A5071835523- Cancer-related Molecular Pathways
- Advanced Breast Cancer Therapies
- Breast Cancer Treatment Studies
- PI3K/AKT/mTOR signaling in cancer
- Cell Image Analysis Techniques
- Cancer Treatment and Pharmacology
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- PARP inhibition in cancer therapy
- Cancer Research and Treatments
- Mathematical Biology Tumor Growth
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- HER2/EGFR in Cancer Research
- Calcium signaling and nucleotide metabolism
- Single-cell and spatial transcriptomics
- Chronic Lymphocytic Leukemia Research
- Ion channel regulation and function
- Insect Resistance and Genetics
- Retinoids in leukemia and cellular processes
- interferon and immune responses
- Signaling Pathways in Disease
- CRISPR and Genetic Engineering
- Metabolism, Diabetes, and Cancer
- Protein Tyrosine Phosphatases
Dana-Farber Cancer Institute
2016-2025
Broad Institute
2020-2025
Harvard University
2017-2025
Cancer Genetics (United States)
2023
Massachusetts Institute of Technology
2021
Boston University
2010-2018
Dana-Farber/Harvard Cancer Center
2018
State Key Laboratory of Biotherapy
2013-2017
Sichuan University
2013-2017
University School
2012
PARP inhibitors (PARPi) have drastically changed the treatment landscape of advanced ovarian tumors with BRCA mutations. However, impact this class in patients BRCA-mutant breast cancer is relatively modest. Using a syngeneic genetically-engineered mouse model tumor driven by Brca1 deficiency, we show that tumor-associated macrophages (TAMs) blunt PARPi efficacy both vivo and vitro. Mechanistically, BRCA1-deficient cells induce pro-tumor polarization TAMs, which turn suppress PARPi-elicited...
Summary Cellular senescence, which is known to halt proliferation of aged and stressed cells, plays a key role against cancer development also closely associated with organismal aging. While increased insulin‐like growth factor ( IGF ) signaling induces cell proliferation, survival progression, disrupted enhance longevity concomitantly delay in aging processes. The molecular mechanisms involved the regulation by whether regulates cellular senescence are still poorly understood. In this...
Cancer patients frequently develop chemotherapy-induced peripheral neuropathy (CIPN), a painful and long-lasting disorder with profound somatosensory deficits. There are no effective therapies to prevent or treat this disorder. Pathologically, CIPN is characterized by “dying-back” axonopathy that begins at intra-epidermal nerve terminals of sensory neurons progresses in retrograde fashion. Calcium dysregulation constitutes critical event CIPN, but it not known how chemotherapies such as...
Resistance to endocrine therapy (ET) and CDK4/6 inhibitors (CDK4/6i) is a clinical challenge in estrogen receptor (ER)-positive (ER+) breast cancer. Cyclin-dependent kinase 7 (CDK7) candidate target endocrine-resistant ER+ cancer models selective CDK7 (CDK7i) are development for the treatment of Nonetheless, precise mechanisms responsible activity CDK7i remain elusive. Herein, we sought unravel these mechanisms.
This study presents strategies to render triple-negative breast cancers sensitive CDK4/6 inhibitors.
There is growing interest in developing non-pharmacological treatments that could boost natural defenses against cancer and contribute to primary secondary prevention. Recent studies have shown gentle daily stretching for 10 minutes can reduce local connective tissue inflammation fibrosis. Because mechanical factors within the stroma influence tumor microenvironment, we hypothesized would growth of tumors implanted locally stretched tissues tested this hypothesis a mouse orthotopic breast...
Significance Oncogenic hotspot mutations in PIK3CA or RAS and overexpression of Her2 are known as a driving force for human cancer development. We others have shown that ΔNp63α, the major protein isoform p53-related p63 expressed epithelial cells, functions an important regulator cell adhesion program is critical inhibitor metastasis. In this study, we demonstrate oncogenic p110α H1047R , K-Ras G12V H-Ras use common Akt1-FOXO3a pathway suppression ΔNp63α expression and, consequently, promote...
P63 is a p53 family member involved in multiple facets of biology, including embryonic development, cell proliferation, differentiation, survival, apoptosis, senescence and aging. The p63 gene encodes protein isoforms either with (TAp63) or without (ΔNp63) the N-terminal transactivation domain. Amounting evidence suggests that can function as tumor suppressor, yet precise molecular mechanisms, particularly specific roles TAp63 ΔNp63 cancer progression, are still largely unclear. Here, we...
Abstract Inactivation of the retinoblastoma protein (Rb) has a key role in tumorigenesis. It is well established that Rb function largely regulated by dynamic balance phosphorylation and dephosphorylation. Although much research been done to understand mechanisms RB phosphorylation, regulation dephosphorylation still not understood. In this study, we demonstrate Pin1 an important cell cycle progression S-phase checkpoint upon DNA damage. We show C-pocket directly binds WW domain vitro vivo ,...
Highlights•p53/p73 are key for DNA damage-induced apoptosis but not G2/M arrest in mESCs•Both p53 and p73 required differentiation-induced mESCs•Doxorubicin induces RB via p53-mediated suppression of miR-17-92 miR-106a-363•p73 expression is induced upon differentiation mESCsSummaryEmbryonic stem cells (ESCs) fast proliferating capable differentiating into all somatic cell types. In cells, it well documented that rapidly activated damage to the cycle induce apoptosis. mouse ESCs, can also be...
Aim: To assess several fabrication metrics of a 3D-printed smartphone-attachable continuous-flow magnetic focusing device for real-time separation and detection different cell types based on their volumetric mass density in high-volume samples. Method: The smartphone apparatus has been designed fabricated using three 3D printing method. Several including cost, time, resolution have evaluated to propose cost-efficient high-performance platform low-resource settings. Results: apply the...
Vincristine is extensively used chemotherapeutic medicine to treat leukemia. However, it remains a critical clinical problem with regard its toxicity and drug-resistance. AMP-activated protein kinase (AMPK) an energy sensor that pivotal in maintaining cell metabolic homeostasis. It reported AMPK involved vincristine-induced apoptosis. whether chemotherapy-resistance largely unclear. well-documented metformin, widely type II diabetes, possesses anti-cancer activities, yet metformin affects...
Abstract The p53 homologue p63 encodes multiple protein isoforms either with (TA) or without (ΔN) the N‐terminal transactivation domain. Accumulating evidence indicates that TAp63 plays an important role in various biological processes, including cell proliferation, differentiation, and apoptosis. However, how is regulated remains largely unclear. In this study, we demonstrate NF‐κB induces gene expression. responsible elements for NF‐κB‐mediated induction are located within region from −784...
The Murine Double Minute 2 (MDM2) protein is a key regulator of cell proliferation and apoptosis that acts primarily by inhibiting the p53 tumor suppressor. Similarly, PI3-Kinase (PI3K)/AKT pathway critical for growth factor-mediated survival. Additionally, it has been reported AKT can directly phosphorylate activate MDM2. In this study, we show IGF-1 up-regulates MDM2 levels in PI3K/AKT-dependent manner. Inhibition mTOR rapamycin or expression dominant negative eukaryotic initiation factor...