NIH

Intensive care provides lifesaving monitoring and intervention. However, extensive literature reports that intensive care unit (ICU) survivors, particularly older patients, too often experience significant deficits following discharge that impair quality of life for at least 1 year after discharge. Delirium, which presents in 30-80% of ICU patients depending upon specific population, has been associated with worse outcomes, including cognitive dysfunction and progression to dementia, and therefore has been a focus of intervention studies to improve ICU survivor outcomes.

Gangliosides are complex sialic acid-containing glycosphingolipids that are particularly enriched in the brain and are critical for brain development and function. GM3 synthase deficiency is a genetic disorder of ganglioside biosynthesis occurring primarily, but not exclusively, in the Old Order Amish. GM3, which the patients cannot synthesize, is itself not abundant in the brain; rather, it serves as the common precursor for all downstream gangliosides. Thus, patients completely lack cell-surface gangliosides.

Project Summary/Abstract Colorectal cancer (CRC) is a leading cause of cancer-related death and its incidence is on the rise, particularly in young people. Therapy for late stage CRC is often ineffective and colorectal tumors are most often detected at stage 3 or 4. Immunotherapy is revolutionizing the treatment of many types of cancer but is only effective for a very small subset of CRC patients. Thus, there is a tremendous need for improved therapies for CRC.

PROJECT SUMMARY Epstein-Barr virus (EBV) was the first human cancer-causing virus to be discovered. EBV primarily infects lymphocytes and epithelial cells, which can result in a wide range of lymphomas and carcinomas, respectively. Over 90% of the world’s population is infected with this virus, but infection is mostly asymptomatic in healthy individuals. The cancer-causing potential of EBV becomes evident particularly in immunocompromised individuals, e.g.

Cancers arise through the accumulation of genetic and epigenetic alterations that often target signal transduction pathways, leading to dysregulation of downstream transcriptional effectors and widespread gene expression changes. Since many targeted therapies are small molecule inhibitors of signal transduction proteins or monoclonal antibodies against growth factor receptors, deciphering the signaling pathways that are deregulated in a given tumor in order to personalize therapy is a major goal of cancer genomics.

The genome of herpes simplex virus encodes mRNAs for about 90 protein coding genes in addition to numerous noncoding RNAs. Sets of these genes are transcribed in a sequential manner by RNA pol II. The timing of their expression is dependent on the cis-acting sites for cellular transcription factors in their promoters, their requirements for virus transcription factors, and the state of viral DNA replication.

Bronchopulmonary dysplasia (BPD) remains a significant complication of prematurity with an incidence of 7% in all preterm infants and nearly 70% in infants born ≤28 weeks. Current clinical strategies to mitigate the development and progression of BPD include mechanical ventilation and pharmacologic therapy including surfactants and long-acting synthetic glucocorticoids (sGCs) such as dexamethasone (Dex).

PROJECT SUMMARY / ABSTRACT: The overarching goal of this Pathway to Independence Award is to facilitate the development of César G. Escobar-Viera, PhD, MD, MPH, into an independent researcher, with expertise in advanced quantitative and qualitative methods to determine the role of social media on depression among lesbian, gay, and bisexual U.S. young adults (LGBYA). Ultimately, the PI seeks to leverage evidence-based SM interventions to ameliorate depression among LGBYA, which will ultimately help to reduce mental health disparities for this group.

PROJECT SUMMARY: Oral cancer pain results from activation of primary afferent neurons by cancer-secreted mediators. My previous work demonstrated that mice bearing tongue cancers induced by 4-nitroquinoline-1-oxide (4NQO)- carcinogenesis exhibit nociceptive behavior and trigeminal ganglia neurons (TGNs) innervating the tongue become hyperexcitable. Oral cancer cells also secrete neurotrophic factors that induce neuronal sprouting into the cancer, while local neurotransmitter release from TGNs innervating the cancer has been linked to carcinogenesis.

Project Summary: The purpose of this five-year proposal is to provide an integrative and personalized training program for the applicant to transition into an independent academic position as a basic scientist in cardiac development and regeneration. The long-term goal is to understand the underlying mechanisms of atrial CM lineage development and atria-related congenital heart diseases.