Valley fever or coccidioidomycosis is a pulmonary infection caused by species of Coccidioides fungi that are endemic to California and Arizona. Skeletal coccidioidomycosis accounts for about half of disseminated infections, with the vertebral spine being the preferred site of dissemination. Most cases of skeletal coccidioidomycosis progress to bone...
Effective and safe therapies for the treatment of diseases caused by intraerythrocytic parasites are impeded by the rapid emergence of drug resistance and the lack of novel drug targets. One such disease is human babesiosis, which is a rapidly emerging tick-borne illness caused by Babesia parasites. In this study, we identified fosinopril, a phosph...
Pancreatic ductal adenocarcinoma (PDAC), a highly lethal disease with limited therapeutic options, may benefit from repurposing of FDA-approved drugs in preventive or interceptive strategies in high-risk populations. Previous animal studies demonstrated that the use of metformin and statins as single agents at relatively high doses restrained PDAC ...
Glioblastoma (GBM), the most common primary malignant brain tumor, is a highly lethal form of cancer with a very limited set of treatment options. High heterogeneity in the tumor cell population and the invasive nature of these cells decrease the likely efficacy of traditional cancer treatments, thus requiring research into novel treatment options....
Tuberculosis (TB) is an airborne disease caused by Mycobacterium tuberculosis (Mtb). Whilst a functional role for humoral immunity in Mtb protection remains poorly defined, previous studies have suggested that antibodies can contribute towards host defense. Thus, identifying the critical components in the antibody repertoires from immune, chronical...
Acknowledgements: KMP acknowledges funding from the Catalan Institution for Research and Advanced Studies (ICREA), the European Research Council (ERC) through ERC-CoG PHOTHERM, and the European Union project ESiM 101046364. The Swedish NMR Centre at the University of Gothenburg is acknowledged for its support. / To achieve the ultimate limit of dev...
Molecularly targeted radionuclide therapies (TRTs) struggle with balancing efficacy and safety, as current strategies to increase tumor absorption often alter drug pharmacokinetics to prolong circulation and normal tissue irradiation. Here we report the first covalent protein TRT, which, through reacting with the target irreversibly, increases radi...
Radical cure of Plasmodium vivax malaria must include elimination of quiescent "hypnozoite" forms in the liver; however, the only FDA-approved treatments are contraindicated in many vulnerable populations. To identify new drugs and drug targets, we screened the Repurposing, Focused Rescue, and Accelerated Medchem library against P. vivax liver stag...
RNA therapeutics have had a tremendous impact on medicine, recently exemplified by the rapid development and deployment of mRNA vaccines to combat the COVID-19 pandemic. In addition, RNA-targeting drugs have been developed for diseases with significant unmet medical needs through selective mRNA knockdown or modulation of pre-mRNA splicing. Recently...
Immunotherapies, such as immune checkpoint inhibitors, cellular therapies, and T-cell engagers, have fundamentally changed our approach to treating cancer. However, successes with cancer vaccines have been more difficult to realize. While vaccines against specific viruses have been widely adopted to prevent the development of cancer, only two vacci...
