A5091392935- Mathematical Biology Tumor Growth
- Evolution and Genetic Dynamics
- Gene Regulatory Network Analysis
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Mathematical and Theoretical Epidemiology and Ecology Models
- Neutropenia and Cancer Infections
- CAR-T cell therapy research
- Hepatitis C virus research
- Numerical methods for differential equations
- Virus-based gene therapy research
- Quantum Mechanics and Non-Hermitian Physics
- Fractional Differential Equations Solutions
- Viral Infectious Diseases and Gene Expression in Insects
- Nonlinear Waves and Solitons
- Blood disorders and treatments
- HIV/AIDS Research and Interventions
- Hepatitis B Virus Studies
- Computational Drug Discovery Methods
- Cancer Immunotherapy and Biomarkers
- COVID-19 Clinical Research Studies
- Immune Response and Inflammation
- SARS-CoV-2 and COVID-19 Research
- Phagocytosis and Immune Regulation
- demographic modeling and climate adaptation
University of Leeds
2023-2025
Pfizer (United States)
2024
Los Alamos National Laboratory
2020-2022
McGill University
2017-2021
University of Alberta
2015-2017
Abstract Human immunodeficiency virus (HIV)-1-specific broadly neutralizing monoclonal antibodies are currently under development to treat and prevent HIV-1 infection. We performed a single-center, randomized, double-blind, dose-escalation, placebo-controlled trial of single administration the V3-glycan-specific antibody PGT121 at 3, 10 30 mg kg –1 in HIV-uninfected adults HIV-infected on antiretroviral therapy (ART), as well multicenter, open-label one infusion viremic not ART (no....
Oncolytic virotherapies, including the modified herpes simplex virus talimogene laherparepvec (T-VEC), have shown great promise as potent instigators of anti-tumour immune effects. The OPTiM trial, in particular, demonstrated superior anti-cancer effects T-VEC compared to systemic immunotherapy treatment using exogenous administration granulocyte-macrophage colony-stimulating factor (GM-CSF). Theoretically, a combined approach leveraging cytokine and oncolytic virotherapy would elicit an...
Background Immunotherapies, driven by immune-mediated antitumorigenicity, offer the potential for significant improvements to treatment of multiple cancer types. Identifying therapeutic strategies that bolster antitumor immunity while limiting immune suppression is critical selecting combinations and schedules durable benefits. Combination oncolytic virus (OV) therapy, wherein complementary OVs are administered in succession, such promise, yet their translation from preclinical studies...
Considerable effort has been made to better understand why some people suffer from severe COVID-19 while others remain asymptomatic. This led important clinical findings; with generally experience persistently high levels of inflammation, slower viral load decay, display a dysregulated type-I interferon response, have less active natural killer cells and increased neutrophil extracellular traps. How these findings are connected the pathogenesis remains unclear. We propose mathematical model...
Chronic hepatitis B virus (HBV) infection is strongly associated with increased risk of liver cancer and cirrhosis. While existing treatments effectively inhibit the HBV life cycle, viral rebound frequently occurs following treatment interruption. Consequently, functional cure rates chronic remain low there interest in a novel modality, capsid assembly modulators (CAMs). Here, we develop multiscale mathematical model CAM infection. By fitting to participant data from phase I trial...
Intra-tumour heterogeneity is a leading cause of treatment failure and disease progression in cancer. While genetic mutations have long been accepted as primary mechanism generating this heterogeneity, the role phenotypic plasticity becoming increasingly apparent driver intra-tumour heterogeneity. Consequently, understanding resistance key component improving cancer therapy. We develop mathematical model stochastic phenotype switching that tracks evolution drug-sensitive drug-tolerant...
Estimating model parameters is a crucial step in mathematical modelling and typically involves minimizing the disagreement between predictions experimental data. This calibration data can change throughout study, particularly if performed simultaneously with experiments, or during an on-going public health crisis as case of COVID-19 pandemic. Consequently, optimal parameter set, maximal likelihood estimator (MLE), function set. Here, we develop numerical technique to predict evolution MLE We...
PGT121 is a broadly neutralizing antibody in clinical development for the treatment and prevention of HIV-1 infection via passive administration. targets V3-glycan demonstrated potent antiviral activity phase I trial. Resistance to monotherapy rapidly occurred majority participants this trial with sampled rebound viruses being entirely resistant mediated neutralization. However, two individuals experienced long-term ART-free viral suppression following infusion retained sensitivity upon...
We develop and analyse a mathematical model of tumour-immune interaction that explicitly incorporates heterogeneity in tumour cell cycle duration by using distributed delay differential equation. derive necessary sufficient condition for local stability the cancer-free equilibrium which amount completely characterizes disease progression. Consistent with immunoediting hypothesis, we show decreasing leads to expansion. Finally, simulating model, strength determines long-term success or...
We use the McKendrick equation with variable ageing rate and randomly distributed maturation time to derive a state dependent delay differential equation. show that resulting preserves non-negativity of initial conditions we characterise local stability equilibria. By specifying distribution age, recover discrete, uniform gamma equations. how reduce case system discrete equations ordinary To illustrate benefits these reductions, convert previously published transit compartment models into equivalent
Chronic hepatitis B virus (HBV) infection is strongly associated with increased risk of liver cancer and cirrhosis. While existing treatments effectively inhibit the HBV life cycle, viral rebound occurs rapidly following treatment interruption. Consequently, functional cure rates chronic remain low there interest in a novel modality, capsid assembly modulators (CAMs). Here, we develop multiscale mathematical model CAM infection. By fitting to participant data from phase I trial...
Phenotypic adaptation, the ability of cells to change phenotype in response external pressures, has been identified as a driver drug resistance cancer. To quantify phenotypic adaptation BRAFV600E-mutant melanoma, we develop theoretical model that emerges from data analysis WM239A-BRAFV600E cell growth rates challenge with BRAF-inhibitor encorafenib. Our constitutes population which each is individually described by one multiple discrete and plastic states are directly linked drug-dependent...
Understanding what shapes the latent human immunodeficiency virus type 1 (HIV-1) reservoir is critical for developing strategies cure. We measured frequency of persistent HIV-1 infection after 5 years suppressive antiretroviral therapy initiated during chronic infection. Pretreatment CD8+ T-cell activation, nadir CD4 count, and CD4:CD8 ratio predicted size.
Compartmental ordinary differential equation (ODE) models are used extensively in mathematical biology. When transit between compartments occurs at a constant rate, the well-known linear chain trick can be to show that ODE model is equivalent an Erlang distributed delay (DDE). Here, we demonstrate compartmental with non-linear rates and possibly delayed arguments also scalar equation. To illustrate utility of these equivalences, calculate equilibria DDE, compute characteristic function--...
Abstract We develop and analyse a mathematical model of tumour-immune interaction that explicitly incorporates heterogeneity in tumour cell cycle duration by using distributed delay differential equation. Our necessary sufficient conditions for local stability the cancer free equilibrium completely characterise importance disease progression. Consistent with immunoediting hypothesis, we show decreasing leads to expansion. Finally, immune involvement is crucial determining long-term response...
Intratumour phenotypic heterogeneity is nowadays understood to play a critical role in disease progression and treatment failure. Accordingly, there has been increasing interest the development of mathematical models capable capturing its cancer cell adaptation. This can be systematically achieved by means comprising phenotype-structured nonlocal partial differential equations, tracking evolution density distribution population, which may compared gene protein expression distributions...
Abstract Adaptive resistance contributes significantly to treatment failure in many cancers. Despite the increased prevalence of experimental studies that interrogate this phenomenon, there remains a lack applicable quantitative tools characterise data, and importantly distinguish between as discrete phenotype (potentially heterogeneous) continuous distribution phenotypes. To address this, we develop stochastic individual-based model adaptive low-cell-count proliferation assays. That our...
Delayed processes are ubiquitous throughout biology. These delays may arise through maturation or as the result of complex multi-step networks, and mathematical models with distributed increasingly used to capture heterogeneity present in these delayed processes. Typically, delay differential equations simulated by discretizing using existing tools for resulting multi-delay an equivalent representation under additional assumptions on process. Here, we use framework functional continuous...
Abstract In drug development, quantitative systems pharmacology (QSP) models are becoming an increasingly important mathematical tool for understanding response variability and generating predictions to inform development decisions. Virtual populations essential sampling uncertainty potential in QSP model predictions, but many clinical efficacy endpoints can be difficult capture with that typically rely on mechanistic biomarkers. oncology, challenges particularly significant when connecting...
Abstract Intra-tumour heterogeneity is a leading cause of treatment failure and disease progression in cancer. While genetic mutations have long been accepted as primary mechanism generating this heterogeneity, the role phenotypic plasticity becoming increasingly apparent driver intra-tumour heterogeneity. Consequently, understanding resistance key component improving cancer therapy. We develop mathematical model stochastic phenotype switching that tracks evolution drug-sensitive...
Gamma distributed delay differential equations (DDEs) arise naturally in many modelling applications. However, appropriate numerical methods for generic gamma DDEs have not previously been implemented. Modellers therefore resorted to approximating the distribution with an Erlang and using linear chain technique derive equivalent system of ordinary (ODEs). In this work, we address lack tools two ways. First, develop a functional continuous Runge-Kutta (FCRK) method numerically integrate DDE...
Abstract In spite of the recent focus on development novel targeted drugs to treat cancer, cytotoxic chemotherapy remains standard treatment for vast majority patients. Unfortunately, is associated with high hematopoietic toxicity that may limit its efficacy. We have previously established potential strategies mitigate chemotherapy-induced neutropenia (a lack circulating neutrophils) using a mechanistic model granulopoiesis predict interactions defining neutrophil response and define optimal...