A5067248001- Protein Tyrosine Phosphatases
- Monoclonal and Polyclonal Antibodies Research
- Zebrafish Biomedical Research Applications
- Axon Guidance and Neuronal Signaling
- Chronic Lymphocytic Leukemia Research
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Phagocytosis and Immune Regulation
- Developmental Biology and Gene Regulation
- PI3K/AKT/mTOR signaling in cancer
- RNA Research and Splicing
- Hepatitis C virus research
- Neurogenesis and neuroplasticity mechanisms
- Advanced Breast Cancer Therapies
- Hepatitis B Virus Studies
- Glioma Diagnosis and Treatment
- Cancer Treatment and Pharmacology
- HER2/EGFR in Cancer Research
- Retinoids in leukemia and cellular processes
- Acute Lymphoblastic Leukemia research
- Liver Disease Diagnosis and Treatment
- Reproductive System and Pregnancy
- Protein Degradation and Inhibitors
- Lung Cancer Treatments and Mutations
- Multiple Myeloma Research and Treatments
Gilead Sciences (United States)
2021-2024
Bristol-Myers Squibb (United States)
2022
Exelixis (United States)
2008-2010
Max Planck Society
1996-1997
Max Planck Institute for Developmental Biology
1996-1997
Cancer Research UK
1996
ABSTRACT Zebrafish embryos and larvae have stage-specific patterns of motility or locomotion. Two embryonic structures accomplish this behavior: the central nervous system (CNS) skeletal muscles. To identify genes that are functionally involved in mediating controlling different larval motility, we included a simple touch response test our zebrafish large-scale genetic screen. In total identified 166 mutants with specific defects motility. These fall into 14 phenotypically distinct groups...
Jaws and branchial arches together are a basic, segmented feature of the vertebrate head. Seven develop in zebrafish embryo (Danio rerio), derived largely from neural crest cells that form cartilaginous skeleton. In this following paper we describe phenotypes 109 arch mutants, focusing here on three classes affect posterior pharyngeal arches, including hyoid five gill-bearing arches. lockjaw, is strongly reduced subsets do not develop. Mutants large second class, designated flathead group,...
We have isolated mutants in the zebrafish Danio rerio that defects axonal connectivity between retina and tectum. 5-day-old fish larvae were screened by labeling retinal ganglion cells with DiI DiO observing their projections to on 82 mutations, representing 13 complementation groups 6 single allele loci, found cell axon pathfinding These genes fall into five classes, based location of errors eye In Class I mutant (belladonna, detour, you-too, iguana, umleitung, blowout) axons grow directly...
Retinoic acid (RA) plays important roles in diverse biological processes ranging from germ cell specification to limb patterning. RA ultimately exerts its effect the nucleus, but how levels are being generated and maintained locally is less clear. Here, we have analyzed zebrafish stocksteif mutant, which exhibits severe over-ossification of entire vertebral column. encodes cyp26b1, a cytochrome P450 member that metabolizes RA. The mutant completely phenocopied by treating 4 dpf wild-type...
A systematic search for mutations affecting the retinotectal projection in zebrafish larvae was performed, as part of large-scale Tubingen screen homozygous diploid mutants embryonic development. 2,746 inbred lines (F2 families) from males mutagenized with ethylnitroso urea were screened. In wild-type larvae, developing retinal axons travel along a stereotyped route to contralateral optic tectum. Here, their terminals form highly ordered retinotopic map. To detect deviations this pattern, an...
Retinal ganglion cells connect to their target organ, the rectum, in a highly ordered fashion. We performed large-scale screen for mutations affecting retinotectal projection of zebrafish, which resulted identification 114 mutations. 44 these disturb either order RGC axons optic nerve and tract, establishment topographic map on tectum, or formation proper termination fields. Mutations three genes, boxer, dackel pinscher, disrupt sorting tract but do not affect mapping tectum. In mutants,...
Mutations associated with resistance to kinase inhibition are an important mechanism of intrinsic or acquired loss clinical efficacy for kinase-targeted therapeutics. We report the prospective discovery ErbB2 mutations that confer small-molecule inhibitor lapatinib.We did in vitro screening using a randomly mutagenized expression library Ba/F3 cells, which were dependent on activity survival and growth.Lapatinib screens identified at 16 different amino acid residues, 12 mutated acids mapping...
GS-3583, an FMS-like tyrosine kinase 3 (FLT3) agonist Fc fusion protein, expanded conventional dendritic cells (cDC) in the periphery of healthy volunteers, suggesting potential for GS-3583 to increase cDCs tumor microenvironment and promote T cell-mediated antitumor activity cancer patients. This phase Ib open-label study assessed adults with advanced solid tumors.
•We applied a novel imaging technique to quantify HBsAg and HBV core antigen burden in liver biopsies from patients with CHB.•The frequency of core+ hepatocytes was lower HBeAg-negative participants than HBeAg-positive participants.•NUC treatment associated significant decline cells but not HBsAg.•Duplicate collected at the same time point revealed large local variation staining within participants.•HBV+ hepatocyte correlated HBcrAg, DNA, RNA only baseline. Background & AimsPatterns...
2505 Background: CC-115 is a potent inhibitor of DNA-PK and TOR kinase (DNA-PKi/TORKi) with broad pre-clinical anti-tumor activity. Methods: Subjects relapsed/refractory advanced solid hematologic cancers enrolled in first-in-human Phase 1a/b study given orally once or twice daily until disease progression dose escalation expansion cohorts. Results: 44 subjects evaluated across 10 cohorts (0.5 – 40 mg) established mg twice-daily (BID) as the recommended for cohort 62 additional glioblastoma...
Abstract Conventional dendritic cells subtype 1 (cDC1) play a vital role in the priming and expansion of tumor‐specific CD8+ T their recruitment to tumor microenvironment. However, cDC1s are often underrepresented Systemic administration Fms‐like tyrosine kinase 3 ligand, hematopoietic growth factor that binds FLT3 on myeloid lymphoid progenitor cells, leads cDC1 periphery into pathway stimulation using GS‐3583, novel agonistic Fc fusion protein, has potential promote T‐cell mediated...
Early data suggested that CC-115, a clinical molecule, already known to inhibit the mammalian target of rapamycin kinase (TORK) and DNA-dependent protein (DNA-PK) may have additional targets beyond TORK DNA-PK. Therefore, we aimed identify such target(s) investigate potential therapeutic applicability. Functional profiling 141 cancer cell lines revealed inhibition suppressor morphogenesis in genitalia 1 (SMG1), key regulator RNA degradation mechanism nonsense-mediated mRNA decay (NMD), as an...
2559 Background: Conventional dendritic cells subtype 1 (cDC1) play a vital role in the priming and expansion of tumor specific CD8+ T their recruitment to microenvironment (TME). However, cDC1s are often underrepresented TME. Systemic administration Fms-like tyrosine kinase 3 ligand (FLT3L), hematopoietic growth factor that binds FLT3 on myeloid lymphoid progenitor cells, leads periphery which can then be recruited into We hypothesize pathway stimulation using GS-3583, agonist Fc fusion...
2566 Background: We have previously shown that systemic administration of GS-3583, a Fms-like tyrosine kinase 3 (FLT3) agonist Fc fusion protein leads to expansion conventional dendritic cells (cDC), both subtype 1 (cDC1) and 2 (cDC2), in the periphery healthy volunteers (Rajakumaraswamy N, et al. J Clin Oncol. 2021;39[suppl_15]:2559.). This mechanism may increase cDC tumor microenvironment promote T cell mediated antitumor activity patients with solid tumors. Methods: ongoing, Phase 1b,...
<div>AbstractPurpose:<p>GS-3583, an FMS-like tyrosine kinase 3 (FLT3) agonist Fc fusion protein, expanded conventional dendritic cells (cDC) in the periphery of healthy volunteers, suggesting potential for GS-3583 to increase cDCs tumor microenvironment and promote T cell–mediated antitumor activity cancer patients. This phase Ib open-label study assessed adults with advanced solid tumors.</p>Patients Methods:<p>Multiple escalating doses (standard 3+3 design) were...
<div>AbstractPurpose:<p>GS-3583, an FMS-like tyrosine kinase 3 (FLT3) agonist Fc fusion protein, expanded conventional dendritic cells (cDC) in the periphery of healthy volunteers, suggesting potential for GS-3583 to increase cDCs tumor microenvironment and promote T cell–mediated antitumor activity cancer patients. This phase Ib open-label study assessed adults with advanced solid tumors.</p>Patients Methods:<p>Multiple escalating doses (standard 3+3 design) were...
<p>Concentration vs. time profiles of GS-3583. Mean ± standard deviation GS-3583 serum concentration profile in patients with solid tumors. A. Log-linear scale; B. Linear scale. The lower limit quantification was 5 ng/mL.</p>
<p>White blood cell counts of patients in the 20-mg cohort over time.</p>
<p>Concentration vs. time profiles of GS-3583. Mean ± standard deviation GS-3583 serum concentration profile in patients with solid tumors. A. Log-linear scale; B. Linear scale. The lower limit quantification was 5 ng/mL.</p>
<p>White blood cell counts of patients in the 20-mg cohort over time.</p>
<p>Patient flow (participant disposition)</p>