Addressing infectious disease in a therapeutically relevant fashion requires an understanding of both the microbial virulence factors that contribute to the disease process and how these factors impact the host immunological and inflammatory response to define the clinical outcome. Achieving this understanding provides a perfect opportunity for clinically relevant translational research and is the overriding theme of our proposed Center for Microbial Pathogenesis and Host Inflammatory Responses. The key element in the development of our Center is to bring together promising young investigators, each under the mentorship of established senior faculty, whose research is consistent with this scientific theme. The underlying hypothesis that ties these investigators together is that targeting diverse pathogens and pathogenic processes in an integrated, highly structured environment will optimize opportunities for the elucidation of common themes with respect to the host response and its adverse consequences on the disease process. To this end, this application brings together as Project Leaders junior investigators who focus on viral (Forrest), bacterial (Scurlock), and parasitic (Stumhofer) pathogens. Additionally, based on studies suggesting that persistent viral and bacterial infection plays a key role in the development of many chronic diseases, a fourth investigator (Ortmann) will focus on the host response in inflammatory arthritis, the principal example of which is rheumatoid arthritis. We propose to (Aim 1) enact an integrated and interactive faculty development plan for young investigators in the context of the underlying scientific theme with the immediate goal of leveraging the resources of the Center to enable these investigators to establish independent research careers and taking specific steps to ensure the absence of administrative or technical barriers to their success;
(Aim 2) strengthen the biomedical research infrastructure on the host campuses of the University of Arkansas for Medical Sciences and Arkansas Children's Hospital;
and (Aim 3) build on the success of these first two aims to recruit additional junior faculty and create the collaborative and synergistic environment required to establish a self-sustaining Center of Biomedical Research Excellence. As a means of further optimizing the academic, experimental, and translational synergy, specific consideration is also given to integration with existing NCRRfunded programs on the host campuses. These include the Arkansas INBRE, the UAMS CTSA Center for Clinical and Translational Research, and the Center for Translational Neuroscience, an established COBRE. Bringing all of these elements together will provide an integrated and supportive research infrastructure that will significantly enhance the ability of th Project Leaders to establish independent, extramurally funded research programs. The long-term goal is to integrate the Project Leaders included in this application with newly recruited junior investigators and with established investigators who can significantly expand their existing research programs in a manner consistent with the underlying scientific theme, to create the collaborative and translational synergy required for the development of successful program project applications and a self-sustaining translational research center that can impact human health.

Public Health Relevance

Infectious disease remains a persistent problem that impacts all medical specialties. This is particularly true in an era of increased resistance to antimicrobial agents. In this context, it is important to consider not just the pathogen, but also its impact on the body's immunological and inflammatory response, which often plays a key role in defining the clinical outcome. Thus, investigating the complex interactions between microbial pathogens and their human hosts from the perspectives of both the pathogen itself and the host response has the potential to significantly enhance the ability to control the devastating consequences of many infectious diseases, including those caused by pathogens that are resistant to antibiotics.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM103625-02
Application #
8523923
Study Section
Special Emphasis Panel (ZRR1-RI-B (01))
Program Officer
Douthard, Regine
Project Start
2012-08-15
Project End
2017-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
2
Fiscal Year
2013
Total Cost
$1,941,709
Indirect Cost
$563,882
Name
University of Arkansas for Medical Sciences
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
122452563
City
Little Rock
State
AR
Country
United States
Zip Code
72205
Kennedy, J L; Denson, J L; Schwalm, K S et al. (2017) Complete Genome Sequence of a Novel WU Polyomavirus Isolate from Arkansas, USA, Associated with Acute Respiratory Infection. Genome Announc 5:
Lei, Mei G; Gupta, Ravi Kr; Lee, Chia Y (2017) Proteomics of Staphylococcus aureus biofilm matrix in a rat model of orthopedic implant-associated infection. PLoS One 12:e0187981
Koonce, Nathan A; Griffin, Robert J; Dings, Ruud P M (2017) Galectin-1 Inhibitor OTX008 Induces Tumor Vessel Normalization and Tumor Growth Inhibition in Human Head and Neck Squamous Cell Carcinoma Models. Int J Mol Sci 18:
Kieber-Emmons, Thomas; Monzavi-Karbassi, Behjatolah; Hutchins, Laura F et al. (2017) Harnessing benefit from targeting tumor associated carbohydrate antigens. Hum Vaccin Immunother 13:323-331
Kaldhone, Pravin R; Khajanchi, Bijay K; Han, Jing et al. (2017) Draft Genome Sequences of Salmonella enterica Isolates Containing Incompatibility Group I1 Plasmids from Swine, Poultry, and Human Sources. Genome Announc 5:
Hartman, Jessica H; Miller, Grover P; Caro, Andres A et al. (2017) 1,3-Butadiene-induced mitochondrial dysfunction is correlated with mitochondrial CYP2E1 activity in Collaborative Cross mice. Toxicology 378:114-124
Khajanchi, Bijay K; Hasan, Nur A; Choi, Seon Young et al. (2017) Comparative genomic analysis and characterization of incompatibility group FIB plasmid encoded virulence factors of Salmonella enterica isolated from food sources. BMC Genomics 18:570
Simon, Emily J; Howells, Morgan A; Stuart, Johnasha D et al. (2017) Serotype-Specific Killing of Large Cell Carcinoma Cells by Reovirus. Viruses 9:
Holthoff, Emily R; Byrum, Stephanie D; Mackintosh, Samuel G et al. (2017) Vulvar squamous cell carcinoma aggressiveness is associated with differential expression of collagen and STAT1. Clin Proteomics 14:40
Nounamo, Bernice; Li, Yibo; O'Byrne, Peter et al. (2017) An interaction domain in human SAMD9 is essential for myxoma virus host-range determinant M062 antagonism of host anti-viral function. Virology 503:94-102

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