A5006098963- Lung Cancer Treatments and Mutations
- Cancer Mechanisms and Therapy
- Liver physiology and pathology
- Protein Degradation and Inhibitors
- Hepatocellular Carcinoma Treatment and Prognosis
- Hemoglobinopathies and Related Disorders
- Acute Myeloid Leukemia Research
- Synthesis and biological activity
- Enzyme function and inhibition
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- PI3K/AKT/mTOR signaling in cancer
- Renal cell carcinoma treatment
- Iron Metabolism and Disorders
- Chemical Reactions and Isotopes
- Cancer-related Molecular Pathways
- Telomeres, Telomerase, and Senescence
- Neuropeptides and Animal Physiology
- Hematopoietic Stem Cell Transplantation
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Blood groups and transfusion
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Melanoma and MAPK Pathways
- MicroRNA in disease regulation
Dana-Farber Cancer Institute
2010-2025
Harvard University
2020-2025
Shanghai Ninth People's Hospital
2025
Shanghai Jiao Tong University
2023-2025
Rensselaer Polytechnic Institute
2025
Dalian Medical University
2019-2025
Second Affiliated Hospital of Dalian Medical University
2019-2025
Zhuhai People's Hospital
2024
Jinan University
2024
National University of Defense Technology
2024
Abstract Background Control genes, which are often referred to as housekeeping frequently used normalise mRNA levels between different samples. However, the expression level of these genes may vary among tissues or cells and change under certain circumstances. Thus, selection is critical for gene studies. To address this issue, 7 candidate including several commonly ones were investigated in isolated human reticulocytes. For this, a simple ΔCt approach was employed by comparing relative...
Individual variation in fetal hemoglobin (HbF, alpha(2)gamma(2)) response underlies the remarkable diversity phenotypic severity of sickle cell disease and beta thalassemia. HbF levels HbF-associated quantitative traits (e.g., F levels) are highly heritable. We have previously mapped a major trait locus (QTL) controlling an extended Asian-Indian kindred with thalassemia to 1.5-Mb interval on chromosome 6q23, but causative gene(s) not known. The QTL encompasses several genes including HBS1L,...
Abstract Evidence from experimental and clinical studies implicates immuno-inflammatory responses as playing an important role in epilepsy-induced brain injury. Captopril, angiotensin-converting enzyme inhibitor (ACEi), has previously been shown to suppress a variety of neurological diseases. However, the therapeutic potential captopril on epilepsy remains unclear. In present study, Sprague Dawley (SD) rats were intraperitoneally subjected kainic acid (KA) establish status epilepticus....
The transcription factor TEAD, together with its coactivator YAP/TAZ, is a key transcriptional modulator of the Hippo pathway. Activation TEAD by YAP has been implicated in number malignancies, and this complex represents promising target for drug discovery. However, both extensive binding interfaces to have difficult address using small molecules, mainly due lack druggable pockets. post-translationally modified palmitoylation that targets conserved cysteine at central pocket, which provides...
Abstract Activating point mutations in the MET tyrosine kinase domain (TKD) are oncogenic a subset of papillary renal cell carcinomas. Here, using comprehensive genomic profiling among >600,000 patients, we identify activating TKD as putative driver across diverse cancers, with frequency ∼0.5%. The most common defined or likely according to OncoKB resulted amino acid substitutions at positions H1094, L1195, F1200, D1228, Y1230, M1250, and others. Preclinical modeling these alterations...
The ischemic activation of p38α mitogen-activated protein kinase (p38α-MAPK) is thought to contribute myocardial injury. Under other circumstances, through dual phosphorylation by MAPK 3 (MKK3). Therefore, the mkk3 −/− murine heart should be protected during ischemia. In retrogradely perfused and +/+ mouse hearts subjected 30 minutes global ischemia 120 reperfusion, infarction/risk volume was similar (50±5 versus 51±4, P =0.93, respectively), as intraischemic p38-MAPK (10 percent basal,...
Abstract Cyclin‐dependent kinase 2 (CDK2) is a potential therapeutic target for the treatment of cancer. Development CDK2 inhibitors has been extremely challenging as its ATP‐binding site shares high similarity with CDK1, related whose inhibition causes toxic effects. Here, we report development TMX‐2172, heterobifunctional degrader degradation selectivity and CDK5 over not only but transcriptional CDKs (CDK7 CDK9) cell cycle (CDK4 CDK6) well. In addition, demonstrate that antiproliferative...
Abstract Aberrant activation of FGFR signaling occurs in many cancers, and ATP‐competitive inhibitors have received regulatory approval. Despite demonstrating clinical efficacy, these exhibit dose‐limiting toxicity, potentially due to a lack selectivity amongst the family are poorly tolerated. Here, we report discovery characterization DGY‐09‐192, bivalent degrader that couples pan‐FGFR inhibitor BGJ398 CRL2 VHL E3 ligase recruiting ligand, which preferentially induces FGFR1&2...
A systematic strategy to develop dual-warhead inhibitors is introduced circumvent the limitations of conventional covalent such as vulnerability mutations corresponding nucleophilic residue. Currently, all FDA-approved small molecules feature one electrophile, leaving open a facile route acquired resistance. We conducted analysis human proteins in protein data bank reveal ∼400 unique targets amendable dual inhibitors, which we term "molecular bidents". demonstrated this by targeting two...
Common sequence variants situated between the HBS1L and MYB genes on chromosome 6q23.3 (HMIP) influence proportion of F cells (erythrocytes that carry measurable amounts fetal hemoglobin). Since physiological processes underlying F-cell variability are thought to be linked kinetics erythrocyte maturation differentiation, we have investigated HMIP locus other hematologic parameters. Here show a significant impact several types peripheral blood cells: erythrocyte, platelet, monocyte counts as...
It has been suggested that altered levels or function of alpha-haemoglobin stabilising protein (AHSP), an erythroid-specific binds specifically to free alpha-(haemo)globin, might account for some the clinical variability in beta-thalassaemia. To assess variation AHSP expression, mRNA circulating reticulocytes 103 healthy individuals were measured by quantitative reverse transcription-polymerase chain reaction. expression varied up threefold, and did not correlate with age sex. A systematic...
SRC is a major regulator of many signaling pathways and contributes to cancer development. However, development selective inhibitor has been challenging, FDA-approved inhibitors, dasatinib bosutinib, are multitargeted kinase inhibitors. Here, we describe our efforts develop covalent by targeting cysteine 277 on the P-loop SRC. Using promiscuous (CKI) SM1-71 as starting point, developed 15a, which discriminates from other targets including TAK1 FGFR1. As an irreversible inhibitor, compound...
Abstract Oncogenic translocations involving the MET gene have been reported in several cancer types, but detailed clinicogenomic characterization of these cancers is not well defined. In addition, prospective clinical trials evaluating antitumor activity inhibitors rearrangement-positive are limited. Here, a pan-cancer analysis >46,000 solid tumors with comprehensive genomic profiling, we identified oncogenic rearrangements ~0.04% cancers. Preliminary from phase 2 trial type I...