Nanhua Deng
A5010287617- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Cytokine Signaling Pathways and Interactions
- Renal and related cancers
- CRISPR and Genetic Engineering
- Animal Genetics and Reproduction
- Immune Cell Function and Interaction
- RNA modifications and cancer
- DNA Repair Mechanisms
- Adenosine and Purinergic Signaling
- Biochemical Analysis and Sensing Techniques
- interferon and immune responses
- Phagocytosis and Immune Regulation
- Peptidase Inhibition and Analysis
- Cancer-related gene regulation
- Advanced Biosensing Techniques and Applications
- Cancer Genomics and Diagnostics
- Cancer Mechanisms and Therapy
- Click Chemistry and Applications
- Reproductive System and Pregnancy
- Digestive system and related health
- Biochemical and Molecular Research
- Protease and Inhibitor Mechanisms
- Chronic Lymphocytic Leukemia Research
AstraZeneca (United States)
2015-2020
Kala Pharmaceuticals (United States)
2015-2017
Nanyang Medical College
2014
AVEO Oncology (United States)
2010
Millennium Engineering and Integration (United States)
1995-1997
We have identified a novel cDNA encoding protein highly homologous to the mammalian brown fat uncoupling (UCP). Unlike known UCP, which is expressed specifically in adipose tissue, UCP homolog (UCPH) mRNA variety of tissues, with predominant expression human white tissue and skeletal muscle. In ob/ob db/db mice, UCPH transcript induced approximately fivefold relative lean littermate controls. Expression murine yeast results growth inhibition under conditions that require aerobic respiration,...
Polycystin, the product of autosomal dominant polycystic kidney disease (ADPKD) 1 gene (PKD1) is cardinal member a novel class proteins. As first step towards elucidating function polycystin and pathogenesis ADPKD, three types information were collected in current study: subcellular localization polycystin, spatial temporal distribution protein within normal tissues effects ADPKD mutations on pattern expression affected tissues. Antisera directed against synthetic peptide two recombinant...
Accumulation of extracellular adenosine within the microenvironment is a strategy exploited by tumors to escape detection immune system. Adenosine signaling through 2A receptor (A2AR) on cells elicits range immunosuppressive effects which promote tumor growth and limit efficacy checkpoint inhibitors. Preclinical data with A2AR inhibitors have demonstrated regressions in mouse models rescuing T cell function; however, mechanism role other has not been fully elucidated.We report here...
Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due expanded DNA (TA)n dinucleotide repeats. is a promising synthetic lethal target for MSI tumors, and inhibitors are in development. In this study, we used CRISPR-Cas9 base editing map residues critical cells, validating the domain as primary drug target. Fragment-based screening led development of potent highly selective covalent inhibitors. These compounds selectively suppressed model growth vitro...
JAK1, JAK2, JAK3, and TYK2 belong to the JAK (Janus kinase) family. They play critical roles in cytokine signaling. Constitutive activation of JAK/STAT pathways is associated with a wide variety diseases. Particularly, pSTAT3 observed response treatment inhibitors oncogenic signaling such as EGFR, MAPK, AKT resistance or poorer agents targeting these pathways. Among family kinases, JAK1 has been shown be primary driver STAT3 phosphorylation signaling; therefore, selective inhibition can...
Danvatirsen is a therapeutic antisense oligonucleotide (ASO) that selectively targets STAT3 and has shown clinical activity in two phase I studies. We interrogated the mechanism of action using danvatirsen-treated patient samples conducted back-translational studies to further elucidate its immunomodulatory action.Paired biopsies blood from patients were evaluated immunohistochemistry gene-expression analysis. To gain mechanistic insight, we used mass cytometry, flow immunofluorescence...
Abstract Accumulation of extracellular adenosine within the microenvironment is a strategy exploited by tumors to escape immunosurveillance. Adenosine signaling through high affinity 2A receptor (A2AR) on immune cells elicits range immunosuppressive effects which can promote tumor growth and limit efficacy checkpoint inhibitors such as anti-PD-1 or anti-PD-L1 Abs. AZD4635 (HTL-1071), an oral A2AR antagonist, binds human with Ki 1.7 nM > 30-fold selectivity over other receptors....
Abstract Adenosine signaling through the high affinity adenosine 2A receptor (A2AR) on immune cells elicits a range of immunosuppressive effects which can promote tumor growth and limit efficacy checkpoint inhibitors. AZD4635 (HTL-1071) is potent selective oral A2AR antagonist, currently in Phase 1 clinical trial as single agent combination with durvalumab (anti-PD-L1 Ab) patients solid malignancies. In functional vitro assays, IC50 for inhibition dependent concentrations ranges from 1,...
Abstract Microsatellite-unstable (MSI) cancers depend on the WRN helicase to resolve replication stress from expanded (TA)-dinucleotide repeats. is a promising synthetic lethal target for MSI tumours and inhibitors are being developed. Here, we used CRISPR-Cas9 base editing map residues critical lethality, validating domain as primary guiding inhibitor discovery. Fragment-based screening led discovery of potent highly selective covalent same chemical series. These compounds strikingly...
<p>Supplementary Figure 1. Generating base editor-expressing MSI cell lines for screening. Supplementary 2. Quality control base-editor screens in lines. 3. Discovery and characterization of novel inhibitors WRN helicase. 4. Correlation inhibitor sensitivity with genetic molecular markers models. 5. Comparative analysis DNA damage MSS cells treated inactivation. 6: Effects GSK_WRN4 on colorectal cancer xenografts.</p>
<p>This table lists the results from Base editing screen</p>
<p>This file contains details of the BE sgRNA library</p>
<p>This file contain information on the Cell lines and organoids used in this study</p>
<div>Abstract<p>Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due expanded DNA (TA)<sub>n</sub> dinucleotide repeats. is a promising synthetic lethal target for MSI tumors, and inhibitors are in development. In this study, we used CRISPR–Cas9 base editing map residues critical cells, validating the domain as primary drug target. Fragment-based screening led development of potent highly selective covalent inhibitors. These...
<p>Supplementary Figure 1. Generating base editor-expressing MSI cell lines for screening. Supplementary 2. Quality control base-editor screens in lines. 3. Discovery and characterization of novel inhibitors WRN helicase. 4. Correlation inhibitor sensitivity with genetic molecular markers models. 5. Comparative analysis DNA damage MSS cells treated inactivation. 6: Effects GSK_WRN4 on colorectal cancer xenografts.</p>
<p>This file contain information on the Cell lines and organoids used in this study</p>
<p>This table lists the results from Base editing screen</p>
<p>This file contains details of the BE sgRNA library</p>
<div>Abstract<p>Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due expanded DNA (TA)<sub>n</sub> dinucleotide repeats. is a promising synthetic lethal target for MSI tumors, and inhibitors are in development. In this study, we used CRISPR–Cas9 base editing map residues critical cells, validating the domain as primary drug target. Fragment-based screening led development of potent highly selective covalent inhibitors. These...
Abstract EGFR kinase inhibitors have provided tremendous benefit for non-small cell lung cancer (NSCLC) patients with driver mutations. However, many fail to respond or responses of limited duration. Accumulating evidence suggests that the JAK1/STAT3 axis plays a role in tumor escape, and combined inhibition JAK1 may drive more complete durable responses. Here we report AZD4205, potent ATP-competitive inhibitor inhibits Ki 2.8 nM exhibits excellent selectivity vs. other JAK family kinases...
Abstract AZD9150 is a gen2.5 antisense oligonucleotide (ASO) targeting STAT3. Gen2.5 ASOs exhibit enhanced drug-like properties compared to previous generations of therapeutics, including increased stability and resistance nucleases, marked decrease in proinflammatory effects, potency. The immune suppressive effects STAT3 signaling are well established (Kortylewski et al.; Nat. Med. 2005 Curr. Opin. Immunol. 2008). Preclinical experiments were carried out determine the potential for...
Abstract AZD9150, a gen2.5 antisense oligonucleotide (ASO) targeting human STAT3, has improved drug-like properties compared to previous generation ASO therapeutics, including increased stability and resistance nucleases, reduced proinflammatory effects, enhanced potency. We have previously reported that in tumors, STAT3 ASOs are taken up preferentially stromal immune cells of the tumor microenvironment (TME). Since AZD9150 is selective for we used surrogate (muSTAT3 ASO) explore...