A5034895796- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Virus-based gene therapy research
- Cancer Immunotherapy and Biomarkers
- Fetal and Pediatric Neurological Disorders
- Neurogenesis and neuroplasticity mechanisms
- Advanced Electron Microscopy Techniques and Applications
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- Barrier Structure and Function Studies
- Phagocytosis and Immune Regulation
- Mesenchymal stem cell research
- Signaling Pathways in Disease
- Immune cells in cancer
- Nuclear Receptors and Signaling
- RNA regulation and disease
- Brain Metastases and Treatment
- MicroRNA in disease regulation
- Neuroinflammation and Neurodegeneration Mechanisms
- Long-Term Effects of COVID-19
- Hematopoietic Stem Cell Transplantation
- Acute Lymphoblastic Leukemia research
- Craniofacial Disorders and Treatments
- Genetics and Neurodevelopmental Disorders
Brigham and Women's Hospital
2020-2025
Harvard University
2020-2025
Harvard Stem Cell Institute
2021-2024
The University of Queensland
2017-2021
Queensland Eye Institute
2021
University of Malaya
2012-2014
The administration of inactivated tumor cells is known to induce a potent antitumor immune response; however, the efficacy such an approach limited by its inability kill before inducing responses. Unlike cells, living have ability track and target tumors. Here, we developed bifunctional whole cancer cell–based therapeutic with direct killing immunostimulatory roles. We repurposed from interferon-β (IFN-β) sensitive resistant using CRISPR-Cas9 knocking out IFN-β–specific receptor subsequently...
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...
Glioblastoma (GBM) is the most aggressive and common type of malignant brain tumor diagnosed in adults. Preclinical immunocompetent mouse models generated using cells play a pivotal role testing therapeutic efficacy emerging immune-based therapies for GBMs. However, clinical translatability such studies limited as lines do not fully recapitulate GBMs seen inpatient settings. In this study, we three distinct, imageable human-GBM (hGBM) humanized mice patient-derived GBM that cover phenotypic...
Increasing accumulation and retention of nanomedicines within tumor tissue is a significant challenge, particularly in the case brain tumors where access to through vasculature restricted by blood-brain barrier (BBB). This makes application neuro-oncology often considered unfeasible, with efficacy limited regions disease progression compromised BBB. However, little understood about how evolving tumor-brain physiology during affects permeability designer nanomedicines. We report here...
Abstract Background Immune-checkpoint inhibitors have shown clinical benefit in non-small cell lung cancer (NSCLC) derived brain metastasis (BM), however, their efficacy to leptomeningeal (LLBM) remains poor. Methods A paired matched RNA expression dataset of patients with NSCLCs and BMs was analyzed idenfiy BM specific suppressive tumor microenvironment (TME) features. Next, we created immune-competent LLBM mouse models that mimic LLBM. We evaluated the intrathecal (IT) delivery allogeneic...
Significance Germ-line mutation in the tumor suppressor TP53 causes Li–Fraumeni syndrome (LFS), a complex predisposition to multiple cancers. Types of cancers and ages at diagnosis vary among subjects families, with apparent genetic anticipation: i.e., earlier cancer onset successive generations. It has been proposed that anticipation is caused by accumulation copy-number variations (CNV) context haploinsufficiency. Using genome/exome sequencing, we found no evidence increased rates CNVs two...
The nuclear factor I (NFI) family of transcription factors plays an important role in the development cerebral cortex humans and mice. Disruption IA (NFIA), IB (NFIB), or IX (NFIX) results abnormal corpus callosum, lateral ventricles, hippocampus. However, expression function these genes has not been examined detail adult brain, cell type-specific NFIA, NFIB, NFIX is currently unknown. Here, we demonstrate that each NFI protein shows a distinct laminar pattern mouse neocortex their differs...
Encapsulated cell-based therapies for solid tumors have shown promising results in pre-clinical settings. However, the inability to culture encapsulated therapeutic cells prior their transplantation has limited translation into clinical In this study, we created a wide variety of engineered (ThC) loaded micropore-forming gelatin methacryloyl (GelMA) hydrogel (CellDex) capsules that can be cultured vitro surgically debulked tumors. We show both allogeneic and autologous cells, such as stem...
Oncolytic virus therapy has shown activity against primary melanomas; however, its efficacy in brain metastases remains challenging, mainly because of the delivery and immunosuppressive nature tumors brain. To address this challenge, we first established PTEN-deficient melanoma metastasis mouse models characterized them to be more compared with melanoma, mimicking clinical settings. Next, developed an allogeneic twin stem cell (TSC) system composed two tumor-targeting (SC) populations. One...
Corpus callosum dysgenesis (CCD) is a congenital disorder that incorporates either partial or complete absence of the largest cerebral commissure. Remodelling interhemispheric fissure (IHF) provides substrate for callosal axons to cross between hemispheres, and its failure main cause CCD. However, it unclear whether defects in this process could give rise heterogeneity expressivity phenotypes seen human cases We identify incomplete IHF remodelling as key structural correlate range...
Choong SS, Latiff ZA, Mohamed M, Lim LLW, Chen KS, Vengidasan L, Razali H, Abdul Rahman EJ, Ariffin H for Malaysian Society of Paediatric Haematology‐Oncology. Childhood adrenal cortical carcinoma as a sentinel cancer detecting families with germline TP53 mutations. Li‐Fraumeni syndrome (LFS) is highly penetrant, autosomal dominant disorder where affected individuals carry 50% risk developing before 30 years age. It most commonly associated mutations in the tumour suppressor gene, ....
Recent progress in cancer cell-based therapies has led to effective targeting and robust immune responses against cancer. However, the inherent safety risks of using live cells necessitate creation an optimized switch without hindering efficacy immunotherapy. The existing switches typically induce tolerogenic cell death, potentially leading immunosuppressive tumor microenvironment (TIME), which is counterproductive goals Here, we developed characterized inducible RIPK3-driven necroptotic...
Nuclear factor one (NFI) transcription factors are implicated in both brain development and cancer mice humans play an essential role glial differentiation. NFI expression is reduced human astrocytoma samples, particularly those of higher grade, whereas over-expression protein can induce the differentiation glioblastoma cells within tumour xenografts cell lines vitro. These data indicate that proteins may act as suppressors glioma. To test this hypothesis, we generated complex mouse genetic...
A 6-week-old female infant presented with pallor, hepatosplenomegaly and a leucocyte count of 329 9 10/l (91% blasts). Light microscopy the peripheral blood film showed blasts rounded nuclei scanty cytoplasm. No intracytoplasmic vacuoles were present (top left). Immunophenotyping by flow cytometry using (bottom panels) expression CD10, surface membrane immunoglobulin (mu heavy chain kappa light chain) no nuclear terminal deoxynucleotidyl transferase or CD34, indicating mature B-cell...
Abstract Leptomeningeal metastasis (LM) is one of the severe disease conditions in brain (BM) and results poor prognosis reduction quality life. Immunotherapies such as anti-Programmed cell Death (PD)-1 antibodies have shown improved overall survival against non-small lung cancer (NSCLC).. However, clinical benefit patients with NSCLC derived LM still limited due to penetration therapeutic agents into cerebrospinal fluid (CSF) lack understanding tumor microenvironment LM. In this study, we...
Abstract The nuclear factor one (NFI) transcription factors play key roles in regulating the onset of both neuronal and glial differentiation during cortical development. Reduced NFI expression results delayed differentiation, which is associated with neurodevelopmental disorders humans that include intellectual disability, agenesis corpus callosum macrocephaly. Despite their importance, our understanding how individual family members are regulated development remains limited. Here, we...
Abstract Corpus callosum dysgenesis (CCD) is a congenital disorder that incorporates either partial or complete absence of the largest cerebral commissure. Remodelling interhemispheric fissure (IHF) provides substrate for callosal axons to cross between hemispheres, and its failure main cause CCD. However, it unclear whether defects in this process could give rise heterogeneity expressivity phenotypes seen human cases We identify incomplete IHF remodelling as key structural correlate range...
Abstract The administration of inactivated tumor cell lysate is known to induce a potent antitumor immune response, however, their therapeutic efficacy as shown in Phase I-III clinical trials limited. This could be attributed the lack direct cytotoxic effect on cells and inability trigger strong response. Unlike cells, living possess unique potential home self-target tumors. Therefore, repurposing cells’ self-homing property natural source neoantigens advantageous for self-targeted cancer...
Abstract The nuclear factor I (NFI) family of transcription factors plays an important role in the development cerebral cortex humans and mice. Disruption IA (NFIA), IB (NFIB), or IX (NFIX) results abnormal corpus callosum, lateral ventricles, hippocampus. However, expression function these genes has not been examined detail adult brain, cell type‐specific NFIA, NFIB, NFIX is currently unknown. Here, we demonstrate that each NFI protein shows a distinct laminar pattern mouse neocortex their...
Abstract Astrocytomas are composed of heterogeneous cell populations. Compared to grade IV glioblastoma, low-grade astrocytomas have more differentiated cells and associated with a better prognosis. Therefore, inducing cellular differentiation may serve as therapeutic strategy. The nuclear factor one (NFI) transcription factors essential for normal astrocytic therefore could be effectors in glioblastoma. We analysed expression family members NFIA NFIB using high-grade astrocytoma mRNA...