NIH

There are seven known cancer viruses, two of which (Kaposi's sarcoma herpesvirus, KSHV/HHV8, and Merkel cell polyomavirus, MCV) were discovered by my laboratory. This R35 application will consolidate currently funded research in my laboratory and provide resources to complete currently unfunded research. It focuses on three main areas: 1) Merkel cell polyomavirus-related cancer and oncogenesis: MCV is the first polyomavirus known to cause human cancer.

This application is for a Mentored Patient-Oriented Research Career Development Award entitled “Microbiome-based diagnosis of pneumonia in the acute respiratory distress syndrome”. I am a Pulmonary and Critical Care Medicine Fellow at the University of Pittsburgh and I require additional training to develop expertise as a translational researcher in the microbiome of critical illness. The central objective of my research is to utilize emerging microbial DNA sequencing techniques for faster and more accurate diagnosis of pneumonia in critically-ill patients.

The perturbation in chromatin structure is one of the most striking and characteristic changes in cancer cells and remains one of the hallmarks in cancer diagnosis. At the molecular level, it is well recognized that aberrant epigenetic marks of DNA methylation and histone modification as well as chromatin organization play an important role in cancer progression, both globally and locally.

The confluence of obesity and pre-diabetes in older adults substantially increases the risk of diabetes, and accelerates functional decline, multimorbidity, disability, and death. More research is needed to refine and extend preventive interventions to reduce burden for elders and society. For over a decade efficacious 6- and 12-month Diabetes Prevention Program (DPP) lifestyle interventions have been translated successfully and demonstrated positive impact.

The clinical care of neglected diseases such as pulmonary hypertension (PH) has not yet benefited from large scale –omics data analysis. Evidence suggests parallels in the pathogenesis of cancer, where –omics data are available, and PH, thus making a repurposing of chemotherapeutics for PH possible. This proposal leverages a network-based analysis of cancer –omics data to predict in silico and define experimentally which chemotherapies may offer the most robust actions in PH.

Slip and fall accidents are a major and growing source of occupational injuries. Slip-resistant shoes with a high coefficient of friction (COF) are effective at a reducing slipping risk. However, neither experts nor industry has agreed upon a consistent set of criteria for labeling a shoe as slip-resistant. A consequence of this lack of standardization is that significant variability exists across shoes that are labeled slip-resistant. Furthermore, independent testing of shoe COF is expensive, which may limit its use by employers and employees.

Disruptions in dopamine (DA) signaling are central to symptom presentation of several devastating neuropsychological disorders, such as schizophrenia, depression, Parkinson’s, and addiction, making normalization of DA signaling a primary concern in mental health(1-3). However, with the troubling side effects that can occur with direct dopaminergic manipulation(4; 3), and the identification of pathology within the circuits controlling DA neurons(6), the focus of much research has turned to the afferent regulation of the DA system.

Midcareer Investigator Award in Translational Patient-Oriented Research in Aging This application is for a K24 Midcareer Investigator Award in Patient-Oriented Research to promote mentoring and career development in dissemination and implementation research that improves mobility and prevents disability in community-dwelling older adults. Dr. Jennifer Brach, PI of the proposed award, is a physical therapist, epidemiologist and scientist committed to mentoring health professional trainees and junior faculty and working to improve the mobility and quality of life of older adults.

Influenza A virus (IAV) causes a significant global burden and the emergence of novel pandemic viruses is a constant threat heightened by increasing incidence of highly pathogenic avian IAV in migratory birds and poultry and cases of human transmission (e.g. H5N1, H7N9). Since seasonal vaccines are ineffective against emerging pandemic IAV strains and resistance to current licensed antivirals is easily acquired, the development of additional therapeutic strategies is required.

Nearly 800,000 patients require invasive mechanical ventilation for acute respiratory failure in the United States each year. Among those who recover to the point of extubation, a substantial proportion remain at high risk for extubation failure, i.e., recurrent respiratory failure requiring reintubation within 48 hours of extubation. For these vulnerable patients, extubation directly to noninvasive ventilation reduces the risk of recurrent respiratory failure, reintubation, and death.