A5031757228- Hematopoietic Stem Cell Transplantation
- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immune cells in cancer
- T-cell and B-cell Immunology
- Mesenchymal stem cell research
- Chronic Myeloid Leukemia Treatments
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Digital Imaging for Blood Diseases
- Cell Image Analysis Techniques
- Microfluidic and Bio-sensing Technologies
- Fractional Differential Equations Solutions
- Diffusion and Search Dynamics
- Multiple Myeloma Research and Treatments
- AI in cancer detection
- Acute Lymphoblastic Leukemia research
- Radiomics and Machine Learning in Medical Imaging
- Platelet Disorders and Treatments
- Hematological disorders and diagnostics
- Immune Cell Function and Interaction
Imperial College London
2015-2023
The Francis Crick Institute
2023
University of Bradford
2013
Bone marrow vascular niches sustain hematopoietic stem cells (HSCs) and are drastically remodeled in leukemia to support pathological functions. Acute myeloid (AML) produce angiogenic factors, which likely contribute this remodeling, but anti-angiogenic therapies do not improve AML patient outcomes. Using intravital microscopy, we found that progression leads differential remodeling of vasculature central endosteal bone regions. Endosteal pro-inflammatory cytokines gradually degrade...
Abstract Aging facilitates the expansion of hematopoietic stem cells (HSCs) carrying clonal hematopoiesis-related somatic mutations and development myeloid malignancies, such as myeloproliferative neoplasms (MPNs). While cooperating can cause transformation, it is unclear whether distinct bone marrow (BM) HSC-niches influence growth therapy response HSCs same oncogenic driver. Here we found different BM niches for in MPN subtypes. JAK–STAT signaling differentially regulates CDC42-dependent...
A key predictor for the success of gene-modified T cell therapies cancer is persistence transferred cells in patient. The propensity less differentiated memory to expand and survive efficiently has therefore made them attractive candidates clinical application. We hypothesized that redirecting specialized niches BM support differentiation would confer increased therapeutic efficacy. show overexpression chemokine receptor CXCR4 CD8+ (TCXCR4) enhanced their migration toward vascular-associated...
Measuring three-dimensional (3D) localization of hematopoietic stem cells (HSCs) within the bone marrow microenvironment using intravital microscopy is a rapidly expanding research theme. This approach holds key to understanding detail HSC-niche interactions, which are critical for appropriate cell function. Due complex tissue architecture and progressive introduction scattering signal loss at increasing imaging depths, there no ready-made software handle efficient segmentation unbiased...
Abstract The hematopoietic stem cell (HSC) niche provides essential microenvironmental cues for the production and maintenance of HSCs within bone marrow. During inflammation, dynamics are perturbed, but it is not known whether changes to HSC–niche interaction occur as a result. We visualize directly in vivo, enabling detailed analysis 3D migration patterns murine marrow following Trichinella spiralis infection. Spatial statistical these HSC trajectories reveals two distinct modes behavior:...
Multi-potent progenitor (MPP) cells act as a key intermediary step between haematopoietic stem and the entirety of mature blood cell system. Their eventual fate determination is thought to be achieved through migration in out spatially distinct niches. Here we first analyze statistically MPP trajectory data obtained from series long time-course 3D vivo imaging experiments on irradiated mouse calvaria, report that MPPs display transient super-diffusion with apparent non-Gaussian displacement...
Blood vessels inside the bone marrow (BM) play a vital role in maintenance of hematopoietic stem cell (HSCs). Investigating interaction HSCs relative to vasculature has become main headline for many recent studies. Advances microscopy and image analysis using mouse models have allowed detection, identification automated quantification alongside their vascular niche. This resulted new hypotheses concerning activation state adjacent different blood vessel types (for example sinusoids vs....
The manual monitoring process of cancer cells development is a subjective, time consuming process, as it typically relies on the visual recognition and experience level pathologists. An automated nuclei segmentation quantification in Immunohistologically stained images have remained challenging task. Previous methods used shown an oversight counting two different types within same image (i.e. positive brown negative blue nuclei). Our exclusive method addresses this issue by producing means...
Abstract Aging facilitates the expansion of hematopoietic stem cells (HSCs) carrying clonal hematopoiesis (CH)-related somatic mutations and development myeloid malignancies, such as myeloproliferative neoplasms (MPNs). While cooperating can cause transformation, it remains unclear whether distinct bone marrow (BM) HSC niches influence growth therapy response HSCs same pathogenic driver. Here we found different BM for in MPN subtypes. JAK-STAT signaling differentially regulates...
Abstract The haematopoietic stem cell (HSC) niche provides essential micro-environmental cues for the production and maintenance of HSCs within bone marrow. During inflammation, dynamics are perturbed, but it is not known whether changes to HSC-niche interaction occur as a result. We visualise directly in vivo, enabling detailed analysis 3D migration patterns murine marrow following Trichinella spiralis infection. Spatial statistical these HSC trajectories reveals two distinct modes...
Abstract Acute Myeloid Leukemia, a hematological malignancy with poor clinical outcome, is composed of hierarchically heterogeneous cells. We examine the contribution this heterogeneity to disease progression in context anti-tumor immune responses and investigate whether these regulate balance between stemness differentiation AML. Combining phenotypic analysis proliferation dynamics fate-mapping AML cells murine model, we demonstrate presence terminally differentiated, chemoresistant...
Multi-potent progenitor (MPP) cells act as a key intermediary step between haematopoietic stem and the entirety of mature blood cell system. Their eventual fate determination is thought to be achieved through migration in out spatially distinct niches. Here we first analyze statistically MPP trajectory data obtained from series long time-course 3D in-vivo imaging experiments on irradiated mouse calvaria, report that MPPs display transient super-diffusion with apparent non-Gaussian...