SUMMARY Fine tuning enzyme specificity is desired for industrial catalysis. Enzymes lacking structural characterization or favorable recombinant expression are not amenable to traditional directed evolution or de novo design approaches. “Monobodies” are synthetic binding proteins based off a human FN3 scaffold. When Monobodies bind allosterically near the enzyme active site,… Read More
SUMMARY After surgical removal of breast cancer tumors, adjuvant chemotherapy and radiation therapy have an absolute survival benefit of just 5-10%. Currently approved breast cancer diagnostics do not predict patient responses to these treatment options, despite the capability of such a diagnostic to avoid unnecessarily exposing patients to toxic side… Read More
SUMMARY Staphylococcus aureus infects 50,000 patients and kills 20,000 annually in the United States alone. With widespread antibiotic resistance, there is an urgent need for alternative mechanisms of targeting S. aureus infection. One way the pathogen mediates its virulence is by secreting the pore-forming cytotoxin α-hemolysin, which causes skin and… Read More
SUMMARY Adjuvant radiation therapy post-surgery remains largely ineffective, with just 5% of patients showing a survival benefit. Small molecule JAK inhibitors have shown efficacy in the clinic at treating these patients, yet problematically this approach is plagued by off-target toxicities and eventual development of treatment resistance. The inventors used an… Read More
SUMMARY Current immunotherapy approaches often focus on targeting a single immune checkpoint or suppressive pathway, which can be insufficient given the redundancy and adaptability of tumor-mediated immune evasion. Tumors can compensate for the blockade of one pathway by upregulating alternative suppressive mechanisms, leading to limited efficacy and the persistence of… Read More
SUMMARY kV radiation dose for imaging tumors is useful for direct monitoring and real-time organ tracking without relying on high-risk surgical implants. However, the utility of this approach is limited by concerns of radiation overdose associated with exposing patients to an additional radiation source other than the MV treatment dose. Read More
SUMMARY N-Acetylcysteine (NAC) is commonly used to break down mucous and lessen lung function decline but has traditionally shown low efficacy in treating patients with idiopathic pulmonary fibrosis (IPF). The only two FDA approved drugs to treat IPF have severe side effects, meaning there is an urgent need to find… Read More
SUMMARY An understanding of protein-protein interactions (PPIs) is critical to uncovering new disease pathophysiology and for developing small molecule and antibody treatments. Problematically, current approaches to assay PPIs are limited by sensitivity, signal to noise ratio, and the need to carefully optimize the assay for each new application. The inventors… Read More
SUMMARY Protein palmitoylation is a post translational modification of cystine protein residues, the dysregulation of which is implicated in diseases such as Alzheimer’s, cancers, and Huntington’s. Despite the importance of palmitoylation, the regulation of the enzymes that control it is poorly understood. The inventors designed an enzyme substrate analogue probe… Read More
SUMMARY ER-negative (ER-) breast cancers make up 20% of all breast cancer diagnosis. However, no gene signature exists for predicting drug sensitivity and prognosis. Therefore, the clinical standard remains treating patients with generic chemotherapy despite possible drug resistance. Glucocorticoid receptor (GR) regulates many genes that contribute to tumor viability, aggressiveness,… Read More
SUMMARY Electric stimulation of organs with implantable devices has demonstrated clinical utility for the treatment of a variety of diseases such as cardiac arrythmia. However, use of these technologies remains high risk, requiring either surgical implantation or permanent gene editing. The inventors synthesized silicon nanowires that are doped with gold… Read More
SUMMARY The development of cancer immunotherapies is limited by a lack of targetable tumor antigens. Most currently targeted antigens have basal expression in healthy tissue, which results in potentially life threatening off-target effects. Moreover, targeting a single antigen alone can lead to the development of therapeutic resistance. A COSMC loss-of-function… Read More