A5103262257- Cancer Genomics and Diagnostics
- Evolution and Genetic Dynamics
- Mathematical Biology Tumor Growth
- Malaria Research and Control
- Genetic Associations and Epidemiology
- Chronic Myeloid Leukemia Treatments
- Plant and animal studies
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Invertebrate Immune Response Mechanisms
- Gastric Cancer Management and Outcomes
- Evolutionary Game Theory and Cooperation
- Inflammatory Biomarkers in Disease Prognosis
- Mathematical and Theoretical Epidemiology and Ecology Models
- Esophageal Cancer Research and Treatment
- Ecology and Vegetation Dynamics Studies
- Radiomics and Machine Learning in Medical Imaging
- vaccines and immunoinformatics approaches
- 3D Printing in Biomedical Research
- HIV Research and Treatment
- Chemical Reactions and Isotopes
- Epigenetics and DNA Methylation
- Pharmacogenetics and Drug Metabolism
- Lung Cancer Treatments and Mutations
- Acute Myeloid Leukemia Research
- Genetic diversity and population structure
City, University of London
2020-2024
Gates Foundation
2024
Louisiana State University
2024
University of London
2021-2023
ETH Zurich
2019-2022
Université de Montpellier
2015-2021
Institut des Sciences de l'Evolution de Montpellier
2015-2021
University of Zurich
2019-2021
SIB Swiss Institute of Bioinformatics
2019-2020
Centre National de la Recherche Scientifique
2016-2017
Adaptive therapy is a dynamic cancer treatment protocol that updates (or ‘adapts’) decisions in anticipation of evolving tumor dynamics. This broad term encompasses many possible protocols patient-specific dose modulation or timing. maintains high levels burden to benefit from the competitive suppression treatment-sensitive subpopulations on treatment-resistant subpopulations. evolution-based approach has been integrated into several ongoing planned clinical trials, including metastatic...
Adaptive therapy (AT) aims to control tumour burden by maintaining therapy-sensitive cells exploit their competition with resistant cells. This relies on the assumption that have impaired cellular fitness. Here, using a model of resistance pharmacological cyclin-dependent kinase inhibitor (CDKi), we show this is valid when between spatially structured. We generate CDKi-resistant cancer and find they reduced proliferative fitness stably rewired cell cycle pathways. Low-dose CDKi outperforms...
Characterizing the mode-the way, manner or pattern-of evolution in tumours is important for clinical forecasting and optimizing cancer treatment. Sequencing studies have inferred various modes, including branching, punctuated neutral evolution, but it unclear why a particular pattern predominates any given tumour. Here we propose that tumour architecture key to explaining variety of observed genetic patterns. We examine this hypothesis using spatially explicit population genetics models...
Abstract The application of evolutionary and ecological principles to cancer prevention treatment, as well recognizing a selection force in nature, has gained impetus over the last 50 years. Following initial theoretical approaches that combined knowledge from interdisciplinary fields, it became clear using eco‐evolutionary framework is key importance understand cancer. We are now at pivotal point where accumulating evidence starts steer future directions discipline allows us underpin...
Evolutionary theory explains why metazoan species are largely protected against the negative fitness effects of cancers. Nevertheless, cancer is often observed at high incidence across a range species. Although there many challenges to quantifying epidemiology and assessing its causes, we claim that most modern-day in animals - humans particular due environments deviating from central tendencies distributions have prevailed during resistance evolution. Such novel environmental conditions may...
Peto's paradox is the lack of expected trend in cancer incidence as a function body size and lifespan across species. The leading hypothesis to explain this pattern natural selection for differential prevention larger, longer lived We evaluate whether similar effect exists within species, specifically humans. begin by reanalysing recently published dataset separate effects stem cell number replication rate, show that each has an independent on risk. When considering lifetime divisions...
Abstract Balance indices that quantify the symmetry of branching events and compactness trees are widely used to compare evolutionary processes or tree-generating algorithms. Yet, existing not defined for all rooted trees, unreliable comparing with different numbers leaves, sensitive presence absence rare types. The contributions this article twofold. First, we define a new class robust, universal tree balance indices. These take form similar Colless’ index but can account population sizes,...
Abstract Characterizing the mode – way, manner, or pattern of evolution in tumours is important for clinical forecasting and optimizing cancer treatment. DNA sequencing studies have inferred various modes, including branching, punctuated neutral evolution, but it unclear why a particular predominates any given tumour. 1, 2 Here we propose that differences tumour architecture alone can explain variety observed patterns. We examine this hypothesis using spatially explicit population genetic...
Antigenic variation in Plasmodium falciparum is regulated by transcriptional switches among members of the var gene family, each expressed a mutually exclusive manner and encoding different variant surface antigens collectively named PfEMP1. switching starts when first merozoites egress from liver begin their asexual proliferation within red blood cells. By erasing epigenetic memory we created parasites with no background, similar to that where expressed. Creating null-var background enabled...
Antigenic variation in the human malaria parasite Plasmodium falciparum involves sequential and mutually exclusive expression of members var multi-gene family appears to follow a non-random pattern. In this study, using detailed vitro gene transcription analysis culture-adapted HB3 strain P. falciparum, we show that antigenic switching is governed by global activation hierarchy favouring short highly diverse genes central chromosomal location. Longer more conserved genes, which have...
Increasing body of experimental evidence suggests that anticancer and antimicrobial therapies may themselves promote the acquisition drug resistance by increasing mutability. The successful control evolving populations requires such biological costs are identified, quantified included to evolutionarily informed treatment protocol. Here we identify, characterise exploit a trade-off between decreasing target population size generating surplus treatment-induced rescue mutations. We show...
Significance The evolution of cooperation is a central issue in biology and the social sciences. Study model systems microbes has focused on how “cooperators” “cheats” interact but rarely accounts for surrounding environment. We demonstrate environmental stress form antibiotics alters public goods bacterium. Antibiotics accentuate costs to cooperators, resulting their rapid demise relative cheats. In more applied vein, antibiotic resistance was maximal presence both producers cheats,...
Abstract Challenging the paradigm of maximum tolerated dose, recent studies have shown that a strategy aiming for containment, not elimination, can control tumor burden more effectively in vitro , mouse models, and clinic. These outcomes are consistent with hypothesis emergence resistance to cancer therapy may be prevented or delayed by exploiting competitive ecological interactions between drug-sensitive resistant cell subpopulations. However, although various mathematical computational...
Explaining the emergence and maintenance of intratumor heterogeneity is an important question in cancer biology. Tumor cells can generate considerable subclonal diversity, which influences tumor growth rate, treatment resistance, metastasis, yet we know remarkably little about how from different subclones interact. Here, confronted two murine mammary cell lines to determine both nature mechanisms cellular interactions vitro. Surprisingly, found that, compared monoculture, "winner" was...
Abstract Naked mole rats (NMRs) are subterranean eusocial mammals, known for their virtual absence of aging in first 20 to 30 years life, and apparent resistance cancer development. As such, this species has become an important biological model investigating the physiological molecular mechanisms behind resistance. Two recent studies have discovered middle late-aged worker (that is, non-breeding) NMRs captive populations exhibiting neoplasms, consistent with development, challenging claim...
Abstract The utility of intratumour heterogeneity as a prognostic biomarker is the subject ongoing clinical investigation. However, relationship between this marker and its impact mediated by an evolutionary process that not well understood. Here, we employ spatial computational model tumour evolution to assess when, why how can be used forecast growth rate progression‐free survival. We identify three conditions lead positive correlation clonal diversity subsequent rate: measured early in...
Many vector-borne pathogens rely on antigenic variation to prolong infections and increase their likelihood of onward transmission. This immune evasion strategy often involves mutually exclusive switching between members gene families that encode functionally similar but antigenically different variants during the course a single infection. Studies have suggested variant genes is non-random intrinsic probabilities being activated or silenced. These factors could create hierarchy expression...
The Euclidean solutions (instantons) discovered in field theories seem to be interpretable as tunnelings between vacuums with different winding numbers. associated transition rate for such has been estimated. We study the effect of temperature on quantum-field configurations thermodynamic equilibrium. do this by extending "most probable escape path" (MPEP) WKB vacuum-tunneling formalism Bitar and Chang finite temperatures. Our approach employs elementary results from quantum statistical...
Abstract The poor immunogenicity of pancreatic tumors makes them particularly difficult to treat. Standard chemotherapies and single agent immunotherapies have had notoriously little success in this arena. Oncolytic virus therapy has the potential enhance penetration immunotherapeutically-delivered CAR T cells into tumor improve treatment outcomes. We evaluate by combining two different mathematical approaches: an ordinary differential equation model simulate population level response...