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PROFESSOR COLLEEN JONSSON Zeroing in on infectious disease The Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases at the University of Louisville is dedicated to conducting basic and translational research into infectious diseases, with the help of the Regional Biocontainment Laboratory’s Shared Resources Services THROUGH ITS IMPORTANT and timely work, the Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases (CPM) aims to improve human health by developing effective diagnostic biomarkers, vaccines, antivirals and therapeutics for emerging, neglected rare infectious diseases. It also aims to protect national security by guarding against biothreats. The CPM is well on its way to meeting these goals thanks to the innovative work of the researchers it supports. Colleen Jonsson, PhD, Director of the CPM, Professor of Microbiology – as Director of the CPM, Jonsson is in charge of guiding and working towards the goals of the Center and its members. In the laboratory setting, Jonsson’s work uses in vitro and animal models to address virushost interaction. Her research programme is focused on the recent 2009 H1N1 influenza virus and hantaviruses. William E Severson, PhD, Director of the Regional Biocontainment Laboratory (RBL)’s Shared Resources Services – the new RBL is an integral addition to the CPM that has Biosafety Level 2, Biosafety Level 3 and Select Agent facilities that are utilised for basic and applied research concerning the creation of biomarkers, vaccines, antivirals and therapeutics for infectious diseases. As the leader of the new RBL, Severson is directing its dedicated staff to ensure the lab’s state-of-the-art equipment is a useful cornerstone in translational partnerships, both internally and externally. Donghoon Chung, PhD, Assistant Professor of Microbiology – Chung’s laboratory studies the replication mechanism of alphaviruses, which can be found across the globe, and infect humans and equines via mosquitoes. To study the molecular mechanism in an explicit way, his lab is using high-throughput screening techniques to discover small molecules that probe the biology of alphaviruses. He is also interested in developing these molecules into therapeutics for viral diseases. Matthew Lawrenz, PhD, Assistant Professor of Microbiology – Lawrenz’s laboratory is defining the early events that occur during plague infection (a re-emerging disease and potential bioterrorism weapon) to discover how to better prevent and treat human plague. Specifically, his lab is studying how Yersinia pestis, the bacterium that causes the plague, colonises its human host. His goal is to use this information to design better vaccine and therapeutic candidates for the plague. Michael Hughes, MD, Director of Pancreas Transplantation, Assistant Professor of Surgery – Hughes’ laboratory is focused on chronic infection with the Hepatitis C virus (HCV – a leading cause of cirrhosis, liver failure and liver transplantation worldwide). Few treatment options have existed for HCV until recently. With multiple new agents coming to market to treat HCV infection, Hughes is working to characterise viral adaptation, mutation and evolution during treatment. Jonathan Warawa, PhD, Assistant Professor of Microbiology – Warawa’s laboratory is studying bacterial respiratory pathogens, with a special focus on the biodefense pathogen Burkholderia pseudomallei. The pathogen causes a fatal septicaemic disease. It is intrinsically resistant to several classes of antibiotics and has been identified as a Tier 1 Select Agent pathogen since it is a potential bioweapon. Therefore, the lab’s research into the respiratory disease the pathogen causes is significant for treating the naturally occurring disease and for biodefense preparedness. Igor Lukashevich, MD, PhD, Professor of Pharmacology – Lukashevich’s laboratory covers two major areas: pathogenesis of viral haemorrhagic fevers (VHF) and vaccine research and development. The lab has achieved great success so far with the reassortant ML29, a vaccine candidate against Lassa fever, the most prevalent VHF in Africa. The ML29 is safe and effective as a preventive vaccine and a post-exposure treatment. Haixun Guo, PhD, Assistant Professor of Radiology – Guo’s laboratory leads the radiochemistry and molecular imaging probe development programme. It focuses on developing novel positron emission tomography and single photon emission computed tomography probes to image inflammation and infection. Yousef Abu Kwaik, PhD, Bumgardner Chair in Molecular Pathogenesis, Department of Microbiology and Immunology – Abu Kwaik’s laboratory is examining cell and molecular biology of the intracellular infection from Legionella and Francisella. The research aims to uncover potential targets for therapy and prevention of diseases caused by the two organisms. Jill Steinbach, PhD, Assistant Professor of Bioengineering – Steinbach’s programme is initiating research into designing and developing drug and gene delivery vehicles and new nanomaterials that provide more efficacious prophylactics/therapeutics for sexually transmitted infections, including acute and chronic (latent) infections. WWW.RESEARCHMEDIA.EU 35 PROFESSOR COLLEEN JONSSON Decimating infectious diseases Researchers based at the Center for Predictive Medicine for Biodefense and Emerging Diseases at the University of Louisville, Kentucky, are using pioneering methods and shared resources to address critical research questions surrounding rare, neglected, emerging and re-emerging pathogens IN THE LAST quarter of the 20th Century, many of the pathogens underlying previously eradicated diseases have re-emerged as deadly foes once more. Even today, they are adapting, changing and developing a resistance to the drugs used to treat them. Additionally, new, previously unidentified pathogens have emerged from the environment. The Center for Predictive Medicine for Biodefense and Emerging Diseases (CPM) at the University of Louisville (UofL) in Kentucky, USA, is performing cutting-edge research to reverse and overcome these trends. The Center’s goal is to engage in exceptional translational research that will one day lead to diagnostic biomarkers, vaccines, antivirals and therapeutics for new and re-emerging pathogens and biothreats. The CPM’s work, which is directed by Dr Colleen Jonsson, is not only important to human health, but also to US national security, as its scientific experts and facilities are ready to serve in the event of a pandemic or bioterrorism emergency. THE CENTER’S RESEARCH The faculty who work in the CPM focus their attention on four different areas: rare, neglected, emerging and re-emerging pathogens research. For example, Drs Michael Hughes and Jill Steinbach are researching Regional Biocontainment Lab. 36INTERNATIONAL INNOVATION the mechanisms of pathogen colonisation and invasion of host cells, while Drs Jonathan Warawa, Matthew Lawrenz and Yousef Abu Kwaik are studying the mechanisms of microbial virulence. Lawrenz is also examining pathogen replication in host cells, as is Dr Donghoon Chung. Finally, Jonsson herself is rolling up her sleeves to pin down the details of the host immune mechanisms that respond to and clear infection. The ultimate goal behind these endeavours is to identify new therapeutic targets through basic discovery research and to pair this work with translational research to develop new drug and vaccine candidates, whole live animal imaging probes and drug delivery systems. CROSSING DISCIPLINES FOR INNOVATIVE IDEAS A cross-disciplinary approach is crucial to the success of the CPM’s novel research. Sometimes these collaborations are forged solely within the Center, as the diversity of complementary expertise in microbiology, virology and radiology on hand means that the CPM can provide a bridge to connect multiple disciplines in one forum. “The cross-disciplinary approach of the CPM has opened several new avenues of research in my laboratory,” enthuses Lawrenz, who researches the plague at the CPM. “The opportunity to collaborate with cell biologists and experts in high-throughput biology within the CPM has allowed us to take unique approaches to studying hostpathogen interactions that we had not previously considered.” In fact, through his collaborations, Lawrenz was able to initiate the first genome-wide screen to identify host proteins that Yersinia pestis uses to survive within macrophages. However, just as often as not, CPM collaborations are happening not only across disciplines, but also across state and country borders. For example, CPM researchers are engaged in collaborations ranging from the Infectious Disease Department at the Cincinnati Children’s Hospital to the Pasteur Institute in Paris. INTRODUCING THE REGIONAL BIOCONTAINMENT LABORATORY A cross-disciplinary and collaborative approach is also central to the Regional Biocontainment Laboratory (RBL), which opened under the umbrella of the CPM in autumn 2010. The RBL stands as a critical regional, national and international shared resource for scientists engaged in translational research with lethal pathogens requiring Biosafety Level 3 (BSL-3) containment. The RBL was built as one of 11 BSL-3 facilities that the National Institute for Allergy and Infectious Diseases commissioned after the 9/11 terrorism attack and anthrax mailings in 2001. Due to the lethal nature of the pathogens under examination in the RBL, it has been built to the most rigorous standards, and it is certified for use by the Centers for Disease Control and Prevention and US Department of Agriculture Select Agents. In addition to being built with safety in mind, the RBL received recognition for its ‘green design’. The US Green Building Council awarded it the silver level from the Leadership in Energy and Environmental Design programme, which encourages the energy efficient, environmentally friendly design of modern buildings. SHARING RBL RESOURCES In 2011, the CPM created a Shared Resources Service Center to support internal and external users of the RBL. The Shared Resources within the RBL are under the direction of Dr William Severson. He works collaboratively with users from UofL, external academics and commercial INTELLIGENCE UofL CPM Regional Biocontainment Laboratory ABSL-3. CENTER FOR PREDICTIVE MEDICINE FOR BIODEFENSE AND EMERGING INFECTIOUS DISEASES OBJECTIVES New and re-emerging pathogens and the diseases they cause pose a continued threat to humanity, whether they stem from natural or intentional causes. The mission of the Center is to support basic and translational research to advance scientific understanding of these pathogens; and to promote the development of countermeasures for emerging and biothreat pathogens. PARTNERS Unites States Army Institute of Infectious Diseases • Western Kentucky University • Purdue University • Texas Tech University • NIH Rocky Mountain Laboratory • NIH Center for Infectious Disease Imaging, Harvard University • University of Kansas • Kansas State University clients to conduct their translational research utilising high-tech instruments – the Siemens PET/SPECT/CT tri-modality scanner, Caliper Life IVIS Spectrum and Zeiss LSM 710/LIVE 5 confocal microscope. Users have access to these instruments through five Core services: BioImaging, Immunology, Microbiology, Animal Models and High Throughput Biology (HTB). “The Shared Resources, especially the Animal Models Core, play an important role in the imaging probe development research. They enable us to evaluate the imaging probes for BSL-3 pathogens in vitro and in vivo,” states Dr Haixun Guo, who is Assistant Professor of Radiology in the UofL School of Medicine and an avid RBL Shared Resources user. PROVIDING A SERVICE Both the equipment and Cores assist its users with a number of otherwise impossible, timely or costly tasks. The HTB Core, for example, provides support for DNA sequencing, a quantitative reverse transcription polymerase chain reaction (qRTPCR), assay development and implementation and high-throughput screening of small molecule chemical and siRNA genome libraries. The BioImaging Core, on the other hand, makes use of the Siemens PET/SPECT/CT Trimodal to assist scientists in high-quality molecular imaging and pharmacokinetic study of radioactive compounds. With this sort of data, it is then possible to understand the natural history of infection in animal models as well as define the biodistribution and efficacy of small molecules and vaccines. Staff members that manage and support the Core facilities are working hard to provide access to these exceptional services by collaborating with companies and institutions across the globe. “There are a number of possible types of usage,” states Severson. “An investigator may collaborate with CPM or UofL faculty to submit grants and contracts or work with the RBL Shared Resources staff for regulatory support. Moreover, external investigators may directly access the facility and publish their findings independently with UofL regulatory oversight.” Despite these services having only been around for a short period, there is already significant evidence of knowledge sharing and collaboration taking place with internal and external partners. “The construction of RBL was the major reason for relocating my research programme from University of Maryland to UofL,” explains Dr Igor Lukashevich, who is a Professor of Pharmacology in the UofL School of Medicine. “The powerful live-imaging technology provided as a part of the Shared Resources is a unique feature of RBL.” Jonsson is proud of the collaboration opportunities and improved research quality to which the unique BSL-3 Shared Resources Service Center has given way. She states: “We want to bring visibility to our resources and outreach aims to foster regional and national partnerships as well as bring external fee-for-service research to the RBL. The Center is a benefit for all who use it”. EXPANDING THE LABORATORY In 2009, Jonsson petitioned the National Institutes of Health (NIH) to expand the RBL’s facilities, and for her efforts, she received US $9.8 million to do the job. This expansion, which will also be of a green design, will be completed in summer 2014. The extension will take the RBL’s state-of-theart biosafety facility to a whole new level. For example, the changes will facilitate translational studies in animal models, such as mice and ferrets, and it will permit preclinical evaluation and realtime data upload of vaccines and antivirals. At present this is impossible in the facility’s current configuration. Moreover, the changes to the RBL will shepherd in many value-adding benefits, such as hands-on animal BSL-2 clinical procedure training and enabling full diagnostics of vaccine, therapeutic and antiviral countermeasures by supporting clinical chemistry, haematology and pathology activities. FUNDING National Institutes of Health (NIH) Commercial Partners CONTACT Professor Colleen B Jonsson Director Clinical & Translational Research Building Sixth Floor, 505 South Hancock Louisville, Kentucky 40202 USA T +1 502 852 5773 E [email protected] Dr William E Severson Director, Shared Resources Service Center T +1 502 852 1546 E [email protected] http://centerforpredictivemedicine.org COLLEEN JONSSON joined the University of Louisville in 2008 as Director of The Center for Predictive Medicine for Biodefense and Emerging Diseases (CPM) and Professor of Microbiology. In addition to recruitment of faculty to the new Center, she led the completion of the construction, commissioning and in autumn 2010 celebrated the opening of the Regional Biocontainment Laboratory (RBL). WILLIAM SEVERSON joined the CPM IN 2011 to lead the management of the RBL. Since opening, Jonsson and Severson have worked with numerous academic, government and commercial institutions in the pursuit of new targets, small molecules and vaccines for deadly pathogens. WWW.RESEARCHMEDIA.EU 37