NIH

Alcohol-related liver disease (ALD) is a prevalent clinical problem, with many knowledge gaps in the pathogenesis of ALD, including the role and regulation of inflammatory and tissue reactions. Our overarching goal is to identify key new players in alcohol-mediated effects on development and progression of liver damage and fibrosis that could translate to targeted therapies. The extracellular matrix (ECM) and ECM dyshomeostasis are known to be important in ALD.

The Department of Bioengineering, University of Pittsburgh (UPitt) is seeking continued support for a predoctoral training program (8 positions/year) aimed at educating talented students from engineering and other quantitative sciences for careers in biomedical research in the cardiovascular area. UPitt has been at the forefront of education and research in this field, with two key components contributing to this status.

This proposal requests support for the five-year continuation of our NIMH-funded institutional training grant, “Clinical and Translational Research Training in Late-Life Mood Disorders” (T32 MH019986), Years 26-30. The primary goal of this two-year post-doctoral fellowship (three years in selected case) is to provide rigorous training in the basic foundations and methodologic tools necessary for successful clinical and translational investigation in geriatric mental health and psychiatry.

ABSTRACT: Frequency-following responses (FFRs) are scalp-recorded electrophysiological ‘neurophonic’ potentials that reflect phase-locked activity from neural ensembles across the auditory pathway. FFRs provide a neural snapshot of the integrity of supra-threshold speech processing that can be measured non-invasively using a minimal electrophysiological set-up that already exists in audiology clinics, has high test-retest reliability, and requires minimal subject preparation.

ABSTRACT In recent decades multiple high-profile clinical trials have provided a rigorous evidence base for the care of patients with acute respiratory failure requiring mechanical ventilation. Yet many patients still do not receive these evidence-based treatments proven to save lives. The overarching goal of our research program is to address this issue by defining the relationship between ICU organizational behavior and evidence-uptake in critical care.

Overall Summary/Abstract Our research focuses on understanding the pathophysiological mechanisms that lead individuals to develop dementia, especially Alzheimer’s disease (AD). Our findings, as well as those from others, indicate that there is a complex interaction of clinical and subclinical cerebral and systemic factors during the pre-clinical phases of AD, some which convey vulnerability and some which convey resilience.

Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. Recent improvements in lung cancer treatment have come from the identification of distinct patient subgroups with targetable molecular drivers. The current paradigm is typified by the treatment of EGFR mutant non-small cell lung cancer (NSCLC) with the targeted tyrosine kinase inhibitor (TKI), erlotinib. An emerging subgroup are those 8-14% of NSCLC patients with targetable alterations in the hepatocyte growth factor (HGF)/c-Met (MET) pathway.

Pulmonary arterial hypertension (PAH) is an enigmatic vascular disease characterized by pulmonary vascular remodeling, an increased pulmonary vascular resistance, and subsequent right ventricular hypertrophy and failure. There is an increased predisposition to PAH in HIV-infected populations, and as a historically neglected vascular disease, the pathogenesis of HIV-induced PAH (HIV-PAH) remains largely unknown.

DESCRIPTION (provided by applicant): Differences in our individual genomes give rise to most of human diversity. This uniqueness of every human being underpins the purpose of precision medicine, which posits that disease prediction, diagnosis, and treatment for each individual is based on personal genomic variations. The rapid advancement of genome editing technology has led to numerous promising preclinical studies in muscular dystrophies (MDs).