A5045294037- Acute Lymphoblastic Leukemia research
- Cancer-related molecular mechanisms research
- CAR-T cell therapy research
- MicroRNA in disease regulation
- Acute Myeloid Leukemia Research
- Cancer Research and Treatments
- Circular RNAs in diseases
- Virus-based gene therapy research
- Mesenchymal stem cell research
- Glioma Diagnosis and Treatment
- RNA modifications and cancer
- Cancer Cells and Metastasis
- RNA Interference and Gene Delivery
- Cancer Mechanisms and Therapy
- Extracellular vesicles in disease
- Pluripotent Stem Cells Research
- Brain Metastases and Treatment
- Cancer Genomics and Diagnostics
- Microtubule and mitosis dynamics
- RNA Research and Splicing
- interferon and immune responses
- Cell death mechanisms and regulation
- Monoclonal and Polyclonal Antibodies Research
- Bioactive Compounds and Antitumor Agents
- Protein Degradation and Inhibitors
Brigham and Women's Hospital
2017-2025
Harvard University
2014-2025
University of South Carolina
2023-2024
Columbia University
2023-2024
Dana-Farber Cancer Institute
2021
Harvard Stem Cell Institute
2017-2021
St. Mary's Medical Center
2019
Harbor–UCLA Medical Center
2019
Khyber Teaching Hospital
2019
Massachusetts General Hospital
2012-2018
Abstract Glioblastoma (GBM) is a highly aggressive brain cancer characterized by local invasion and angiogenic recruitment, yet metastatic dissemination extremely rare. Here, we adapted microfluidic device to deplete hematopoietic cells from blood specimens of patients with GBM, uncovering evidence circulating tumor (CTC). Staining scoring criteria for GBM CTCs were first established using orthotopic patient-derived xenografts (PDX), then applied clinically: identified in at least one...
Proteins are densely packed in cells and tissues, where they form complex nanostructures. Expansion microscopy (ExM) variants have been used to separate proteins from each other preserved biospecimens, improving antibody access epitopes. Here, we present an ExM variant, decrowding expansion pathology (dExPath), that can expand away human brain specimens, including formalin-fixed paraffin-embedded (FFPE) clinical specimens. Immunostaining of dExPath-expanded specimens reveals, with nanoscale...
Abstract Therapeutically engineered stem cells (SC) are emerging as an effective tumor-targeted approach for different cancer types. However, the assessment of long-term fate therapeutic SC post-tumor treatment is critical if such promising therapies to be translated into clinical practice. In this study, we have developed efficient SC-based strategy that simultaneously allows killing tumor and eradication after highly malignant glioblastoma multiforme (GBM). Mesenchymal (MSC) co-express...
The deregulation of the epidermal growth factor receptor (EGFR) has a significant role in progression tumors. Despite development number EGFR-targeting agents that can arrest tumor growth, their success clinic is limited several types, particularly highly malignant glioblastoma multiforme (GBM). In this study, we generated and characterized EGFR-specific nanobodies (ENb) imageable proapoptotic ENb immunoconjugates released from stem cells (SC) to ultimately develop unique EGFR-targeted...
Tumor-propagating cells (TPCs) share self-renewal properties with normal stem and drive continued tumor growth. However, mechanisms regulating TPC are largely unknown, especially in embryonal rhabdomyosarcoma (ERMS)-a common pediatric cancer of muscle. Here, we used a zebrafish transgenic model ERMS to identify role for intracellular NOTCH1 (ICN1) increasing TPCs by 23-fold. ICN1 expanded enabling the de-differentiation into self-renewing myf5+ TPCs, breaking rigid differentiation...
Abstract T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes. Using a transgenic screen in zebrafish, thymocyte selection–associated high mobility group box protein (TOX) was uncovered as collaborating oncogenic driver that accelerated T-ALL onset by expanding the initiating pool transformed clones and elevating genomic instability. TOX highly expressed majority human required for proliferation continued xenograft growth mice. wide array functional analyses,...
Abstract The coronavirus disease 2019 (COVID-19) pandemic has grown to be a global public health crisis with no safe and effective treatments available yet. Recent findings suggest that severe acute respiratory syndrome 2 (SARS-CoV-2), the pathogen causes COVID-19, could elicit cytokine storm drives edema, dysfunction of airway exchange, distress in lung, followed by cardiac injury thromboembolic events leading multiorgan failure death. Mesenchymal stem cells (MSCs), owing their powerful...
Astrocyte elevated gene-1 (AEG-1) is a key contributor to hepatocellular carcinoma (HCC) development and progression. To enhance our understanding of the role AEG-1 in hepatocarcinogenesis, transgenic mouse with hepatocyte-specific expression (Alb/AEG1) was developed. Treating Alb/AEG-1, but not wild-type (WT) mice, N-nitrosodiethylamine resulted multinodular HCC steatotic features associated modulation genes regulating invasion, metastasis, angiogenesis, fatty acid synthesis. Hepatocytes...
Three type-1 repeat (3TSR) domain of thrombospondin-1 is known to have anti-angiogenic effects by targeting tumor-associated endothelial cells, but its effect on tumor cells unknown. This study explored the potential 3TSR target glioblastoma (GBM) in vitro and vivo. We show that upregulates death receptor (DR) 4/5 expression a CD36-dependent manner primes resistant GBMs necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced caspase-8/3/7 mediated apoptosis. engineered human...
CRISPR-engineered receptor-specific self-targeted tumor cells demonstrate antitumor efficacy in vitro and vivo.
Only a subset of cancer patients inoculated with oncolytic herpes simplex virus (oHSV) type-1 has shown objective response in phase 1 and 2 clinical trials. This raised speculations whether resistance tumor cells to oHSV therapy may be limiting factor. In this study, we have identified established patient derived primary glioblastoma multiforme (GBM) stem cell lines (GSC) resistant also necrosis factor-related apoptosis-inducing ligand (TRAIL) that recently promise preclinical initial...
Abstract Retinoid X receptor (RXR) regulates key cellular responses such as cell growth and development, this regulation is frequently perturbed in various malignancies, including hepatocellular carcinoma (HCC). However, the molecule(s) that physically govern deregulation are mostly unknown. Here, we identified RXR an interacting partner of astrocyte-elevated gene-1 (AEG-1)/metadherin (MTDH), oncogene upregulated all cancers. Upon interaction, AEG-1 profoundly inhibited RXR/retinoic acid...
Abstract Dysregulation of miRNA expression has been implicated in cancer. Numerous strategies have explored to modulate miR but sub-optimal delivery and inability concurrently target multiple pathways involved tumor progression limited their efficacy. In this study, we the potential co-modulation upregulated miR-21 downregulated miR-7 enhance therapeutic outcomes heterogenic types. We first engineered lentiviral (LV) adeno-associated viral (AAV) vectors that preferentially express anti-sense...
Abstract Developing therapeutics that target multiple receptor signaling pathways in tumors is critical as therapies targeting single specific biomarker/pathway have shown limited efficacy patients with cancer. In this study, we extensively characterized a bi-functional molecule comprising of epidermal growth factor (EGFR) targeted nanobody (ENb) and death (DR) ligand TRAIL (ENb-TRAIL). We show ENb-TRAIL has therapeutic tumor cells from different cancer types which do not respond to either...
MicroRNAs (miRs) are known to play a pivotal role in tumorigenesis, controlling cell proliferation and apoptosis. In this study, we investigated the potential of miR-7 prime resistant tumor cells apoptosis glioblastoma (GBM).
Cellular therapies offer a promising therapeutic strategy for the highly malignant brain tumor, glioblastoma (GBM). However, their clinical translation is limited by lack of effective target identification and stringent testing in pre-clinical models that replicate standard treatment GBM patients. In this study, we show detection cell surface death receptor (DR) on CD146-enriched circulating tumor cells (CTC) captured from blood mice bearing patients diagnosed with GBM. Next, developed...