A5101897034- CAR-T cell therapy research
- SARS-CoV-2 and COVID-19 Research
- Computational Drug Discovery Methods
- Immune Cell Function and Interaction
- Angiogenesis and VEGF in Cancer
- Long-Term Effects of COVID-19
- DNA Repair Mechanisms
- Carcinogens and Genotoxicity Assessment
- Molecular Biology Techniques and Applications
- Peptidase Inhibition and Analysis
- Viral Infections and Immunology Research
- Photodynamic Therapy Research Studies
- Biochemical and Molecular Research
- Signaling Pathways in Disease
- Viral gastroenteritis research and epidemiology
- Viral Infections and Outbreaks Research
- Mesenchymal stem cell research
- Ocular Surface and Contact Lens
- CRISPR and Genetic Engineering
- T-cell and B-cell Immunology
- Fibroblast Growth Factor Research
- Immune cells in cancer
- Genomics and Chromatin Dynamics
- Protein Degradation and Inhibitors
- PARP inhibition in cancer therapy
Medpace (United States)
2024
Revolution Medicines (United States)
2023
University of Alberta
2023
Hinge Health
2022
Neoleukin Therapeutics (United States)
2020-2021
Pegatron (Taiwan)
2021
The University of Texas Health Science Center at San Antonio
2018
Fred Hutch Cancer Center
2018
Stanford University
2011-2012
We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins infect the cell. Our pipeline allowed design, validation, and optimization of human angiotensin-converting enzyme 2 (hACE2) neutralize severe acute respiratory syndrome coronavirus (SARS-CoV-2). The best monovalent decoy, CTC-445.2, bound with low nanomolar affinity high specificity receptor-binding domain (RBD) spike protein. Cryo-electron microscopy...
The emergence of severe acute respiratory syndrome coronavirus 2, the causative agent disease 2019, has resulted in largest pandemic recent history. Current therapeutic strategies to mitigate this have focused on development vaccines and drugs that inhibit viral 3CL protease or RNA-dependent RNA polymerase enzymes. A less-explored potentially complementary drug target is Nsp15, a uracil-specific endonuclease shields coronaviruses other nidoviruses from mammalian innate immune defenses. Here,...
There is an urgent need for the ability to rapidly develop effective countermeasures emerging biological threats, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes ongoing disease 2019 (COVID-19) pandemic. We have developed a generalized computational design strategy engineer de novo proteins precisely recapitulate protein surface targeted by agents, like viruses, gain entry into cells. The designed act decoys block cellular and aim be resilient viral...
Germ-line mutations in breast cancer susceptibility gene, BRCA1, result familial predisposition to and ovarian cancers. The BRCA1 protein has multiple functional domains that interact with a variety of proteins cellular processes. Understanding the biological consequences interactions its binding partners is important for elucidating tissue-specific tumor suppression function. Cofactor (COBRA1) BRCA1-binding that, as component negative elongation factor (NELF), regulates RNA polymerase II...
Abstract T cell therapies have had modest efficacy in solid tumors due to their failure proliferate following infusion. We designed a mesothelin (MSLN) CAR product (OPB-101) which includes novel promoter (OP1), an optimized CAR, safety switch, and CD8α-targeted IL-2/15 cytokine promote expansion improve tumors. Human anti-MSLN binders were for the target using our OUTSPACERTM library. evaluation was conducted vitro coculture assays validated NSG tumor xenograft models. OUTSMARTTM avoid...
Abstract A major hurdle for chimeric antigen receptor (CAR) T cells to function in solid tumors is chronic exposure leading terminal lymphocyte exhaustion and impaired anti-tumor activity. Therefore, it necessary establish improved vitro models of antigen-driven CAR cell evaluate new design candidates prior validation with costly vivo studies. Using the human tumor mesothelin (MSLN) MSLN-targeting as a model, we developed two assays that drive an exhausted phenotype can be used predict...
<h3>Background</h3> T cell therapies have shown modest efficacy in solid tumors, including ovarian cancer, due to limited functional persistence. OPB-101 consists of an optimized mesothelin (MSLN) CAR, a CD8α-targeted IL-2 designed cytokine promote expansion, and improved EGFR safety switch. These transgenes are controlled by novel promoter that prevents exhaustion inducibly produces at the site tumor. <h3>Methods</h3> The MSLN CAR humanized anti-MSLN scFv optimal spacer from our OUTSPACER™...
Abstract The KRASG12V mutation is the second most common oncogenic RAS and frequently observed in pancreatic, lung, colorectal cancers. Developing a selective inhibitor of presents significant drug discovery challenges. intrinsic GTP hydrolysis rate about 12-fold lower than that KRASG12C, further biasing cellular pool to active, GTP-bound (“RAS(ON)”) state emphasizing importance targeting KRASG12V(ON) for maximal suppression this driver. Additionally, achieving selectivity over wild-type...
We aim to investigate the prevalence, characteristics and outcomes of COVID-19 patients with neurological manifestations
<h3>Background</h3> NL-201 is a potent, selective, and long-acting computationally designed alpha-independent agonist of the IL-2 IL-15 receptors that being developed as an immunotherapy for cancer. Downregulation MHC class I (MHC-I) expression by tumors well-known mechanism immune escape, IFNγ known to upregulate MHC-I. Here, we investigated whether monotherapy can convert 9cold9 tumor microenvironment (TME) immunologically 9hot9 TME through IFNγ-mediated MHC-I expression. This effect could...