites associated with a mange epizootic in black bears in Pennsylvania with hopes of developing management strategies
Studies on the safety and immunogenicity of vaccines in wildlife species. Numerous types of vaccines are used in wildlife, some of which may not be safe. We are investigating numerous types of vaccines in native carnivores.
Ecology of haemoparasites in birds. Current studies involve several species of ducks, ibis and other waterbirds in the United States and passerine birds in Costa Rica.
Health screening of an isolated population of African lions in Botswana
Ecology of blood parasites in turtles and tortoises. Currently, we are attempting to determine the role of behavior on infection status of aquatic turtles as well as vectors associated with tortoise blood parasites.
Morphology and phylogenetics of coccidia of wildlife. While we focus on coccidia of birds, we also investigate some coccidia (mainly tissue-dwelling species) in mammals.
A ‘save the tick’ campaign. For several years we have been investigating the health of gopher tortoises, a rare and/or endangered species (depending on state). This tortoise is a host for a very host-specific tick, Amblyomma tuberculatum. Through a citizen-science approach, we are trying to understand the distribution of this tick among gopher tortoise populations and factors associated with this disjunct distribution.