A5085001212- Cardiac Fibrosis and Remodeling
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Histone Deacetylase Inhibitors Research
- GDF15 and Related Biomarkers
- Nuclear Receptors and Signaling
- Apelin-related biomedical research
- Genetic factors in colorectal cancer
- Colorectal Cancer Treatments and Studies
- Cancer Research and Treatments
- Cancer Genomics and Diagnostics
- Gastric Cancer Management and Outcomes
- Cancer-related Molecular Pathways
- FOXO transcription factor regulation
- Peptidase Inhibition and Analysis
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Genetic Syndromes and Imprinting
- Nutrition, Genetics, and Disease
- Microtubule and mitosis dynamics
- Mechanisms of cancer metastasis
- TGF-β signaling in diseases
- Radiomics and Machine Learning in Medical Imaging
- RNA modifications and cancer
- Cholangiocarcinoma and Gallbladder Cancer Studies
AstraZeneca (United States)
2023-2025
Whitehead Institute for Biomedical Research
2017-2024
Boston University
2010-2020
Massachusetts Institute of Technology
2020
Harvard University
2011
Beth Israel Deaconess Medical Center
2011
University of Alabama at Birmingham
2010
Anti-inflammatories prevent surgery-induced outgrowth of distant tumors in mouse models and may reduce early metastatic relapse patients.
Abstract SMAD4 is localized to chromosome 18q21, a frequent site for loss of heterozygosity in advanced stage colon cancers. Although Smad4 regarded as signaling mediator the TGFβ pathway, its role major suppressor colorectal cancer progression and molecular events underlying this phenomenon remain elusive. Here, we describe establishment use cell line model systems dissect functional roles inactivation manifestation malignant phenotype. We found that function retention intact receptors...
Breast cancer progression is associated with aberrant DNA methylation and expression of genes that control the epithelial-mesenchymal transition (EMT), a critical step in malignant conversion. Although affected have been studied, there little understanding how activation machinery itself occurs. Using breast cell-based model system, we found cells underwent EMT exhibited overactive transforming growth factor beta (TGFbeta) signaling loss CDH1, CGN, CLDN4, KLK10 as result hypermethylation...
Basal-like breast cancer (BLBC) is an aggressive subtype often characterized by distant metastasis, poor patient prognosis, and limited treatment options. Therefore, the discovery of alternative targets to restrain its metastatic potential urgently needed. In this study, we aimed identify novel genes that drive metastasis BLBC elucidate underlying mechanisms action.An unbiased approach using gene expression profiling a progression model in silico leveraging pre-existing tumor transcriptomes...
Metastatic dissemination of breast cancer cells represents a significant clinical obstacle to curative therapy. The loss function metastasis suppressor genes is major rate-limiting step in progression that prevents the formation new colonies at distal sites. However, discovery using genomic efforts has been slow, potentially due their primary regulation by epigenetic mechanisms. Here, we report use model cell lines with same genetic lineage for identification novel gene, serum deprivation...
Basal-like breast cancer (BLBC) is an aggressive subtype of which often enriched with stem cells (CSC), but the underlying molecular basis for this connection remains elusive. We hypothesized that BLBC are able to establish a niche permissive maintenance CSCs and found tumor cell-derived periostin (POSTN), component extracellular matrix, as well corresponding cognate receptor, integrin α(v)β(3), highly expressed in subset cell lines CSC-enriched populations. Furthermore, we demonstrated...
Abstract Purpose: AZD8701 uses next-generation antisense oligonucleotide (ASO) technology to selectively reduce human forkhead box P3 (FOXP3) expression in regulatory T cells, reversing their immunosuppressive function. FOXP3 ASOs alone or with programmed cell death protein (ligand) 1 (PD-[L]1) inhibition attenuated tumor growth mice. We report a phase I study of combined durvalumab patients advanced solid tumors. Methods: Eligible had tumors and received prior standard-of-care treatment...
Cells sense and respond to the extracellular matrix (ECM) by way of integrin receptors, which facilitate cell adhesion intracellular signaling. Advances in understanding mammary epithelial hierarchy are converging with new developments that reveal how integrins regulate normal gland. But breast cancer, signaling contributes development progression tumors. This paper highlights recent studies examine role cells their malignant counterparts.
Abstract Background: GDF15 is overexpressed in solid tumors, with immunosuppressive effects on dendritic cells (DCs), T and myeloid-derived suppressor (MDSCs) the tumor microenvironment. AZD8853 an IgG1 monoclonal antibody that neutralizes GDF15. This Phase 1/2a, open-label study assessed monotherapy previously treated advanced/metastatic non-small-cell lung cancer, microsatellite-stable colorectal cancer (MSS-CRC) urothelial carcinoma (UC) (NCT05397171). Methods: Eligible pts were ≥18 years...
Deciphering molecular targets to enhance sensitivity chemotherapy is becoming a priority for effectively treating cancers. Loss of function mutations
Our previous studies showed that the depletion of outer kinetochore protein hBub1 upon activation spindle assembly checkpoint (SAC) primarily triggers early cell death mediated by p53 rather than aneuploidy. Here, we report phosphorylation at Ser37 is critical for proapoptotic activity SAC activation. Furthermore, show physically interacts with kinetochores in response to mitotic damage suggesting a direct role suppression death. This observation further substantiated inhibition...
It has been universally believed that spindle assembly checkpoint (SAC) proteins which include the kinetochore are involved in monitoring faithful segregation of sister chromatids during cell division and hence defects these result anueploidy. Furthermore, there multiple sources experimental data to suggest a defect p53 could also promote genomic instability leading Despite observations, molecular basis for prevention aneuploidy maintain integrity upon activation SAC largely remained...
Abstract Background: The cytokine GDF15 is overexpressed in solid malignant tumors such as colorectal, lung and urothelial cancer, where it modulates T cells, dendritic cells (DCs) myeloid-derived driving the tumor microenvironment toward an immunosuppressive, tumor-promoting state. AZD8853 a humanized immunoglobulin G1 monoclonal antibody that binds to, neutralizes, GDF15. Anti-GDF15 treatment increased cell proliferation DC activation, leading to antitumor immune response preclinical...
Abstract Recent evidence suggests that the molecular heterogeneity inherent to breast cancer, which underlies metastasis, resistance treatment and disease recurrence, can be driven by a distinct subpopulation of tumor cells referred as cancer stem (CSCs). However, extracellular cues intracellular pathways CSCs rely on remain unclear. Working with progression model system we found invasive cell line exhibit numerous stem-like characteristics. Gene expression profiling, along careful review...