NIH

Cellular stress responses play essential roles in cell and organismal survival and contribute to a wide range of physiological processes and diseases in humans. The molecular architecture of most stress response pathways are well defined. A striking exception to this is osmotic stress response, where the relevant stress sensors and signaling mechanisms in animals are poorly understood. Most studies of the osmotic stress response use cultured cells, where in vivo complexities, i.e. the extracellular matrix, tissue mechanical properties, etc., are not replicated.

Cardiovascular disease (CVD) is a leading cause of mortality and morbidity and disproportionately affects Black American women. Compelling evidence highlights pregnancy as an important window for identifying future CVD risk. Although Black women are also at elevated risk for cardiovascular complications during pregnancy, heterogeneity is poorly understood and differentiated phenotypes of CVD risk before, during and after pregnancy are lacking.

Patients with advanced liver disease often experience fluid retention and electrolyte disturbances due in part to activation of the renin-angiotensin-aldosterone system. Aldosterone activates the epithelial Na+ channel (ENaC) in the distal nephron, enhancing urinary Na+ retention and K+ excretion. But many liver disease patients experience fluid retention without apparent activation of the renin-angiotensin-aldosterone system. Liver disease patients also frequently exhibit elevated plasma bile acids and hyperbilirubinemia.

Allergic asthma is a chronic inflammatory disease of the lung that drives a type 2 cytokine response (such as IL- 4, IL-5, and IL-13) predominately produced by activated CD4 T cells of a Th2 phenotype in response to exposure with environmental allergens. The master transcription factor GATA3 is known to drive Th2 development and promote type 2 cytokine production, however, the molecular pathways that drive Th2 cells to allergens at both the initiation and recall stages are not well understood.

Trauma triage predisposes to diagnostic errors because of the need for decision making under conditions of uncertainty and time-pressure. Diagnostic errors increase mortality, disability, pain, and loss of independence. Elderly patients are particularly vulnerable because they not only disproportionately experience these errors but also lack the resilience to tolerate sub-optimal care. The absence of interventions to improve the diagnostic process is a critical barrier to alleviating the burden that injury imposes on patients.

This resubmission is for a Mentored Patient-Oriented Research Career Development Award entitled “The Gut Microbiome in Carbapenem Resistant Enterobacteriaceae (CRE) Colonization, Persistence, Infection, and Tolerance after Lung or Liver Transplantation.” I am an Assistant Professor of Medicine and Transplant Infectious Diseases physician at the University of Pittsburgh Medical Center (UPMC). I require additional training to develop expertise as a translational researcher.

Our overarching goal is to develop minimally invasive approaches to better predict outcome and novel mechanisms in alcoholic hepatitis (AH). AH is characterized by acute hepatic decompensation and multiple organ failure. Although supportive care for AH has improved, short-term mortality has largely remained unchanged (30-40%) for decades. Effective approaches to predict risk hamper the treatment of AH. The hepatic extracellular matrix (ECM) responds dynamically to organ injury and ECM turnover increases; we propose to take advantage of this to develop new biomarkers for AH.

This K23 application will provide the applicant, a clinical psychologist with expertise in neuroimaging and computational modeling, with training and mentored research experience towards an independent research career studying disrupted learning processes in anxiety disorders. Training activities will focus on: 1) clinically informative applications of computational modeling and neuroimaging in anxiety, 2) advanced computational modeling of uncertainty and exploration, and 3) ecological momentary assessment of behavioral avoidance.

This application is for a research training grant focused on training the next generation of academic cardiac and thoracic surgeons. Given the current and future shortage of cardiothoracic surgeons, the extremely diverse clinical activities, and broad array of conditions treated by cardiac and thoracic surgeons, an NIH T32 training program in cardiothoracic surgery is an emergent unmet need to improve the cardiothoracic surgical workforce.

Do Changes in Diet Quality in a Weight Loss Trial Affect Cardiometabolic Risk? Jessica Cheng Project Summary/Abstract Although the importance of diet for weight loss, the prevention of chronic disease, and overall health has long been clear to researchers, weight loss intervention research favors calorie and fat reduction approaches but does not rigorously assess and report the impact of interventions on diet quality. The proposed research project will assess diet quality change based on 24-hour dietary recall data collected as part of the SMARTER randomized control trial (R01 HL131583).