The candidate is a Burn Critical Care Surgeon with a clinical expertise in pediatric and adult Burn care. His previous background in basic sciences research and an established commitment to apply these skills to the study immune dysfunction in burn patients. The objective of this K08 proposal is to obtain the advanced mechanistic training required to achieve the candidate's long-term career goal of becoming an independently funded physician-scientist, leading a laboratory focused on developing novel therapeutics for inhalation injury and novel biomarker discovery. Specifically the candidate's short-term career goals of this proposal are: 1. Gain knowledge and skills that are currently outside his field of expertise that are relevant to establish a translational research project studying the role of innate immune activation by inhaled acute toxins;2. Improve his abilities in the analysis and design of both observational and interventional clinical research through formal coursework, establishing collaborations with researchers, and mentoring (formal and informal) from experienced investigators;3. Continue to collect data and further refine a hypothesis driven proposal for future, in depth studies with the goal of developing potential therapeutic strategies to mitigate these effects, along with presentations and publications that will allow him to apply for a R01 in 2017. The candidate's overall research goal is to understand the mechanism of increased susceptibility to bacterial infections in patients with inhalation injuries. The candidate hypothesizes, in Aim 1 the Innate immune cells in patients'lungs undergo differential polarization early (M2) and late (M1) after inhalation injury and / or cutaneous burn that can be reversed therapeutically.
In Aim 2 specific innate signaling profiles, increased concentrations of DAMPs and specific cytokine profiles over time will be predictive of poor clinical outcome after inhalation injury and / or cutaneous burn.
These aims support the candidate's career development by providing training in mechanistic aspects of lung biology, as well as the study of innate immune dysfunction. Additional key elements of the candidate's training plan include: 1) advanced coursework in computational biology and statistical modeling;2) a mentorship and advising team, which includes internationally-recognized, independently-funded investigators with expertise in host-microbial interactions, lung biology, and immunology;and 3) scholarly activities designed to foster independence and national recognition. Finally, the candidate's research environment is based in a pre- eminent academic research institution (the University of North Carolina at Chapel Hill) with access to NIH- funded centers (including the Center for Environmental Medicine Asthma and Lung Biology) that are tailored to support the proposed studies. This environment will provide a productive and collaborative atmosphere in which to accomplish the described research and training goals.
Inhalation injury is one of the most lethal injuries of burn victims that can increase the likelihood of mortality by up to 16 times in people with concomitant thermal injury;often secondary to complications associated with acute lung injury (ALI) and pneumonia. Little is known about the factors associated with susceptibility and severity of bacterial infection and respiratory complications. The goal of this proposal and of subsequent studies is to understand and investigate the cellular mechanisms underlying pulmonary immune suppression, ALI, and infection after inhalation +/- burn injury with the intent of developing therapeutics to decrease the morbidity and mortality associated with this injury.
|Dunn, Julia L M; Kartchner, Laurel B; Stepp, Wesley H et al. (2018) Blocking CXCL1-dependent neutrophil recruitment prevents immune damage and reduces pulmonary bacterial infection after inhalation injury. Am J Physiol Lung Cell Mol Physiol 314:L822-L834|
|Coleman Jr, Leon G; Maile, Robert; Jones, Samuel W et al. (2018) HMGB1/IL-1? complexes in plasma microvesicles modulate immune responses to burn injury. PLoS One 13:e0195335|
|Jones, Samuel W; Williams, Felicia N; Cairns, Bruce A et al. (2017) Inhalation Injury: Pathophysiology, Diagnosis, and Treatment. Clin Plast Surg 44:505-511|
|Lachiewicz, Anne M; Weber, David J; van Duin, David et al. (2017) From VAP to VAE: Implications of the New CDC Definitions on a Burn Intensive Care Unit Population. Infect Control Hosp Epidemiol 38:867-869|
|Lachiewicz, Anne M; Williams, Felicia N; Carson, Shannon S et al. (2017) Improving Research Enrollment of Severe Burn Patients. J Burn Care Res 38:e807-e813|
|Strassle, Paula D; Williams, Felicia N; Weber, David J et al. (2017) Risk Factors for Healthcare-Associated Infections in Adult Burn Patients. Infect Control Hosp Epidemiol 38:1441-1448|
|Eitas, Timothy K; Stepp, Wesley H; Sjeklocha, Lucas et al. (2017) Differential regulation of innate immune cytokine production through pharmacological activation of Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) in burn patient immune cells and monocytes. PLoS One 12:e0184164|
|Strassle, Paula D; Williams, Felicia N; Napravnik, Sonia et al. (2017) Improved Survival of Patients With Extensive Burns: Trends in Patient Characteristics and Mortality Among Burn Patients in a Tertiary Care Burn Facility, 2004-2013. J Burn Care Res 38:187-193|
|van Duin, David; Strassle, Paula D; DiBiase, Lauren M et al. (2016) Timeline of health care-associated infections and pathogens after burn injuries. Am J Infect Control 44:1511-1516|
|Lachiewicz, Anne M; van Duin, David; DiBiase, Lauren M et al. (2015) Rates of hospital-associated respiratory infections and associated pathogens in a regional burn center, 2008-2012. Infect Control Hosp Epidemiol 36:601-3|
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