Colleen Jonsson, Ph.D.

Colleen Jonsson, Ph.D.

Dr. Jonsson joined UofL in August of 2008 as a Professor of Microbiology and Director of the Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases (CPM). Dr. Jonsson’s basic and translational research program spans over 20 years in the study of highly pathogenic, RNA viruses including investigations of hantaviruses, influenza viruses, SARS CoV and retroviruses. Her research has addressed basic questions of the viral life cycle, and the ecology and evolution of virus-host relationships.

UofL Regional Biocontainment Laboratory (RBL)

Her first efforts at UofL focused on launching the Regional Biocontainment Laboratory (RBL) located on Shelby Campus and recruitment of faculty and staff for the CPM (also see www.centerforpredictivemedicine.org). The RBL stands as a critical regional resource for those engaged in research that requires biosafety level 3 (BSL-3) containment. Shortly after "911", the NIH implemented a competitive program for requests for Universities to build RBLs to address the critical need for secure BSL-3 resources for basic and translational research. The University of Louisville is one of 11 sites chosen to lead an RBL. The CPM and RBL provide an advanced state-of-the-art infrastructure to explore in vitro and in vivo models of infectious disease that require BSL-3 containment; the UofL RBL is certified for select agent use.

Hantaviruses

Hantavirus, family Bunyaviridae, have a trisegmented, negative-sense RNA genome. Hantaviruses were thought to cause hemorrhagic fever with renal syndrome disease only in Asia and Europe until 1993. In 1993, an outbreak of hantavirus pulmonary syndrome in the southwestern part of the USA led to the discovery of the first of many New World hantaviruses.  Hantaviruses are harbored by rodents, and hence, the epidemiology and evolution of these viruses and their diseases in humans reflects the geographical restriction imposed by the host range of its' specific rodent reservoir. Despite their global prevalence, outbreaks of illness are sporadic and unpredictable.  Much remains to be understood about the basic components of the life cycle and importantly, how the virus-host interplay leads to illness.

Translational Research for Viral Infections

Approximately 3.9 million people die from respiratory infectious diseases caused by viruses (World Health Report, 2008). Of these, acute respiratory infections such as those caused by respiratory syncytial viruses (RSV) are predicted to continue as the largest contributor to death due to infectious disease. Because many of these illnesses initially manifest as influenza-like symptoms, effective medical intervention requires rapid diagnosis and treatment during the earliest stages of infection. This is particularly critical in containment of outbreaks, as apparent during the SARS epidemic and H1N1 2009 pandemic. The challenges of rapid pathogen identification and treatment call for new approaches and tools that will allow clinicians to effectively diagnose an infection to administer early life-saving care to the patient.  Further, there is a critical need for new, broad spectrum antivirals for treatment of these emerging and reemerging viral diseases.

Molecular Imaging Approaches in the Study of infection.The Jonsson laboratory has been working on the development of models of the natural history of infection using PET/CT imaging with the goal of enabling studies in the mechanisms of immune response and pathogenesis in influenza A virus infection. Collaborators on this multidisciplinary effort include Dr. Daniel Mollula, NIH, and Drs. Haixun Guo and Chin Ng at UofL. Research efforts have recently focused on proof of concept studies focused on the progression of influenza A virus infection and inflammation of ferret using CT/PET imaging.

Drug Discovery for Emerging Viruses. Dr. Jonsson's basic research efforts have led to development of high-throughput screening approaches for several viruses to enable the discovery of small molecule inhibitors which have resulted in several patents for these early stage discovery efforts. Remarkably, the majority of human viruses have no treatment, vaccine or antiviral. At present, there are only sixty-two drugs approved by the FDA for the treatment of six different viral illnesses caused by hepatitis B and C, herpes, HIV, influenza, and RSV. Of these, 45% are for the treatment of HIV/AIDS. Combined, these statistics underscore the critical gap that remains to provide treatment for emerging viral diseases. The discovery of treatments for newly emerging and reemerging viruses requires intensive basic research efforts that identifies and validates targets for therapy as well as research that translates the target into in vitro assays to discover new drugs.  In general, this requires understanding the basic components discussed above as well as creating assays to probe for new drugs, and finally, having robust animal models that mimic the diseases in humans that one can use to screen for effective therapies.

Past and current multidisciplinary collaborative research efforts bring together teams to enable synthetic chemistry (Drs. Jennifer Golden, University of Kansas  and Jeffrey Arterburn, New Mexico State University), virology and animal model expertise (William Severson and Hoon Chung, UofL Connie Schmaljohn, USAMRIID) and high-throughput screening technologies in a concerted effort to identify small molecule inhibitors for hantaviruses, RSV, influenza A viruses, West Nile Virus and Venezuelen Equine Encephalitis Virus (VEEV).

Selected Publications

Jonsson, C.B., Figuerido, L., Vapalahti (2010) A Global Perspective on Hantavirus Ecology, Epidemiology and Disease. Clinical Micro. Rev. 23:412-441. PMID: 20375360

Wu, A. Zheng, H., Kraenzle, J., Biller A., Vanover, C.D., Proctor, M., Sherwood, L., Steffen, M., Chin Ng, C., Mollura, D.J., and Jonsson, C.B. (2012) Ferret Thoracic Anatomy by 18F-FDG PET/CT Imaging, Institute of Laboratory Animal Research Journal. 52:4 online.

Camp, J.V., Svensson, L.T., McBrayer,A.,  Jonsson, C.B.,  Liljeström, P., and Bruder, C.E.(2012) De-novo transcriptome sequencing of a normalized cDNA pool from influenza infected ferret tissues Host Gene. PLoS ONE 7: e37104.

Ljungberg K., McBrayer A., Camp J.V., Chu Y. K., Tapp R., Noah, D.L., Grimes, S., Proctor, M.L., Liljeström, P. Jonsson, C.B., Bruder, C.E. (2012) Host Gene Expression Signatures Discriminate between Ferrets Infected with Genetically Similar H1N1 Strains. PLoS ONE 7: e40743.

Jonsson, C.B,  Camp, J.V., Wu, A., Zheng, H., Kraenzle, J., Biller A., Vanover, C.D., Chu, Y-K, Ng, C., Proctor, M., Sherwood, L., Steffen, M., Mollura, D.J. (2012) Molecular Imaging Reveals a Progressive Pulmonary Inflammation in Lower Airways in Ferrets Infected with 2009 H1N1 Pandemic Influenza Virus PLoS ONE. 7: e40094

Cameron,MJ, Kelvin,AA, Leon,AJ, Cameron, CM,  Ran,R, Xu,L, Chu,Y, Danesh, A, Fang, Y, Li, Q, Anderson, A, Couch, R, Paquette, SG, Fomukong, NG, Kistner, O, Lauchart, M, Rowe, T, Harrod, KS, Jonsson, CB and Kelvin, DJ. (2012) Lack of innate interferon responses during SARS coronavirus infection in a vaccination and reinfection ferret model. PLoS ONE. 7: e45842

Moore, B.P., Chung, D.H., Matharu, D.S., Golden, J.E., Maddox, C., Rasmussen, L., Noah, J.W., Sosa, M.I., Ananthan, S., Tower, N.A., White, E.L., Jia, F., Prisinzano, T.E., Aubé, J., Jonsson, C.B., Severson, W.E. (2012) (S)-N-(2,5-Dimethylphenyl)-1-(quinoline-8-ylsulfonyl)pyrrolidine-2-carboxamide as a Small Molecule Inhibitor Probe for the Study of Respiratory Syncytial Virus Infection. J. Med. Chem.55(20): 8582–8587. PMID: 23043370

Chung, D., Moore, B.P., Matharu, D.S., Golden, J.E., Maddox, C., Rasmussen, L, Sosa, M.I., White, E.L., Ananthan, S., Jia, F., Jonsson, C.B., and W.E. Severson (2013). A cell based high-throughput screening approach for the discovery of new inhibitors of respiratory syncytial virus. Virology Journal 10:19.

Camp, J.V., Chu, Y-K, Chung, D., McAllister, R., Gerlach, R.L., Adcock, R.S., Wiemken, T.L., Peyrani, P., Ramirez, J., Summersgill, J.T., Jonsson, C.B. (2013) Phenotypic Differences in Virulence and Immune Response in Closely Related Clinical Isolates of Influenza A 2009 H1N1 Pandemic Viruses in Mice. PLoS ONE. 8(2): e56602.

Adedeji, A., Severson, W. Jonsson, C., Singh, K., Weiss, S., and Sarafianos, S. (2013) Novel Inhibitors of SARS-CoV Entry acting by Three Distinct Mechanisms. J. Virol. 87:8017-28

Bagci U, Foster B, Miller-Jaster K, Luna B, Dey B, Bishai WR, Jonsson CB, Jain S, Mollura DJ (2013) A computational pipeline for quantification of pulmonary infections in small animal models using serial PET-CT imaging. EJNMMI Res. 2013 3:55

Jonsson, C.B. Cole, K.S., Perlin,D.S., Roy, C.J.,and RBL Director Network. (2013) Challenges and Practices in Building and Implementing Biosafety and Biosecurity Programs to Enable Basic and Translational Research with Select Agents. J Bioterr Biodef S3:015. doi: 10.4172/2157-2526.

Chung, D.H.C., Västermark, A., Camp, J.V., McAllister, R.C., Remold, S., Bruder, C., Chu, Y., and Jonsson, C.B. (2013) The Murine Model for Hantaan Virus-Induced Lethal Disease Shows Two Distinct Paths in Viral Evolutionary Trajectory with or without Ribavirin Treatment. J. Virol. In press.