Award Data

The advent of checkpoint inhibitor (CPI) therapy in human cancer has dramatically changed the landscape of treatment strategies in recent years. Previously, cancers with largely ineffective therapeutics and a poor prognosis, such as melanoma, have experienced significant advances of patients able to extend survival and/or progression free disease. Within the tumor microenvironment, a number of imm ...

Summary Technology for studying the higher order structure (HOS) and interactions of biomolecules is a highlighted NIGMS SBIR/STTR research topic. Mass-spectrometric methods for studying HOS include hydroxyl radical footprinting as well as chemical methods to covalently label amino acid side-chain functional groups, and also hydrogen/deuterium exchange (HDX) on protein backbone amides. These metho ...

Open-angle glaucoma is the second leading cause of blindness worldwide, affecting nearly 70 million individuals. Nonsynonymous mutations in the myocilin gene lead to the most common hereditary form of open-angle glaucoma and account for 3-4% of all cases. Disease-causing mutations, localized to its olfactomedin domain (mOLF), destabilize the myocilin protein, leading to its misfolding and accumula ...

Project Summary Genetic and pathologic evidence in andapos;pureandapos; tauopathies such as Progressive Supranuclear Palsy (PSP), Corticobasilar Degeneration (CBD) and some cases of Fronto-temporal Dementia (FTD) directly implicate tau as causing neuronal cell death, while in Alzheimer’s Disease (AD) tau accumulation correlates with development and progression of cognitive impairment. Because of ...

PROJECT SUMMARY/ABSTRACT Peripheral artery disease (PAD) affects nearly 12 million people in the United States. One of the most common surgical therapies is peripheral artery bypass grafting (PABG). Some patients are eligible for less invasive treatment options like angioplasty, but patients with calcified lesions are not. In patients that do receive PABG, approximately 20% fail within the first y ...

PROJECT SUMMARY There is an increased interest in peptide medicines in pharmaceutical research and development (Randamp;D) because peptides are recognized as highly selective and efficacious, and at the same time relatively safe and well tolerated. Chemo-enzymatic peptide synthesis (CEPS) using peptide ligases features excellent purity and yield, thus becoming an attractive method to replace tradi ...

Project Summary Natural products (NPs) and derivatives thereof provide a rich source of chemical matter for drug discovery and development. Over the past 30 years, NP-derived drugs have accounted for more than 35% of FDA approvals. Despite their demonstrated importance, development of new NPs has slowed over the past 15 years due to the lack of efficient methods for discovery, production, and opti ...

RA is one of the most common chronic autoimmune disorders that can lead to complete joint destruction and severe disability if untreated. There is no cure for RA and up to 50% of RA patients do not respond to anti-TNF therapies as circulating Th-17/IL-17 levels are highly elevated subsequent to TNF blockade. For this subset of RA patients, disruption of a novel pathway that impairs the synergy bet ...

PROJECT SUMMARY There is an urgent need for the development of approaches to prevent cardiotoxicity in cancer patients being treated with anthracyclines, an important class of drugs in the treatment of cancer (e.g. doxorubicin). Anthracycline treatment-related cardiotoxicity is a major clinical problem that severely impacts patient care and also limits dose and usage. More than a quarter of patien ...

PROJECT SUMMARY There is an urgent need for the development of new approaches to treat patients suffering from Ulcerative Colitis (UC), which is estimated to impact approximately one million adults in the United States, leading to morbidity, heightened risk of cancer, and mortality. In multiple preclinical studies, we and others have defined the therapeutic potential of low-dose exogenous carbon m ...