Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 26 for “"Clonal Dynamics"”.
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Clonal dynamics of haematopoiesis across the human lifespan
… or blood loss; and increased risk of clonal haematopoiesis and blood cancers. The cellular alterations that underpin these age-related phenotypes, which typically manifest in individuals aged over 70, remain elusive. In my thesis I have aimed to investigate whether changes in HSC …
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Clonal Dynamics in Barrett's Oesophagus and Oesophageal Adenocarcinoma
… well studied for IM, little is known about the clonal dynamics in GM and OAC. Clonal dynamics can be explored through longitudinal or multi-sample genomic studies, or experimentally. There is no physiologically relevant in vivo model for BO/OAC, but patient derived 3D organoids may provide an …
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Inferring Clonal Dynamics in Blood using Single-Cell Measurements
… follow their progeny over time to ask whether clonally related cells in myeloproliferative neoplasms (MPNs) favor particular blood cell fates. Myeloproliferative neoplasms are clonal disorders driven most frequently by the JAK2-V617F mutation, which arises in a single hematopoietic stem cell …
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Illuminating Clonal Dynamics: Development and Use of a High-Throughput Cellular Barcoding System to Track Clonal Evolution
It is increasingly recognized that tracking the clonal dynamics of large populations is important in understanding aspects of cancer and stem cell biology. Attempts to track the contributions of individual cells to the clonality of large homogenous populations, however, have been constrained by …
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Somatic Mutation Detection in Leukemia-Derived Circulating DNA: Utility in Monitoring Clonal Dynamics and Disease Response in Pediatric Acute Lymphoblastic Leukemia
… studying of genetic heterogeneity and tracking clonal dynamics throughout therapy. Here, we employ targeted Next-Generation Sequencing (NGS) using a specifically designed ALL custom gene panel for Ct-DNA analysis of sequential plasma samples of 14 pediatric ALL during remission induction …
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Somatic evolution in human blood and colon
… cancer occur in normal cells, and the normal clonal dynamics of the tissue determine a mutant cell’s ability to establish a malignant clone; yet these remain poorly understood in humans. One tissue was selected for the exploration of each of these two facets of somatic evolution: blood for …
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Stem and Progenitor Cells in Homeostatic Maintenance and Perturbation of the Pulmonary Epithelium
… process are poorly understood at the level of clonal resolution. Secretory cells are known progenitor cells of the pseudostratified airway epithelium, however their clonal dynamics in homeostasis are unknown. Here, I elucidate their contribution to homeostasis, and reveal they are more …
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Decoding The Evolutionary Response to Prostate Cancer Therapy Using Plasma Genome Sequencing
… patients with 2–5 serial plasma samples revealed clonal dynamics and genome evolution in response to hormonal and chemotherapy. By performing an integrated evolutionary analysis, minor subclones were identified in 9 patients that expanded in response to therapy and harbored mutations associated …
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Somatic Mutation in Cancer and Healthy Human Tissue
… to investigate the lineage relationships and clonal dynamics within prostatic ductal structures. Through combination of genetic and morphological relationship between the epithelial microdissections, long-ranging developmental clones could be detected throughout the ductal structures. A …
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Clonal Phenotype Mapping Reveals Genomic Alterations Underlying Tumor Immunosuppression during Immunotherapy
… immune interactions. Using orthotopic clonal replica tumors, we tracked clonal dynamics in response to anti-PD1 therapy and found that while treatment had limited impact on overall tumor volume, it induced profound shifts in clonal composition. Spatial lineage analysis of …
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EVALUATION OF THE RISK OF SECONDARY LEUKEMIAS IN CANCER SURVIVORS
… Chemotherapy may also play a role in increasing clonal hematopoiesis (CH), a clinical entity associated with a higher risk of developing hematological malignancies. Moreover, the presence of germline mutations in cancer predisposing genes can increase the risk of t-MNs. Our hypothesis is that …
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PROBABILISTIC AND DEEP LEARNING APPROACHES TO MODELING BIOLOGICAL SYSTEMS
… a model-based clustering approach for subclonal deconvolution. By introducing a probabilistic hierarchical structure, this method accounts for observational noise, for shared uncertainty across karyotypes, and allows inference on a substantially bigger proportion of the genome. I then …
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Barcoding tools to track development and function of stem cell constructs for biomedicine
… processes including complex cellular growth dynamics, patterns of gene expression and clonal expansion of cells drives regeneration and analogously, biological tissue development. Improved understanding of developmental biology can thus improve the function and persistence of regenerative …
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Somatic Mutations in Primary Sjögren’s Syndrome
… The results illustrate the mutational trends and clonal dynamics present in immune cells and glandular epithelial cells, suggesting ways in which somatic mutations in key cell types may be affecting disease pathogenesis. To complement the genomic studies and interrogate the lymphocyte cell types …
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The natural history of clonal haematopoiesis
… throughout life, some of which can drive clonal expansion. Such expansions are frequent in the haematopoietic system of healthy individuals and have been termed clonal haematopoiesis (CH). While CH predisposes to myeloid neoplasia and other diseases, we have limited understanding of its …
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Clonal deconvolution of transcriptomic signatures and their spatial organisation in a mouse model of breast cancer
… in which cancer cells diverge and form clonal populations with distinct phenotypic, genetic, or epigenetic states within the same tumour. This intrinsic heterogeneity provides a fuel for cancer evolution enabling tumour cell populations to adapt to selective pressures imposed by the …
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Selection and competition of somatic mutations in normal epithelia
… affects cancer development. The nature of mutant clonal growth and competition in normal epidermis has been a subject of debate. A study found that mutant clone sizes inferred from DNA sequencing of normal human eyelid skin were consistent with a mathematical model of neutral cell dynamics, …
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Prevalence and fate of pro-oncogenic clones in the human colon
… seemed necessary to induce biases in clonal dynamics but not sufficient to explain the different fates of clones in terms of their ANC. In addition, larger KRAS patches seemed to possess different characteristics from smaller ones, often exhibiting abnormal crypt morphology and …
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Notch activation and clone fate in intestinal homeostasis and inflammation
… of the effect Notch signals play on ISC dynamics during homeostasis and a disease setting, with most studies focussed on the small intestinal epithelium rather than the colon. In this study I aim to determine the effect of Notch signals on the cell cycle and ISC clone dynamics in the …
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Longitudinal Clonal Lineage Dynamics and Functional Characterization of Pancreatic Cancer Chemo-Resistance and Metastasization
… By dissecting tumors and characterizing clonal lineages, we are better understanding the intricacies of tumor evolution. Tumors are represented by the presence of and dynamic interactions amongst clonal lineages. Each lineage and each cell contributes to tumor dynamics through intrinsic …
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