A5024863178- Cancer Genomics and Diagnostics
- Mathematical Biology Tumor Growth
- Evolution and Genetic Dynamics
- Sarcoma Diagnosis and Treatment
- Radiomics and Machine Learning in Medical Imaging
- Advanced Radiotherapy Techniques
- Lung Cancer Treatments and Mutations
- Cancer Cells and Metastasis
- Glioma Diagnosis and Treatment
- Gene Regulatory Network Analysis
- Bioinformatics and Genomic Networks
- Head and Neck Cancer Studies
- Acute Myeloid Leukemia Research
- Vascular Tumors and Angiosarcomas
- Evolutionary Game Theory and Cooperation
- Microtubule and mitosis dynamics
- Cancer-related molecular mechanisms research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Surgical site infection prevention
- Lung Cancer Diagnosis and Treatment
- RNA modifications and cancer
- Mathematical and Theoretical Epidemiology and Ecology Models
- RNA Research and Splicing
- Protein Degradation and Inhibitors
- Medical Imaging Techniques and Applications
Cleveland Clinic
2016-2025
Cleveland Clinic Lerner College of Medicine
2019-2025
Cancer Institute (WIA)
2018-2025
Rush University Medical Center
2025
Case Western Reserve University
2008-2024
University School
2017-2024
University Hospitals Cleveland Medical Center
2024
Case Comprehensive Cancer Center
2021-2024
University of Cambridge
2024
Riverside Methodist Hospital
2023
Abstract Antibiotic resistance represents a growing health crisis that necessitates the immediate discovery of novel treatment strategies. One such strategy is identification collateral sensitivities, wherein evolution under first drug induces susceptibility to second. Here, we report sequential regimens derived from in vitro experiments may have overstated therapeutic benefit, predicting collaterally sensitive response where cross-resistance ultimately occurs. We quantify likelihood this...
The increasing rate of antibiotic resistance and slowing discovery novel treatments presents a growing threat to public health. Here, we consider simple model evolution in asexually reproducing populations which considers adaptation as biased random walk on fitness landscape. This associates the global properties landscape with algebraic Markov chain transition matrix allows us derive general results non-commutativity irreversibility natural selection well cycling strategies. Using this...
Whole brain radiotherapy (WBRT) is a mainstay of treatment in patients with both identifiable metastases and prophylaxis for microscopic disease. The use WBRT has decreased somewhat recent years due to advances radiation technology, allowing more localized delivery radiation, growing concerns regarding the late toxicity profile associated WBRT. This prompted development several ongoing prospective studies designed provide Level I evidence guide optimal approaches intracranial metastases. In...
microRNAs are key regulators of the human transcriptome across a number diverse biological processes, such as development, aging and cancer, where particular miRNAs have been identified tumour suppressive oncogenic. In this work, we elucidate, in comprehensive manner, 15 epithelial cancer types comprising 7316 clinical samples from Cancer Genome Atlas, association miRNA expression target regulation with phenotypic hallmarks cancer. Utilising penalised regression techniques to integrate...
Abstract BACKGROUND: The most‐used prognostic scheme for malignant gliomas included only patients aged 18 to 70 years. purpose of this study was develop a model ≥70 years age with newly diagnosed glioblastoma. METHODS: A total 437 glioblastoma, pooled from 2 tertiary academic institutions, identified recursive partitioning analysis (RPA). resulting model, based on the final pruned RPA tree, validated using 265 glioblastoma data set independently compiled by French consortium. RESULTS:...
Abstract Genomic instability and high mutation rates cause cancer to acquire numerous mutations chromosomal alterations during its somatic evolution; most are termed passengers because they do not confer phenotypes. Evolutionary simulations genomic studies suggest that mildly deleterious accumulate can collectively slow progression. Clinical data also an association between passenger load response therapeutics, yet no causal link the effects of progression has been established. To assess...
ABSTRACT Despite high initial efficacy, targeted therapies eventually fail in advanced cancers, as tumors develop resistance and relapse. In contrast to the substantial body of research on molecular mechanisms resistance, understanding how evolves remains limited. Using an experimental model ALK positive NSCLC, we explored evolution different clinical inhibitors. We found that can originate from heterogeneous, weakly resistant subpopulations with variable sensitivity Instead commonly assumed...
Drug resistance remains an elusive problem in cancer therapy, particularly for novel targeted therapies. Much work is focused upon the development of arsenal therapies, towards oncogenic driver genes such as ALK-EML4, to overcome inevitable that develops over time. Currently, after failure first line ALK TKI another administered, though collateral sensitivity not considered. To address this, we evolved rearranged non-small cell lung (H3122) a panel 4 TKIs, and performed analysis. All...
Personal protective equipment (PPE) is crucially important to the safety of both patients and medical personnel, particularly in event an infectious pandemic. As incidence Coronavirus Disease 2019 (COVID-19) increases exponentially United States many parts world, healthcare provider demand for these necessities currently outpacing supply. In midst current pandemic, there has been a concerted effort identify viable ways conserve PPE, including decontamination after use. this study, we outline...
In this study, we experimentally measure the frequency-dependent interactions between a gefitinib-resistant non–small cell lung cancer population and its sensitive ancestor via evolutionary game assay. We show that cost of resistance is insufficient to accurately predict competitive exclusion growth rate measurements are required. Using data, then gefitinib treatment results in ancestor, while absence likely, but not guaranteed, resistant strain. Then, using simulations, demonstrate...
Antimicrobial resistance was estimated to be associated with 4.95 million deaths worldwide in 2019. It is possible frame the antimicrobial problem as a feedback-control problem. If we could optimize this and translate our findings clinic, slow, prevent, or reverse development of high-level drug resistance. Prior work on topic has relied systems where exact dynamics parameters were known priori. In study, extend using reinforcement learning (RL) approach capable effective cycling policies...
Glioblastomas with a specific mutation in the isocitrate dehydrogenase 1 (IDH1) gene have better prognosis than gliomas wild-type IDH1. Here we compare IDH1 mutational status 172 contrast-enhancing glioma patients invasion profile generated by patient-specific mathematical model developed based on MR imaging. We show that IDH1-mutated were relatively more invasive for all as well subset of 158 histologically confirmed glioblastomas. The appearance this increased, model-predicted appears to...
Abstract Many tumors are hierarchically organized and driven by a subpopulation of tumor-initiating cells (TIC), or cancer stem cells. TICs uniquely capable recapitulating the tumor thought to be highly resistant radio- chemotherapy. Macroscopic patterns expansion before treatment regression during tied dynamics TICs. Until now, quantitative information about fraction from macroscopic burden trajectories could not inferred. In this study, we generated method based on mathematical model that...
ABSTRACT DISCLAIMER This article does not represent the official recommendation of Cleveland Clinic or Case Western Reserve University School Medicine, nor has it yet been peer reviewed. We are releasing early, pre-peer review, to allow for quick dissemination/vetting by scientific/clinical community given necessity rapid conservation personal protective equipment (PPE) during this dire global situation. welcome feedback from community. Personal (PPE), including face shields, surgical masks,...