A5005257192- Cancer Immunotherapy and Biomarkers
- Ovarian cancer diagnosis and treatment
- Bladder and Urothelial Cancer Treatments
- Cell Adhesion Molecules Research
- Parkinson's Disease Mechanisms and Treatments
- Nanopore and Nanochannel Transport Studies
- Immunotherapy and Immune Responses
- Amyotrophic Lateral Sclerosis Research
- Biochemical and Structural Characterization
- RNA Interference and Gene Delivery
- Microfluidic and Capillary Electrophoresis Applications
- Membrane-based Ion Separation Techniques
- Drug Transport and Resistance Mechanisms
- Radiopharmaceutical Chemistry and Applications
- Immune Cell Function and Interaction
- Lysosomal Storage Disorders Research
- Immune Response and Inflammation
- Click Chemistry and Applications
- Molecular Biology Techniques and Applications
- Nanoparticle-Based Drug Delivery
- Alzheimer's disease research and treatments
- Peptidase Inhibition and Analysis
- Membrane Separation Technologies
- DNA Repair Mechanisms
- Transgenic Plants and Applications
Denali Therapeutics (United States)
2020-2025
Stanford University
2015-2024
Bioengineering Center
2021
Stanford Medicine
2020-2021
University of California, Santa Cruz
2010-2012
Coupling nucleic acid processing enzymes to nanoscale pores allows controlled movement of individual DNA or RNA strands that is reported as an ionic current/time series. Hundreds enzyme complexes can be examined in single-file order at high bandwidth and spatial resolution. The bacteriophage phi29 polymerase (phi29 DNAP) attractive candidate for this technology, due its remarkable processivity affinity substrates. Here we show DNAP−DNA are stable when captured electric field across the...
Brain exposure of systemically administered biotherapeutics is highly restricted by the blood-brain barrier (BBB). Here, we report engineering and characterization a BBB transport vehicle targeting CD98 heavy chain (CD98hc or SLC3A2) heterodimeric amino acid transporters (TVCD98hc). The pharmacokinetic biodistribution properties CD98hc antibody (ATVCD98hc) are assessed in humanized knock-in mice cynomolgus monkeys. Compared to most existing platforms transferrin receptor, peripherally...
Abstract Purpose: Ovarian cancer represents a major clinical hurdle for immune checkpoint blockade (ICB), with reported low patient response rates. We found that the ligand PD-L2 is robustly expressed in samples of ovarian cancers and other malignancies exhibiting suboptimal to ICB but not are sensitive. Therefore, we hypothesize can facilitate escape from through incomplete PD-1 signaling pathway. Experimental Design: engineered soluble form receptor (sPD-1) capable binding neutralizing...
Abstract The RGD (Arg-Gly-Asp)-binding integrins αvβ6 and αvβ8 are clinically validated cancer fibrosis targets of considerable therapeutic importance. Compounds that can discriminate between homologous other integrins, stabilize specific conformational states, have high thermal stability could utility. Existing small molecule antibody inhibitors do not all these properties, hence new approaches needed. Here we describe a generalized method for computationally designing RGD-containing...
Targeting proteins highly expressed at the blood-brain barrier, including transferrin receptor (TfR) and CD98hc, is a transformative approach enabling more effective brain delivery of biotherapeutics for treatment neurological diseases. TfR-mediated promotes rapid, high uptake, while CD98hc-mediated slower with prolonged exposure. Here, we engineer huIgG Fc domain to bind both TfR CD98hc create dual transport vehicle (TV) platform that drives distinct properties. Dual TVs achieve...
Complexes of phi29 DNA polymerase and fluctuate on the millisecond time scale between two ionic current amplitude states when captured atop α-hemolysin nanopore in an applied field. The lower state is stabilized by complementary dNTP thus corresponds to complexes post-translocation state. We have demonstrated that upper state, displaced a distance one nucleotide from propose pre-translocation Force exerted template strand biases toward Based results voltage titrations, we concluded through...
<div>AbstractPurpose:<p>Ovarian cancer represents a major clinical hurdle for immune checkpoint blockade (ICB), with reported low patient response rates. We found that the ligand PD-L2 is robustly expressed in samples of ovarian cancers and other malignancies exhibiting suboptimal to ICB but not are sensitive. Therefore, we hypothesize can facilitate escape from through incomplete PD-1 signaling pathway.</p>Experimental Design:<p>We engineered soluble form receptor...
<p>Supplementary data, material methods and table</p>
<p>Supplementary data, material methods and table</p>
<div>AbstractPurpose:<p>Ovarian cancer represents a major clinical hurdle for immune checkpoint blockade (ICB), with reported low patient response rates. We found that the ligand PD-L2 is robustly expressed in samples of ovarian cancers and other malignancies exhibiting suboptimal to ICB but not are sensitive. Therefore, we hypothesize can facilitate escape from through incomplete PD-1 signaling pathway.</p>Experimental Design:<p>We engineered soluble form receptor...
Abstract Urokinase‐type plasminogen activator receptor (uPAR) is overexpressed on tumor cells in multiple types of cancer and contributes to disease progression metastasis. In this work, we engineered a novel bi‐paratopic uPAR targeting agent by fusing the binding domains two native ligands: uPA vitronectin, with flexible peptide linker. The linker length was optimized facilitate simultaneous engagement both their adjacent epitopes uPAR, resulting high affinity avid interaction. Furthermore,...
Abstract Background Heterozygous loss of function (LOF) mutations in GRN cause frontotemporal dementia (FTD), a neurodegenerative disorder associated with lysosomal dysfunction, TDP‐43 pathology and inflammation the CNS. Additionally, homozygous LOF neuronal ceroid lipofuscinosis, storage disorder. encodes progranulin (PGRN), soluble protein that is most abundantly expressed microglia, where it localizes to lysosomes can undergo secretion. Although precise PGRN unknown, growing evidence...
Abstract The RGD (Arg-Gly-Asp)-binding integrins αvβ6 and αvβ8 are clinically validated cancer fibrosis targets of considerable therapeutic importance. Compounds that can discriminate between the two closely related integrin proteins other integrins, stabilize specific conformational states, have sufficient stability enabling tissue restricted administration could utility. Existing small molecules antibody inhibitors do not all these properties, hence there is a need for new approaches. Here...
Abstract Immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have improved for a number of solid tumors. Unfortunately, ovarian cancer represents major clinical hurdle immune blockade (ICB) with reported low patient response rates. Using IHC staining, we find that PD-L2 is highly expressed in cancers and other malignancies sub-optimal to ICB, at levels responsive ICB. Based on this observation, hypothesized elevated expression produced by both tumor surrounding stromal cells...
We describe the de novo design of hyperstable inhibitory proteins that bind to human αvβ6 with sub-nanomolar affinity and >1000x specificity over other RGD (Arg-Gly-Asp)-binding integrins. The crystal structure inhibitor closely matches model, arising not only from an RGDLXX(L/I)-containing loop but also a second contacts β6 subunit. designed blocks -mediated TGF-β signalling in vitro specifically targets (+) tumors vivo. When administered via intraperitoneal injection or as inhaled...