A5083819739- Mathematical Biology Tumor Growth
- Evolution and Genetic Dynamics
- Evolutionary Game Theory and Cooperation
- Cancer, Hypoxia, and Metabolism
- Mathematical and Theoretical Epidemiology and Ecology Models
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Cancer Cells and Metastasis
- Immune cells in cancer
- Ecosystem dynamics and resilience
- Gene Regulatory Network Analysis
- Angiogenesis and VEGF in Cancer
- Monoclonal and Polyclonal Antibodies Research
- Cancer Genomics and Diagnostics
- Bioinformatics and Genomic Networks
- Computational Drug Discovery Methods
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Protein purification and stability
- Statistical Methods in Clinical Trials
- Complex Systems and Time Series Analysis
- Statistical Mechanics and Entropy
- Gastric Cancer Management and Outcomes
- Blood properties and coagulation
- Erythrocyte Function and Pathophysiology
EMD Group (United States)
2025
Ono Pharmaceutical (United States)
2018-2025
Merck (Germany)
2023-2024
Northeastern University
2022-2024
Merck Serono (Italy)
2023-2024
Arizona State University
2012-2022
Merck & Co., Inc., Rahway, NJ, USA (United States)
2018-2021
Tufts Medical Center
2014-2016
Tufts Children's Hospital
2014-2016
Tufts University
2013-2014
That tumors cause changes in surrounding tissues is well documented, but whether they also affect distant uncertain. Such knowledge may be important understanding the relationship between cancer and overall patient health. To address this question, we examined to sites of implanted for genomic damage using cohorts C57BL/6 BALB/c mice with early-stage subcutaneous syngeneic grafts, specifically, B16 melanoma, MO5076 sarcoma, COLON26 carcinoma. Here report that levels two serious types DNA...
The role of the immune system in tumor elimination has been shown to be increasingly ambiguous, as many tumors not only escape recognition by adaptive response but also even prime cells promote growth. This effect is achieved through a number mechanisms, which include both direct interference with and indirect immunosuppression modification microenvironment. We propose that upregulation glycolysis consequent lowering pH microenvironment, can take advantage control system, already exploited...
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...
Tumor-immune interactions are often framed as predator-prey. This imperfect analogy describes how immune cells (the predators) hunt and kill immunogenic tumor prey). It allows for evaluation of cell populations that change over time during immunoediting it also considers the system changes in response to these alterations. However, two aspects predator-prey type models not typically observed immuno-oncology. The first concerns conversion prey killed into predator biomass. In standard models,...
Mathematical modeling has made significant contributions to drug design, development, and optimization. Virtual clinical trials that integrate mathematical models explore patient heterogeneity its impact on a variety of therapeutic questions have recently risen in popularity. Here, we outline best practices for creating virtual patients from ultimately implement execute trial. In this practical guide, discuss provide examples model parameter estimation, sensitivity, identifiability, cohort...
In 2008, Pienta et al. (Transl Oncol. 2008;1:158–164) introduced the term ecological therapy for cancer treatment and, in particular, emphasized that destruction of tumor microenvironment would be more effective than just killing cells inhabit it. Proposed here is an expansion on idea cancer, incorporating 1) literature species invasion, i.e., a right cancerous clone needs to at place time actually invade its environment, and 2) niche construction, is, once formed, they modify their (niche...
Both normal wound healing and tumor angiogenesis are mitigated by the sequential, carefully orchestrated release of growth stimulators inhibitors. These regulators released from platelet clots formed at sites activated endothelium in a temporally spatially controlled manner, order their depends on affinity to glycosaminoglycans (GAG) such as heparan sulfate (HS) within extracellular matrix, open canallicular system. The formation vessel sprouts, triggered regulating factors with lowest...
Metronomic chemotherapy can drastically enhance immunogenic tumor cell death. However, the responsible mechanisms are still incompletely understood. Here, we develop a mathematical model to elucidate underlying complex interactions between growth, immune system activation, and therapy-mediated Our is conceptually simple, yet it provides surprisingly excellent fit empirical data obtained from GL261 mouse glioma treated with cyclophosphamide on metronomic schedule. The includes terms...
Refining dose projections requires a deep understanding of drug-target relationships at the site action, which is often challenging to achieve. Here we present case study how one can refine for TIGIT-targeted immunotherapy by leveraging information from well-studied PD-1 pathway since co-expression and TIGIT on immune cells provides unique opportunity extrapolate data target inform dosing strategy other. We develop fit-for-purpose mathematical model that captures experimentally observed...
<title>Abstract</title> The emerging recognition of multiple states T cell exhaustion, which only some are targetable by checkpoint inhibitors, has provided new insights into the variability in patient responses to immunotherapy. We hypothesized that non-responders therapy have a higher proportion non-targetable, terminally exhausted cells compared responders. To investigate this, we analyzed single-cell RNA sequencing data from 27 patients with head and neck squamous carcinoma (HNSCC)...
Bispecific T Cell Engagers (BTC) constitute an exciting antibody design in immuno-oncology that acts to bypass antigen presentation and forms a direct link between cancer immune cells the tumor microenvironment (TME). By design, BTCs are efficacious only when drug is bound both cell targets, therefore approaches maximize drug-target trimer TME should drug's efficacy. In this study, we quantitatively investigate how concentration of ternary complex its distribution depend on targets' specific...
Cancer therapies often fail when intolerable toxicity or drug-resistant cancer cells undermine otherwise effective treatment strategies. Over the past decade, adaptive therapy has emerged as a promising approach to postpone emergence of resistance by altering dose timing based on tumor burden thresholds. Despite encouraging results, these protocols overlook crucial role toxicity-induced breaks, which may permit regrowth. Herein, we explore following question: would incorporating feedback...
As tumors outgrow their blood supply and become oxygen deprived, they switch to less energetically efficient but oxygen-independent anaerobic glucose metabolism. However, cancer cells maintain glycolytic phenotype even in the areas of ample (Warburg effect). It has been hypothesized that competitive advantage get over aerobic is achieved through secretion lactic acid, which a by-product glycolysis. creates acidic microenvironment around tumor can be toxic normal somatic cells. This...
An overview of a general approach for mathematical modeling evolving heterogeneous populations using wide class selection systems and replicator equations (RE) is presented. The method allows visualizing evolutionary trajectories over time, while still enabling use analytical tools bifurcation theory. developed theory involves introducing escort auxiliary "keystone" variables, which reduce complex multi-dimensional inhomogeneous models to low dimensional ODEs that in many cases can be...
Despite the revolutionary impact of immune checkpoint inhibition on cancer therapy, lack response in a subset patients, as well emergence resistance, remain significant challenges. Here we explore theoretical consequences existence multiple states cell exhaustion to therapy. In particular, consider emerging understanding that T cells can exist various states: fully functioning cytotoxic cells, reversibly exhausted with minimal cytotoxicity, and terminally cells. We hypothesize inflammation...