A5014860176- Prostate Cancer Treatment and Research
- Nanoplatforms for cancer theranostics
- 3D Printing in Biomedical Research
- Estrogen and related hormone effects
- Cell Adhesion Molecules Research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Nanoparticle-Based Drug Delivery
- RNA modifications and cancer
- Glioma Diagnosis and Treatment
- Cancer Cells and Metastasis
- Ubiquitin and proteasome pathways
- Cancer Research and Treatments
- Cellular Mechanics and Interactions
- Single-cell and spatial transcriptomics
- Advanced Fluorescence Microscopy Techniques
- Advanced Breast Cancer Therapies
- Cancer Genomics and Diagnostics
- Microtubule and mitosis dynamics
- Optical Coherence Tomography Applications
- Cancer Mechanisms and Therapy
- Cell Image Analysis Techniques
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related Molecular Pathways
- Protein Degradation and Inhibitors
- Advanced Biosensing Techniques and Applications
Brigham and Women's Hospital
2001-2025
Harvard University
2018-2024
Massachusetts Institute of Technology
2014-2022
Woman's Hospital
2022
Broad Institute
2019
Allen Institute
2016-2017
Dana-Farber Cancer Institute
2017
Koch Institute for Integrative Cancer Research At MIT
2015-2016
Leipzig University
2011
Fraunhofer Society
2010
In model systems, bacteria present in human pancreatic tumors confer resistance to the anticancer drug gemcitabine.
Fibronectin (FN) is a major component of the tumor microenvironment, but its role in promoting metastasis incompletely understood. Here, we show that FN gradients elicit directional movement breast cancer cells, vitro and vivo Haptotaxis on requires direct interaction between α5β1 integrin MENA, an actin regulator, involves increases focal complex signaling cell-mediated extracellular matrix (ECM) remodeling. Compared with higher levels prometastatic MENA(INV) isoform associate α5, which...
An implantable microdevice is demonstrated to release microdoses of multiple drugs into confined regions tumors and allows for assessment each drug’s efficacy identify optimal therapy.
Extrinsic signals are implicated in breast cancer resistance to HER2-targeted tyrosine kinase inhibitors (TKIs). To examine how microenvironmental influence resistance, we monitored TKI-treated cell lines grown on microenvironment microarrays composed of printed extracellular matrix proteins supplemented with soluble proteins. We tested ∼2,500 combinations 56 and 46 basal-like HER2+ (HER2E) or luminal-like (L-HER2+) cells treated the TKIs lapatinib neratinib. In HER2E cells, hepatocyte...
ABSTRACT Background Prostate cancer (PCa) treatment often involves systemic therapies with varying mechanisms of action, affecting individuals differently. Implantable microdevices (IMDs) are designed to test multiple drugs within a patient's tumor, but the feasibility MRI‐guided placement in PCa has not been evaluated. Purpose To provide proof concept for placing IMDs into lesions MRI guidance predict patient‐specific responses therapies. Study Type Prospective. Population Fifteen...
Abstract Systematically identifying synergistic combinations of targeted agents and immunotherapies for cancer treatments remains difficult. In this study, we integrated high-throughput high-content techniques—an implantable microdevice to administer multiple drugs into different sites in tumors at nanodoses multiplexed imaging tumor microenvironmental states—to investigate the cell immunological response signatures treatment regimens. Using a mouse model breast cancer, identified effective...
Identifying therapeutic targets in rare cancers remains challenging due to the paucity of established models perform preclinical studies. As a proof-of-concept, we developed patient-derived cancer cell line, CLF-PED-015-T, from paediatric patient with undifferentiated sarcoma. Here, confirm that this line recapitulates histology and harbours majority somatic genetic alterations found metastatic lesion isolated at first relapse. We then pooled CRISPR-Cas9 RNAi loss-of-function screens...
Clinically available BH3 mimetic drugs targeting BCLXL and/or BCL2 (navitoclax and venetoclax, respectively) are effective in some hematologic malignancies, but have limited efficacy solid tumors. This study aimed to identify combination therapies that exploit clinical mimetics for prostate cancer.
Identifying the properties that distinguish invasive cells from noninvasive is of prime interest in understanding metastasis formation during cancer. We have taken pairs five organ types, each consisting a highly cell line and its counterpart, characterized their active passive biomechanical assays mimic mechanical perturbations likely experienced by vivo metastasizing tumor cells. Our setup applies compressive pressure to entire cellvia flat SFM cantilever while directly measuring cell's...
Medulloblastoma is the most common childhood malignant brain tumor.The lethal medulloblastoma subtype exhibits a high expression of GABA A receptor α5 subunit gene and MYC amplification.New benzodiazepines have been synthesized to function as α5-GABA ligands, but these had undesirable side effects in nude mouse xenograft model system (4).To compare their efficacy with that standard-of-care treatments, we employed newly developed microscale implantable device allows for high-throughput...
Abstract We hypothesized that candidate dependencies for which there are small molecules either approved or in advanced development a nononcology indication may represent potential therapeutic targets. To test this hypothesis, we performed genome-scale loss-of-function screens hundreds of cancer cell lines. found knockout EGLN1, encodes prolyl hydroxylase domain-containing protein 2 (PHD2), reduced the proliferation subset clear ovarian lines vitro. EGLN1-dependent cells exhibited...
Taxane therapy remains the standard of care for triple-negative breast cancer. However, high frequencies recurrence and progression in treated patients indicate that metastatic cancer cells can acquire resistance to this drug. The actin regulatory protein MENA particularly its invasive isoform, MENAINV, are established drivers metastasis. MENAINV expression is significantly correlated with metastasis poor outcome human We investigated whether isoforms might play a role driving...
Significance Mutagenic translesion synthesis (TLS) increases cell survival after DNA damage by bypassing lesions that normally block replication but introduces mutations. In cancer cells, REV1/POLζ-dependent mutagenic TLS can contribute to intrinsic chemoresistance, while the mutations it underlie acquired chemoresistance. Interfering with this pathway genetically or small molecule inhibitor JH-RE-06 has been shown improve cisplatin chemotherapy suppressing tumor growth and enhancing in...
The lack of reliable predictive biomarkers to guide effective therapy is a major obstacle the advancement for high-grade gliomas, particularly glioblastoma (GBM), one few cancers whose prognosis has not improved over past several decades. With this pilot clinical trial (number NCT04135807), we provide first-in-human evidence that drug-releasing intratumoral microdevices (IMDs) can be safely and effectively used obtain patient-specific, high-throughput molecular histopathological drug...
Abstract Glioblastoma (GBM) is the most aggressive and treatment-resistant primary brain tumor. Despite advancements in immunotherapies targeted therapies, patient outcomes remain poor due to complexity of GBM tumor microenvironment. The spatial heterogeneity within tumors leads variable immune responses drug efficacy, posing significant challenges for effective treatment. This study presents an innovative approach using implantable microdevices (IMDs) localized delivery real-time monitoring...
Abstract The selection of optimal therapies for patients with ovarian cancer is difficult, especially in recurrent disease. An implantable microdevice (IMD) a new technology to evaluate situ drug responses cancer. IMD, about the size grain rice, implanted into human or murine solid tumors and releases microdoses up 20 compounds spatially distinct regions tumor. Histologic analysis tissue surrounding IMD used quantitate tumor response. Using IMDs, we can measure sensitivity multiple drugs...
There is an unmet need for new antimitotic drug combinations that target cancer-specific vulnerabilities. Based on our finding of elevated biomolecule oxidation in mitotically arrested cancer cells, we combined Plk1 inhibitors with TH588, MTH1 inhibitor prevents detoxification oxidized nucleotide triphosphates. This combination showed robust synergistic killing cancer, but not normal, cells that, surprisingly, was MTH1-independent. To dissect the underlying mechanism, developed VISAGE, a...
Bismuth telluride has garnered considerable attention owing to its versatile properties applicable in thermoelectric and antibacterial domains, as well intriguing topological insulating properties. In this work, our group fabricated bismuth thin films with various ratios using radio frequency magnetron sputtering. The surface of these were thoroughly analyzed by employing a diverse array analytical techniques, including X-ray photoelectron spectroscopy (XPS), ultraviolet (UPS), scanning...
Activating mutations involving the PI3K pathway occur frequently in human cancers. However, inhibitors primarily induce cell cycle arrest, leaving a significant reservoir of tumor cells that may acquire or exhibit resistance. We searched for genes are required survival mutant cancer presence inhibition by conducting genome scale shRNA-based apoptosis screen PIK3CA breast cell. identified 5 (PIM2, ZAK, TACC1, ZFR, ZNF565) whose suppression induced death upon inhibition. showed small molecule...
Abstract Determining how forces are produced by and propagated through the cytoskeleton (CSK) of cell is great interest as dynamic processes CSK intimately correlated with many molecular signaling pathways. We presenting a novel approach for integrating measurements on elasticity, transcellular force propagation, cellular generation to obtain comprehensive description mechanical properties under loading. This uses combination scanning microscopy (SFM) Total Internal Reflection Fluorescence...
Abstract Purpose: Treatment of BRAF-mutated melanoma tumors with BRAF inhibitor–based therapy produces high response rates, but limited duration in the vast majority patients. Published investigations resistance mechanisms suggest numerous examples tumor adaptation and signal transduction bypass mechanisms, without insight into biomarkers that would predict which mechanism will predominate. Monitoring phenotypic multiple adaptive simultaneously within same as it adapts during treatment has...