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Project Summary The proposed project will develop a breakthrough endovascular sensor technology to allow for real-time quantification of the mitral coaptation force (MCF) of the mitral valve during both open and percutaneous mitral valve repair (MVR). Mitral regurgitation (MR) is the most common heart valve disorder in the U.S. population, with over 2 million individuals affected. Current methods ...

PROJECT SUMMARY Data is a critical and highly valuable commodity, driving meaningful change in our society, especially when it pertains to patient care and biomedical research. Currently, institutions pay inordinate sums to increase, regain, and complement their data panels. As an extra burden, data legislation and privacy protection regulations introduce barriers to forming effective partnerships ...

ABSTRACT SaCas9 is a major gene editing nuclease that is preferred for in vivo applications thanks to its relatively smaller size compared to that of spCas9. One limiting factor for the use of saCas9 is its strict PAM requirement of NNGRRT. In addition, there are limited efforts to reduce saCas9’s off-target editing rates. In Aim 1, we propose a computational approach to relax saCas9’s PAM req ...

Tarn Biosciences, Inc. is a start-up pharmaceutical company headquartered in East Lansing, Michigan. The company is developing new therapies for tuberculosis (TB). The goal of this STTR is to develop the MmpL3 inhibitor, HC2099, as a new treatment for drug susceptible and multidrug-resistant TB (MDR-TB). In 2019, 10 million people worldwide fell ill to TB with ~ 1.4 million lives lost. Standard-of ...

PROJECT SUMMARY/ABSTRACTUsher syndrome type 3A (USH3A), an autosomal recessive disorder, is characterized by progressive loss of hearing and vision due to a clarin-1 (CLRN1) gene mutation. A person with type 3 Usher syndrome will usually require cochlea implants by mid- to late adulthood and classified as being legally blind. The management of the chronic, progressive, severe vision loss (retiniti ...

ABSTRACT The goal of this study is to develop an RNAi-based genetic precision medicine to treat alcohol associated liver disease (AALD). AALD is a devastating health problem worldwide, accounts for the majority of alcohol-related mortality globally and is the second most indication for liver transplantation in the US. The current medical management for AALD remains limited, and no proven pathobiol ...

PROJECT SUMMARY We propose to develop a novel non-contact, label-free multimodality imager that provides real-time intraoperative identification of nerves within the surgical field-of-view to facilitate the prevention of unintended nerve damage (termed iatrogenic nerve injury) during surgical procedures, as they are a major source of postsurgical complications, e.g., chronic pain. In the United St ...

Abstract There is an unmet need to develop treatments for senile osteoporosis, a disorder characterized by an age-related reciprocal decrease in osteogenesis and increase in bone marrow fat. Senile osteoporosis resembles disuse osteopenia, suggesting its pathogenesis involves impaired bone mechanosensing. We discovered that the polycystin heterotrimeric complex (1PC1+3PC2) functions as a mechanose ...

Project SummaryEpilepsy is one of the most common brain disorders. Current drugs have limited efficacy. Identifying new targeted drugs that can be used as safer, more effective therapies is in urgent unmet need. Selective inhibition of the transient receptor potential canonical 3 (TRPC3) emerges as a novel strategy to impede epilepsy. However, the currently best selective TRPC3 inhibitor, Pyr3, ha ...

Project Summary Volume overload (congestion) occurs in patients with heart failure (HF) and is the leading cause of hospitalization in the elderly worldwide. Unfortunately, clinical signs and symptoms; laboratory values; and existing diagnostic tools are unreliable in providing accurate assessment of volume status. Using a unique physiologic signal, Non-Invasive Venous waveform Analysis (NIVA), Vo ...