Award Data

PROJECT SUMMARY Congenital Myasthenic Syndromes (CMS) are a group of clinically similar neuromuscular transmission disorders that differ in their underlying genetic mutation. While some phenotypical variation exists, CMS are commonly characterized by muscle weakness (myasthenia) that worsens with physical exertion. Defects in Collagen Q (ColQ), a multidomain functional protein of the Neuro Muscula ...

Project Summary Choroidal neovascularization (CNV) occurs in both age-related macular degeneration (AMD) and diabetic retinopathy (DR). While anti-VEGF treatment has improved the visual outcome considerably, they are far from achieving a 100% success rate (non-responsiveness between 8 and 50%). Inherited retinal degenerations (IRDs) are a group of heterogeneous, progressive, visually debilitating ...

Abstract Currently, clinically used drug abuse medications exist for treatment of addiction to opiates, alcohol, and nicotine, but not psychostimulants, such as methamphetamine (METH). Compounds that co-activate both nociceptin opioid peptide (NOP) and mu receptors have potential for treatment of drug abuse. In particular, buprenorphine, a partial mu agonist/kappa antagonist, which also acts as a ...

Background: Large scale studies have demonstrated that when patients struggle with life challenges that complicate their care (e.g., a lack of social support, competing responsibilities, or financial hardships), health care providers can improve health care outcomes and lower costs if they attempt to identify these “contextual factors” and address them in their care plan – a process termed � ...

For more than a decade, our work has focused on development of therapeutic interventions for viral- and bacterial-induced acute lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS). Significantly, we identified the Toll-like receptor 4 (TLR4) signaling pathway as key to the host response to influenza and secondary bacterial infection following influenza. We also identif ...

ABSTRACT Developing drugs that target the central nervous system (CNS) is hampered by an inability to perform direct in vivo preclinical measurements. Here, we propose to identify an optimal smoking cessation drug candidate by monitoring how our newly synthesized prodrugs alter real-time brain dopamine responses to nicotine. Varenicline (CHANTIX®) is the leading FDA-approved oral medication for s ...

Cardiotoxicity is a leading cause of drug discovery attrition across all of preclinical and clinical drug discovery. While the FDA and the Comprehensive in vitro Proarrhythmia Assay initiative (CiPA) are focused primarily on predicting proarrhythmic effects, drug attrition due to cardiomyopathy, or primary cardiac cytotoxicity, may be even more prevalent, is typically currently only carried out vi ...

ABSTRACT This Phase STTR Phase II proposal aims to engineer and scale-up a synthetic metabolic pathway in a microbial host to produce UDCA and related compounds. Additionally, the UDCA produced from the engineered synthetic metabolic pathway will be used to synthesize derivatives for testing in our Alzheimer’s Disease cell and animal models. The proposed work has high intellectual merit for the ...

ABSTRACT Despite treatment advances, the prognosis of adult patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and R/R diffuse large B-cell lymphoma (DLBCL) remains poor. Autologous T- cells modified to express a CD19-targeted chimeric antigen receptor (CAR T-cells) produce durable responses in subgroups of these patients, which has led to FDA approval of two su ...

Knee  Osteoarthritis  (KOA)  is  a  degenerative  joint  disease  that  leads  to  significant  pain  and  functional  disability  affecting  over  30%  of  older  adults  making  it  one  of  the  most  common  and  debilitating  conditions  related  to  aging.  This  disease  results  in  a  loss  of  mobility,  reduced  quality  of  life,  and  in ...