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Infectious Disease Faculty at Virginia Tech

There are overlaps in categories, such as Vector Borne Disease and Environmental Contexts, and most research informs the Public Health Response. The following classifications help locate researchers by their major focus.

• Bacteria Environmental Sensing (Quorum Sensing)
• Food Safety
• Social and Environmental Contexts and Public Health Response
• Vector-borne Diseases
• Viruses
• Other infectious disease issues, including basic research on pathogens and disease prevention and treatment

Bacteria Environmental Sensing (Quorum Sensing)

Rahul V. Kulkarni, assistant professor of physics, conducts research on “quorum sensing” – the regulation of gene expression as a function of cell density. His research focuses on the integration of computational analysis and collaboration with experiments to discover novel components and achieve a more fundamental understanding of quorum-sensing networks in bacteria. His group has computationally discovered and experimentally verified novel genes called small RNAs that play a critical role in the quorum-sensing pathway and in regulating virulence. Considerable research suggests that many virulent bacteria can be rendered nonvirulent by the inhibition of their quorum-sensing pathways. Therefore, research into quorum sensing may provide a novel means of treating many common and damaging bacterial infections without the use of antibiotics. Furthermore, biotechnological approaches designed to exploit beneficial quorum-sensing processes may prove useful in improving industrial-scale production of natural or engineered bacterial products. Thus, the study of quorum-sensing is important from a basic science perspective as well as for its applications to medicine and biotechnology. More about Rahul V. Kulkarni.

Ann M. Stevens, associate professor of biological sciences, works in the general field of molecular microbiology with an emphasis on bacterial environmental sensing and gene regulation. The majority of the research projects focus on the phenomenon of bacterial quorum sensing, a mechanism whereby bacterial cells communicate with one another through the use of small molecules called autoinducers. By understanding this mode of bacterial gene regulation, methods to manipulate it in ways beneficial to society may be discovered. Her group studies the quorum sensing systems of three different bacteria, one that establishes symbiotic/beneficial relationships with animals, one that is an important plant/corn pathogen, and one that is free-living in the environment. In a separate project, she is exploring the development of antibiotic resistance in environmental bacteria that are exposed to stress from common chemical contaminants. More about Ann Stevens.

Zhaomin Yang, associate professor of microbiology in biological sciences, addresses how organisms as small as bacteria manage to sense and respond to environmental changes to either thrive in particular niches or to result in tremendous human suffering and misery. The lab uses the gram-negative soil bacterium Myxococcus Xanthus as a model and asks, how does this bacterium see, smell, or feel the changes in their surroundings and how do the cues they perceive lead to changes in their behavior and metabolism? More about Zhaomin Yang.

Food Safety

Renee Boyer, assistant professor of food science and technology and Extension specialist, studies pre- and post-harvest interventions to enhance the safety of fresh and fresh cut fruits and vegetables, specifically mechanisms for attachment and persistence of pathogenic bacteria on produce items; internalization of Salmonella and/or E. coli O157:H7 into tomatoes and leaf lettuces, and the use of high pressure processing to inactivate pathogenic bacteria on produce. More about Renee Boyer.

Joseph D. Eifert, associate professor of food science and technology and Extension specialist, develops methods to prevent bacterial foodborne pathogens from contaminating poultry processing plant environments and reduce the level of these pathogens on live birds and finished products; and determines ways to improve the microbiological quality and shelf life of ready-to-eat poultry products and fruits and vegetables through design of appropriate microbiological sampling techniques and sampling plans. More about Joseph D. Eifert.

George J. Flick Jr., University Distinguished Professor in food science and technology, is focused on improving the efficiency of unit processing operations in fish and shellfish firms, including chemical and microbial food safety, unit processing operations for aquatic food and industrial product production, product development, and quality assurance and control. Researchers in his lab are working on the effect of alternative processing operations (high pressure, irradiation, thermal energy) on survival of the parasite, Cryptosporidium parvum, in oysters; the effects of harvesting, processing, and distribution on the formation of histamine and other biogenic amines in major commercial mid-Atlantic fish species; the presence and dynamics of Listeria monocytogenes and other Listeria species in ready-to-eat fish and shellfish products; and the effects of thermal processing on the quality and safety of pasteurized blue crab meat. More about George J. Flick Jr..

Stephen Melville, associate professor of microbiology in biological sciences, studies the bacterial pathogen Clostridium perfringens, which causes gas gangrene and food poisoning. It colonizes the human colon very efficiently and he is studying the mechanism it uses to attach itself to host cells. These bacteria appear to use a type of pili, hair-like structures that stick out of the surface of the bacterium, to attach to host cell surfaces. They not only use the pili for attachment, but they can also use them to move along the surface of human cells with a gliding motion. Melville’s research centers on the mechanism of pili assembly and function, with the hope that he can use the results to develop strategies to limit the ability of the bacterium to colonize human tissues. C. perfringens also secretes large quantities of powerful toxins that kill host cells. The other main area of research in his lab is to understand how the bacterium regulates the synthesis of these toxins since they are the major mediator of disease. Strategies that prevent the bacterium from making or secreting toxins would be a useful approach to cure the diseases caused by C. perfringens, which often do not respond to antibiotics alone. More about Stephen Melville.

Monica Ponder, assistant professor of food science and technology, studies the epidemiology and ecology of food-borne pathogens. The ability of a human pathogen to colonize a plant is influenced not only by environmental stresses such as temperature, exposure to UV radiation, and dehydration, but also by the interaction with the native species of plant microbiota. Ponder is working to identify antagonistic or permissive members of the produce microbiota in order to develop strategies that make use of beneficial bacteria to control growth and survival of pathogens on produce allowing for design of effective packaging and control procedures post-harvest. She is also looking at differences in survival, host specificity, or expression of virulence genes using a combination of molecular subtyping methodologies and comparative molecular techniques in order to enhance the ability to develop intervention strategies and interpret subtyping data used to trace food-borne outbreaks. More about Monica Ponder.

Robert C. Williams, assistant professor of food science and technology, studies pathogen control in fresh and minimally processed fruits and vegetables, fruit juices, and ready-to-eat foods, including the application of various processing techniques, such as ozone, UV light, and in-package pasteurization, and antimicrobial treatments for bacterial pathogen reduction in products intended to be consumed with little or no further processing by the consumer.More about Robert C. Williams.

Social and Environmental Contexts and Public Health Response

Stephen Eubank, deputy director of the Network Dynamics and Simulation Science Lab of the Virginia Bioinformatics Institute and adjunct professor of physics, is developing interaction-based modeling, simulation, and associated analysis, experimental design, and decision support tools for understanding large biological, information, social, and technological systems. One application is the National Institutes for Health Modeling Infectious Disease Agent Study (MIDAS) network. Eubank’s project models the spread of disease transmitted from person to person in urban areas, allowing for the assessment of prevention, intervention, and response strategies by simulating the daily movements of individuals within an urban region. The models allow the user to specify the effects in detail of a pathogen on a specific person, and to assign different effects to various people based on demographic characteristics. Through MIDAS, Eubank’s group has influenced national policy on preparing for an influenza pandemic. Through related work for the Department of Defense, he is supporting the development of mitigation strategies for military populations in a pandemic. In conjunction with population mobility models it can represent behavioral reactions to an outbreak, including official interventions. As part of a National Science Foundation Human Social Dynamics grant, NDSSL is using this model to study the co-evolution of social networks and disease transmission networks. Other projects at NDSSL relevant to infectious disease include creating spatial models of vector-borne disease epidemiology and applying them to malaria in sub-Saharan Africa, and modeling the human immune system in detail to study the dynamics of HIV recombination within an individual. More about Stephen Eubank.

Bernice L. Hausman, professor of English, is looking at historical, cultural, and discourse-based interpretive methods, primarily addressing figurations of mothers in public health debates, medical advice genres, and the mass media, to reveal how very real concerns are nevertheless imagined and experienced through ideological constructions of maternity. More about Bernice L. Hausman.

Vector-Borne Disease

Zach Adelman, assistant professor of entomology affiliated with the Fralin Life Science Institute seeks to understand, at the molecular and genetic level, how viruses infect, replicate, and are transmitted by mosquitoes to humans and the mosquito immune response to these viruses. Using this information to design and implement new methods of controlling or preventing mosquito-borne viral disease outbreaks includes using genetics to block the mosquito’s ability to transmit viruses, and the development of new diagnostic tools to identify mosquitoes which are more likely to participate in an outbreak. More about Zach Adelman.

Jeffrey R. Bloomquist, professor of pharmacology and toxicology in the Department of Entomology, is developing new and safer chemicals for use in human disease control and agriculture. His research includes studies on both mammals and insects to design chemicals with good selectivity and which are focused on the interactions of small organic molecules with protein receptors found on cell membranes. These organic molecules can be drugs, peptides, neurotransmitters, or insecticides. Most of his research is focused on the mechanisms of how these compounds are toxic to the nervous system, along with investigation into the mechanisms of insecticide resistance. He studies of whole animal toxicity, effects on the nervous system, and actions on proteins at the biochemical level. More about Jeffrey R. Bloomquist.

Paul Carlier, professor of chemistry, leads a large group of postdoctoral associates and graduate students in the synthesis of species-specific enzyme inhibitors and receptor ligands. Since human and insect proteins of identical physiological function often share only 50 percent identity in their amino acid composition, it is possible to design compounds that dramatically interfere with the function of insect proteins while leaving human proteins largely unaffected. A number of techniques are used in the design of these compounds, including structure-based drug design, click chemistry, and traditional lead optimization. In collaboration with Jeffrey Bloomquist and Sally Paulson, and colleagues at Molsoft, Carlier has prepared highly effective contact poisons for the malaria mosquito, Anopheles gambiae, that show 100-fold selectivity for mosquito acetylcholinesterase over the human enzyme. More about Paul Carlier.

Carlyle C. Brewster, associate professor of entomology, uses satellite remote sensing, geographic information systems (GIS), and spatial analyses to study vector population dynamics and the ecological determinants of disease transmission by the vectors. His efforts have included studies of vector populations throughout regional landscapes in relation to environmental variables with the aim of developing targeted surveillance programs. Brewster, Sally Paulson, and others have been looking at the incidence of canine infection with LAC to determine whether dogs might be used as sentinels for La Crosse (LAC) virus, the leading cause of pediatric encephalitis in the United States. Within the past decade, there has been a rapid emergence of the virus and its primary mosquito vector in several southeastern states, including Virginia, complicated by the possible involvement of two non-native species of mosquitoes that have reached the U.S. and by the inability to directly assess mosquito populations over large areas. More about Carlyle C. Brewster.

Michael Klemba, assistant professor of biochemistry, is working on anti malaria strategies. The malaria parasite, a single-cell organism, causes disease as it reproduces within human red blood cells. As it grows, the parasite consumes its host cell from the inside, devouring most of the red blood cell’s oxygen-carrying protein, hemoglobin. His research aims to understand how the malaria parasite achieves this catabolic feat. His focus is enzymes called peptidases, which chop hemoglobin into small pieces, and ultimately, into its amino acid building blocks. By understanding how these peptidases work, he hopes to discover chinks in the parasite’s armor that could be exploited for the development of peptidase inhibitors that have anti-malarial activity. More about Michael Klemba.

Korine N. Kolivras, assistant professor of geography, studies the social and environmental aspects of disease emergence. Specifically, her work evaluates the ways that environmental variability influences the spatial and temporal patterns of vector-borne diseases, and how the social issues of sanitation and water quality relate to health and disease emergence potential. She looks at how climate variability and change impact the range of vectors, with areas expanding or contracting based on temperature and precipitation patterns at regional scales, and at fine scales, how individual behaviors and local environmental characteristics can result in the creation of vector habitat in a community and around a home. She uses geospatial technologies, such as remote sensing and geographic information systems (GIS), to evaluate the relationship between disease emergence and the underlying human or environmental factors. More about Korine N. Kolivras.

Jianyong Li, associate professor of biochemistry, is part of an international group that has determined the structure of a protein that is responsible for the production of xanthurenic acid (XA) in Anopheles gambiae, the malaria carrying mosquitoes. XA plays a key role in the sexual reproduction of the malaria parasite, Plasmodium falciparum, in A. gambiae. Interfering with the formation of XA could be an avenue for development of anti-malarial agents. More about Jianyong Li.

Kevin Myles, assistant professor of entomology affiliated with the Fralin Life Science Institute, focuses on understanding the interactions between the virus and vector that result in the establishment and persistence of non-pathogenic infections in the mosquito host. The information obtained from these studies will improve our ability to predict and prevent arboviral disease epidemics. In addition, a strategy that would replace natural populations of mosquitoes with genetically modified mosquitoes is currently being investigated for controlling these important pathogens. Understanding the genetic components controlling the pathogenic potential of arboviruses may be useful in such a strategy. For example, it may be possible to create mosquitoes that would be rapidly killed when infected with an arbovirus. Thus, in the future, a more complete understanding of how persistent arbovirus infections are established in the vector host may provide a basis for human intervention of arboviral disease transmission. More about Kevin Myles.

Sally Paulson, associate professor of entomology, is doing research directed at the La Crosse encephalitis virus, the most common and important endemic mosquito-borne disease of children in the United States. Her group is looking at the role of newly introduced mosquito species, Aedes albopictus and Ochlerotatus japonicus, in the transmission of disease, specifically in Southwest Virginia. She is also studying the bionomics, or relationship to the environment, in Southwest Virginia of the Culex mosquito, which carries West Nile virus. More about Sally Paulson.

Igor V. Sharakhov, assistant professor of entomology, is doing research to understand the role of genome rearrangements in mosquito evolution, adaptation, and ability to transmit malaria parasites. The ultimate goal of this research is to develop a novel genomics-based approach for vector control. More about Igor V. Sharakhov.

Zhijian Jake Tu, associate professor of biochemistry, is using modern genomics and bioinformatics tools to study the basic genetics and physiology of mosquitoes with the long-term goal of reducing the burden of vector-borne infectious diseases. His research program covers three areas. The first is mosquito transposable elements (TEs), which are mobile genetic elements that have the ability to replicate and spread in the genome. Objectives are to understand the fundamental biology of TEs and their genomic and evolutionary impacts as well as to explore the applications of TEs as molecular tools to manipulate mosquito genomes for the purpose of interrupting transmission of pathogens. Second, the group is conducting comparative genomics on a range of mosquitoes to provide high-resolution identification of regulatory elements, uncover gene expansions/loss/rearrangements, and reveal correlations between these genetic changes and biological adaptations which are being tested experimentally. Finally, the team has identified a number of mosquito-specific microRNAs (miRNAs), which are a novel class of gene modulating molecules that modulate the expression of cellular genes by binding to cognate mRNAs for cleavage or translational repression. Several of these have been shown to be key regulatory molecules during embryonic development, stem cell division, neurogenesis, heart development, haematopoietic cell differentiation, and cell death. miRNAs are also implicated in cancer and control of viral infection. The level of several miRNAs changed two- to three-fold in mosquitoes after a blood meal, according to our preliminary miRNA array analyses using whole body samples. Tu is testing the hypothesis that a small number of miRNAs are among the key factors regulating tissue and temporal specific response to blood feeding during the mosquito gonotrophic cycle and other miRNAs may be involved in mosquito-pathogen interactions. More about Zhijian Jake Tu.

Jinsong Zhu, assistant professor of biochemistry, is exploring strategies to control emerging or resurging mosquito-borne diseases. An effective approach is to minimize the risk of infection by reducing mosquito populations. In the face of the growing pesticide resistance detected in field populations of mosquito vectors, new environmentally safe chemicals are needed to kill mosquitoes at various developmental stages. Understanding how mosquito endogenous growth regulators exert their function will facilitate discovery of chemicals that repress or block the normal growth and development of the mosquito. Another promising approach is to use genetic engineering to eliminate or decrease the vector competence of mosquitoes. Some mosquitoes are refractory to infections of pathogens in nature. Comparing gene expression of refractory and susceptible mosquitoes in response to pathogen infections will shed light on the molecular nature of mosquito-pathogen interactions and provide invaluable information on what protein factors in mosquitoes are suitable for genetic intervention to adversely affect the pathogens. More about Jinsong Zhu.

• Also see the Vector-Borne Disease Research Group.

Viruses

Tanya LeRoith, assistant professor of biomedical science, is doing research to develop animal models of infectious disease. Her laboratory is interested in the immunopathogenesis of hepatitis E virus, as well as characterizing the immune response to porcine reproductive and respiratory virus (PRRSV), and porcine circovirus 2 (PCV-2).

X.J. Meng, M.D., Ph.D., and professor of molecular virology in the Virginia-Maryland Regional College of Veterinary Medicine, does research focused on the development of vaccines against emerging, re-emerging, and zoonotic viral diseases of public health and/or economic importance. His laboratory studies multiple virus systems including the hepatitis E virus (the causative agent of human hepatitis E, which is an important human pathogen), Type 2 porcine circovirus (which is an emerging and economically important swine pathogen), and porcine reproductive and respiratory syndrome virus (another economically important swine pathogen). This research has recently led to the development and licensure of the first United State Department of Agriculture fully-licensed vaccine, “Suvaxyan® PCV2 One Dose™, against a deadly global swine disease. This vaccine will save the global swine industry millions of dollars each year from loss caused by the disease. More about X.J. Meng.

P. Christopher Roberts, associate professor of virology with the Center for Molecular Medicine and Infectious Diseases in the Virginia-Maryland Regional College of Veterinary Medicine, studies influenza virus and other respiratory pathogens. A major focus is to develop newer, more protective vaccines that provide long-lasting protection to humans and animals against emerging viral pathogens, particularly influenza. By developing vaccines targeting the elderly, Roberts’ group hopes to significantly reduce health care costs associated with respiratory viruses. The program is also seeking new ways to utilize naturally occurring viruses as a means to selectively target cancer cells within the body and destroy them. He and Eva Schmelz, associate professor of human nutrition, foods, and exercise, are partnering with Dennis Scribner, gynecological oncology section chief at Carilion Clinic, on characterization of early defects in immunosurveillance mechanisms during ovarian cancer progression. More about P. Christopher Roberts.

Lijuan Yuan, assistant professor of biomedical sciences and pathobiology in the Virginia-Maryland Regional College of Veterinary Medicine, studies rotaviruses, which are the leading cause of severe gastroenteritis in infants and children worldwide. Probiotics, such as Lactobacilli, have been shown to reduce the severity of rotavirus diarrhea; however the immunologic mechanisms have not been clearly defined. Colonization of the human intestine with commensal microbes is hypothesized to drive the maturation of the mucosal immune system during neonatal life, but the mechanisms are unknown. A goal of her laboratory is to define the impact of colonization of the intestine by probiotic commensal microbes on development of the mucosal immune system and innate and adaptive immune responses to enteric virus infections and to clarify the immunological mechanisms involved using gnotobiotic pigs colonized with two Lactobacillus strains used in the food industry. More about Lijuan Yuan.

Other Infectious Disease Issues

Including basic research on pathogens and disease prevention and treatment

Lisa Belden, assistant professor of biological sciences, studies how biodiversity influences parasites and pathogens in natural systems. She is examining two different systems. The first is a host-parasite system involving amphibian and snail hosts and a trematode parasite to determine how changes in the species composition of ponds can influence infection in tadpoles, as well as how features of the landscape influence transmission of the parasite. The second system involves the normal bacterial community that lives on the skin of amphibians. She is examining whether beneficial bacteria can prevent infection of the skin with pathogens and whether environmental stressors can alter the outcome of these species interactions. Ecological interactions between species and ongoing environmental changes likely play key roles in the emergence of many diseases in both wildlife and human populations. More about Lisa Belden.

Stephen M. Boyle, professor of microbiology in the Virginia-Maryland Regional College of Veterinary Medicine, studies the immune system of animals and humans and the creation of vaccines that will signal the immune system to produce antibodies and cells that prevent a pathogen from causing disease. His laboratory is working to improve a vaccine (Brucella abortus RB51™), created at Virginia Tech and approved by the United States Department of Agriculture in 1996, to prevent the disease called brucellosis that occurs in animals and humans. The vaccine improvement is using the original vaccine as a platform to protect against other diseases, such as anthrax. The impact of such a potent vaccine will reduce the cost of producing healthy livestock and health care by preventing the spread of diseases from animals to humans. More about Stephen M. Boyle.

Dennis R. Dean, professor of biochemistry and director of the Fralin Life Science Institute, studies nitrogen fixation and the critical oxidation and reduction reactions that occur at iron atoms that are found in complexes called iron-sulfur clusters. The biological formation of iron-sulfur clusters is different for different organisms. For this reason, and because formation of iron-sulfur clusters is required for an organism to survive, disruption of this process in pathogenic organisms provides an ideal target for the development of therapeutic agents. More about Dennis R. Dean.

Will Eyestone, professor of large animal clinical sciences, is working on Bovine Spongiform Encephalopathy (BSE), an infectious and incurable disease that is a threat to agriculture and human health. The agent of BSE is known as the pathogenic prion (PrPSc) and is believed to originate from the autocatalytic conversion of the cellular prion protein (PrPC). The researchers sought to characterize PrPC expression in several bovine tissues. They have determined that PrPC expression is not confined to the nervous system but is widely present in peripheral tissues of the bovine. Further studies of PrPSc infectivity may elucidate the role of these tissues in BSE pathogenesis and transmission. More about Will Eyestone.

Joseph O. Falkinham III, professor of biological sciences, is testing drugs for treating emerging pathogens (e.g., Mycobacterium), antibiotic-resistant pathogens (e.g., Enterococcus, Staphylococcus aureus, and Methicillin-resistant S. aureus, or MRSA), and fungal pathogens (e.g., Candida spp.). Preliminary data indicate that several members of a novel class of drugs caused an inhibition of growth at microgram concentrations against such pathogens as S. aureus, MRSA, and C. albicans. These new antibiotics could potentially prevent and treat topical infections, such as vaginitis (C. albicans), and prevent nasal colonization and transmission of S.aureus and MRSA. Investigations may be extended to include designing antibiotics for treating more serious systemic infections. Research is also being done to discover the mechanism of antimicrobial action of these novel antibiotics, whicy will lead to the identification of new drug targets in pathogenic bacteria, mycobacteria, and fungi. More about Joseph O. Falkinham III.

Dana M. Hawley, assistant professor of biological sciences, is looking at how pathogens are colonizing novel hosts with increasing frequency due to global agricultural traffic and habitat alteration and investigating the ecological and evolutionary mechanisms that underlie pathogen susceptibility, from single host individuals to multi-host communities. She is currently studying disease dynamics in the context of two broad frameworks: 1) genetic and species-level diversity, and 2) environmental and social stressors. She approaches disease ecology from a multi-disciplinary perspective in order to understand how stress, genetics, social behavior, community composition, and environmental context interact dynamically to influence host disease susceptibility and pathogen transmission. More about Dana M. Hawley.

Marcy Hernick, assistant professor of biochemistry, is interested in the characterization of enzyme drug targets in Mycobacterium tuberculosis and in the development of inhibitors against these enzymes as potential anti-tuberculosis agents. The development of new drugs for the treatment of tuberculosis (TB) is of increasing importance because of the emergence of drug resistant forms of TB, specifically MDR- and XDR-TB. Current efforts in her laboratory are focused on the mycothiol biosynthetic and detoxification pathways. She uses a variety of biochemical and biophysical techniques (kinetic and thermodynamic studies) to characterize the mechanisms and molecular recognition properties of these enzymes. She is also using organic chemistry to synthesize libraries of small molecules that may function as inhibitors of these target enzymes. Information gained regarding enzyme mechanism and recognition will be used for the optimization of potent and specific enzyme inhibitors in the future. More about Marcy Hernick

Thomas J. Inzana, the Tyler J and Francis F. Young professor of bacteriology, is partnering with Tom Kerkering, infectious disease section chief with Carilion Clinic; J.R. Heflin, professor of physics at Virginia Tech; and A.B. Bandara, research assistant professor of biomedical sciences and pathobiology in the Virginia-Maryland Regional College of Veterinary Medicine, on development of nanoscale optical fiber biosensor assays to detect and differentiate Staphylococcus aureus and Methicillin-Resistant S. aureus (MRSA).

He also studies Francisella tularensis, a Category A bacterial pathogen responsible for tularemia. There is no approved vaccine for tularemia, and no approved rapid, non-culture diagnostic test. Due to the threat of bioterrorism, improved vaccines, diagnostic tests, and therapeutics are a high priority for F. tularensis and other select agents. Inzana’s laboratory has isolated a novel glycolipid from F. tularensis that stimulates an immune response. The lab has also identified the putative capsule DNA locus and made a mutant that may be unable to export this glycolipid. Antibodies to this glycolipid are being raised for use in diagnostic tests.

The Inzana lab is also studying Histophilus somni, which is responsible for a wide variety of systemic diseases in cattle, including meningitis, myocarditis, pneumonia, and septicemia. H. somni produces an exopolysaccharide and an excellent biofilm. Current work is focused on biofilm formation in the natural bovine host, and the use of this system as a model for biofilm infections in humans. More about Thomas J. Inzana.

Biswarup Mukhopadhyay, assistant professor at the Virginia Bioinformatics Institute, and Endang Purwantini, senior research associate, are doing research to identify new cellular targets in Mycobacterium tuberculosis, the causative agent of TB, for the development of new therapeutics for TB. Approaches involve laboratory-based microbial genetics, molecular biology, and biochemistry investigations, and a site-based study. The site-based study utilizes clinical strains of M. tuberculosis isolated at the Rotinsulu Pulmonary Hospital (Bandung, Indonesia); this work represents collaboration between the Virginia Bioinformatics Institute, the Institut Teknologi Bandung, and Rotinsulu Pulmonary Hospital. The goal is to determine the genetic and biochemical basis for the development of more virulent and MDR or XDR strains of M. tuberculosis. The project is based on the hypothesis that population lifestyles (economic status, mobility, and environment) and treatment methodologies determine the immune system of a patient and chemical environment within the infected immune cells and promote changes in the genome of the pathogen which lead to increased virulence and drug resistance in TB. More about Biswarup Mukhopadhyay.

Isis Mullarky, assistant professor of dairy science, is working to identify new mechanisms for controlling the bacteria Staphylococus aureus, a leading cause of community acquired infections, surgical site infections, bovine mastitis, and human skin infections, which has multi-drug resistant strains. S. aureus causes disease in the human by producing toxins and by invading epithelial cells (EC). EC are implicated in the production of coagulatory proteins to maintain hemostasis. Mullarky’s goal is to understand the basic immune and coagulatory responses of EC during infection with S. aureus. She is using a bovine model that allows a detailed history of infection status and a cataloged collection of the S. aureus strains that caused these infections. Her group hopes to identify antigens that stimulate immune memory and are candidates for vaccine development. More about Isis Mullarky.

David L. Popham, associate professor of biological sciences, Departmental Microbiology Group coordinator, and chair of the Interdepartmental Microbiology Graduate Program, studies two aspects of bacterial growth and survival that have great effects on the ability of bacteria to cause disease: the formation of their peptidoglycan cell wall and the formation of dormant spores. Synthesis of the bacterial cell wall has traditionally been the best target for antibiotic development. It is still considered an outstanding target since it is highly conserved across virtually all bacterial species. The group’s studies on the precise roles of a variety of proteins in cell wall synthesis will contribute to the rational design of new classes of antibiotics. Formation of spores allows certain bacteria to survive in and invade habitats unavailable to other species and, thus, to affect human health. The spores of Bacillus anthracis are the infectious agent for anthrax, and the sporulation by Clostridium perfringens is required for this species to cause both food poisoning and gangrene. The Microbiology Group studies spore structure in both of these species, specifically the unique spore peptidoglycan wall, in order to determine how this structure contributes to the ability of spores to survive high heat and other treatments that normally kill all other cell types and how this structure is degraded when the spores are ready to germinate and cause disease. More about David L. Popham.

Webster L. Santos, assistant professor of chemistry, is interested in using chemistry to understand biological processes. The primary focus is the development of chemical toolboxes to address problems in biology. Current work is aimed at discovering and developing novel molecular entities that can be used as probes or as therapeutics for disease states (Parkinson’s and Alzheimer’s disease) that are not efficiently addressed using conventional small molecule drugs. The Santos group is also interested in the search for new strategies in combating infectious diseases such as malaria and influenza. In organic chemistry, he is employing a chemical biology approach in evolving nucleic acid polymers such as RNA to discover molecular scaffolds that can catalyze chemical reactions that are environmentally friendly. One goal is to use modular RNA to perform the total synthesis of natural products, where one product can arise from a complex pool of starting materials. More about Webster L. Santos.

Florian Schubot, assistant professor of biological sciences, studies the bacterium Pseudomonas aeruginosa, an opportunistic pathogen that causes a number of life threatening infections in predisposed individuals. For instance, chronic lung infections by P.aeruginosa are the major cause of mortality in cystic fibrosis patients. Generally, P.aeruginosa infections can be acute or chronic. The hallmark of acute infection is the type III secretion system, a syringe-like channel employed by P.aeruginosa to export a number of virulence factors that suppress the host immune response. The characteristic feature of chronic infections is the formation of protective biofilms that shield the bacterial colonies from the host immune system and impart antibiotic resistance. Schubot’s group is studying the regulatory mechanisms that control both the type III secretion system and biofilm formation, combining structural biology, biochemical studies, and microbiology. The long term goal is to aid the development of new therapeutic options against P.aeruginosa through discovery of novel anti-microbial agents. More about Florian Schubot.

Pablo Sobrado, assistant professor of biochemistry, conducts research on the mechanism and regulation of enzyme action, structure-function of enzymes, and identification of novel kinase substrates. Projects related to infectious disease include 1) biosynthesis of the siderophores produced by the human pathogens Mycobacterium tuberculosis, Aspergillus fumigatus, and Yersinia pestis; 2) understanding Galactofuranose (Galf) an important component of the cell surface of several pathogenic bacteria, protozoan, fungi and mycobacterium that is not present in humans, making its biosynthetic pathway a target for new antibiotics; and 3) determination of the activity, regulation and identification of interacting partners of mammalian casein kinase 1 splice variants and characterization of CK1 as a target for anti-parasitic chemotherapy. More about Pablo Sobrado.

Nammalwar Sriranganathan, professor of microbiology in biomedical sciences and pathobiology, is developing and testing vaccines against intracellular pathogens. Researchers in his lab are using a current USDA approved cattle vaccine, B. abortus RB51, developed at the Center for Molecular Medicine and Infectious Diseases at Virginia Tech, as a vector to express protective antigens against other infectious agents. Three candidate RB51-NC recombinant vaccines have shown promise. Flagellin, a filament protein that forms bacterial flagellum, appears to function as an excellent adjuvant for the intranasal route of vaccine delivery and induces high levels of antibodies against F1. It has been found to provide protection against an aerosol challenge of Yersinia pestis, the causative agent of bubonic plague, at 150 times the lethal dose. Similar studies are being conducted using the V antigen as the initiator. Some of the F1/V constructs, with flagellin as the adjuvant, appear to provide protection. The group is also studying the effect of aging on the immune response against the intracellular pathogen B. abortus and initiated efforts to develop targeted drug delivery against intracellular pathogens. More about Nammalwar Sriranganathan.

Yasuhiro Suzuki, associate professor of molecular immunology in the Department of Biomedical Sciences and Pathobiology in the Virginia-Maryland Regional College of Veterinary Medicine, whose laboratory has been investigating the mechanism of host-pathogen interactions in infection with Toxoplasma gondii, an obligate intracellular protozoan parasite. The recent focus of research is the molecular immunopathogenesis of cerebral toxoplasmosis. Toxoplasmic encephalitis has been a major opportunistic infectious disease in immunocompromised patients, such as those with AIDS and organ transplant recipients.

John J. Tyson, University Distinguished professor of biological sciences, studies the cell division cycle, the sequence of events whereby a growing cell makes new copies of all its parts and divides them, more-or-less, evenly between two daughter cells so that each daughter contains all the information and machinery necessary to repeat the process. Mistakes and problems in cell growth and division underlie many human health problems, including cancer, tissue regeneration, and infectious diseases. A life scientist must understand the molecular components of the cellular control system and how they interact in order to develop new drugs and therapies for the infirmities that stem from faulty controls. His research group builds mathematical models of these control systems in order to better understand the complex molecular interactions within living cells and how they are perturbed in diseased states.  More about John J. Tyson.