John H. Lockhart

ORCID: 0000-0002-2727-6969
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About
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Research Areas
  • RNA modifications and cancer
  • MicroRNA in disease regulation
  • Pregnancy and preeclampsia studies
  • Cancer-related molecular mechanisms research
  • RNA Interference and Gene Delivery
  • Radiomics and Machine Learning in Medical Imaging
  • Geological Modeling and Analysis
  • Advanced biosensing and bioanalysis techniques
  • Medical Image Segmentation Techniques
  • Mitochondrial Function and Pathology
  • AI in cancer detection
  • Augmented Reality Applications
  • Single-cell and spatial transcriptomics
  • Cancer Immunotherapy and Biomarkers
  • Genetic Syndromes and Imprinting
  • interferon and immune responses
  • Virus-based gene therapy research
  • CAR-T cell therapy research
  • Lung Cancer Research Studies
  • Ubiquitin and proteasome pathways
  • Vascular Malformations Diagnosis and Treatment
  • Cancer therapeutics and mechanisms
  • Computational Drug Discovery Methods
  • Immunotherapy and Immune Responses
  • Pluripotent Stem Cells Research

Moffitt Cancer Center
2020-2025

Molecular Oncology (United States)
2021-2024

University of South Florida
2015-2023

Preeclampsia (PE) is a common cause of maternal morbidity, characterized by impaired trophoblast invasion and spiral artery transformation resulting in progressive uteroplacental hypoxia. Given the primary role LIN28A LIN28B modulating cell metabolism, differentiation, invasion, we hypothesized that and/or regulates differentiation its dysregulation may contribute to PE. Here show expressed ∼1300-fold higher than human term placenta predominant paralog cultures. The expression mRNA protein...

10.1096/fj.201801163r article EN The FASEB Journal 2018-10-11

During implantation, cytotrophoblasts undergo epithelial-to-mesenchymal transition (EMT) as they differentiate into invasive extravillous trophoblasts (EVTs). The primate-specific microRNA cluster on chromosome 19 (C19MC) is exclusively expressed in the placenta, embryonic stem cells and certain cancers however, its role EMT gene regulation unknown. In situ hybridization for miR-517a/c, a C19MC cistron microRNA, first trimester human placentas displayed strong expression villous gradual...

10.1038/s41598-020-59812-8 article EN cc-by Scientific Reports 2020-02-20

Cardiovascular disease is the leading cause of death and disability worldwide. Effective delivery cell-selective therapies that target atherosclerotic plaques neointimal growth while sparing endothelium remains Achilles heel percutaneous interventions. The current study utilizes synthetic microRNA switch therapy self-assembles to form a compacted, nuclease-resistant nanoparticle <200 nM in size when mixed with cationic amphipathic cell-penetrating peptide (p5RHH). These nanoparticles possess...

10.1016/j.ymthe.2021.01.032 article EN cc-by-nc-nd Molecular Therapy 2021-02-05

Lung adenocarcinoma (LUAD), the most common histological subtype of lung cancer( 1, 2 ), is a disease elderly, with an average age diagnosis about 70 years age( 3 ). Older associated increased incidence KRAS-driven LUAD( 4 particularly deadly type LUAD characterized by treatment resistance and relapse. Despite this, our understanding how old shapes evolution remains incomplete. While age-related increase in cancer risk was previously ascribed to accumulation mutations over time, we are now...

10.1101/2025.01.20.633951 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2025-01-24

mRNA therapeutics hold great promise for the treatment of human diseases. While incorporating naturally occurring modified nucleotides during synthesis has greatly increased their potency and safety, challenges in selective expression have hindered clinical applications. MicroRNA (miRNA)-regulated vitro-transcribed mRNAs, called miRNA switches, been used to control exogenous a cell-selective manner. However, effect nucleotide modifications on miRNA-dependent silencing not examined. Here we...

10.1016/j.omtn.2018.12.007 article EN cc-by-nc-nd Molecular Therapy — Nucleic Acids 2018-12-18

Objective— Infantile hemangiomas (IHs) are the most common benign vascular neoplasms of infancy, characterized by a rapid growth phase followed spontaneous involution, or triggered propranolol treatment poorly understood mechanisms. LIN28/let-7 axis plays central role in regulation stem cell self-renewal and tumorigenesis. However, LIN28B/let-7 signaling IH pathogenesis has not yet been elucidated. Approach Results— LIN28B is highly expressed proliferative less involuted propranolol-treated...

10.1161/atvbaha.118.310908 article EN Arteriosclerosis Thrombosis and Vascular Biology 2018-05-03

Abstract Summary The heterogeneous cell types of the tumor-immune microenvironment (TIME) play key roles in determining cancer progression, metastasis and response to treatment. We report development TIMEx, a novel TIME deconvolution method emphasizing on estimating infiltrating immune cells for bulk transcriptomics using pan-cancer single-cell RNA-seq signatures. also implemented comprehensive, user-friendly web-portal users evaluate TIMEx other methods with transcriptomic profiles....

10.1093/bioinformatics/btab244 article EN Bioinformatics 2021-04-14

Abstract Preclinical genetically engineered mouse models (GEMMs) of lung adenocarcinoma are invaluable for investigating molecular drivers tumor formation, progression, and therapeutic resistance. However, histological analysis these GEMMs requires significant time training to ensure accuracy consistency. To achieve a more objective standardized analysis, we used machine learning create GLASS-AI, image tool that the broader cancer research community can utilize grade, segment, analyze tumors...

10.1038/s41698-023-00419-3 article EN cc-by npj Precision Oncology 2023-07-18

As one of the most widespread metabolic diseases, atherosclerosis affects nearly everyone as they age; arteries gradually narrow from plaque accumulation over time reducing oxygenated blood flow to central and periphery causing heart disease, stroke, kidney problems, even pulmonary disease. Personalized medicine promises bring treatments based on individual genome sequencing that precisely target molecular pathways underlying its symptoms, but date only a few genotypes have been identified....

10.3390/jpm9020021 article EN Journal of Personalized Medicine 2019-04-29

<h3>Background</h3> The Chromosome 19 MicroRNA Cluster (C19MC) is a group of 46 microRNAs that span approximately 100 Kb the human genome. C19MC exclusively expressed in placenta, regulating trophoblast migration and acting as an antiviral mechanism, but can become overexpressed cancers.<sup>1</sup> Additionally, has been hypothesized to suppress maternal immunity protect developing fetus.<sup>2</sup> We hypothesize cancer cells overexpress exploit this function evade anti-tumor immunity....

10.1136/jitc-2024-sitc2024.0887 article EN cc-by-nc Regular and Young Investigator Award Abstracts 2024-11-01

Chromosome-19 miRNA cluster (C19MC) restricts viruses depending on the multinucleated-state of placental trophoblasts. However, relationship C19MC to multinucleation is unknown. Here we show that, overexpressed in multiple cancer-subsets, with meiosis-related gene-signatures. We discover a novel meiosis-III parallel progression meiotic-nuclear division (MND) and cytokinesis where, C19MC-miRNAs promote meiotic-bridged-chromosomes (MBC) delay MND generate multinucleated cells. starts...

10.2139/ssrn.4735962 preprint EN 2024-01-01

The chromosome-19 miRNA cluster (C19MC) restricts viruses depending on the multinucleated state of placental trophoblasts. However, relationship C19MC to multinucleation is unknown. Here we show that coexpressed in multiple cancer type subsets with meiosis-related genes. We discovered a novel meiosis-III exhibits simultaneous progression meiotic nuclear division (MND) and cytokinesis. promotes bridged-chromosomes block MND cytokinesis generate cells. starts invagination membrane form...

10.1016/j.isci.2024.111132 article EN cc-by-nc-nd iScience 2024-10-10

Abstract Breast cancer (BC) is the most diagnosed and second leading cancer-related cause of mortality among women in US. Despite advances treatment, BC remains a challenge due to its metastatic potential. The aggressive subtype, triple negative (TN), often harbors mutations tumor suppressor gene, p53. One effects mutant p53 involves inhibition suppressive functions TAp63, family member. Loss TAp63 leads formation mammary adenocarcinomas mice, part through regulation group nine long...

10.1158/1538-8514.rnadrivers24-b013 article EN Molecular Cancer Therapeutics 2024-11-14

Abstract Preclinical mouse models of lung adenocarcinoma are invaluable for the discovery molecular drivers tumor formation, progression, and therapeutic resistance. Histological analyses these preclinical require significant investments time training to ensure accuracy consistency. Analysis by a clinical pathologist is gold standard in this approach, but may be difficult obtain due cost availability their services. As an alternative we have developed digital pathology tool identify,...

10.1158/1557-3265.adi21-po-082 article EN Clinical Cancer Research 2021-03-01

Abstract P53 is frequently mutated in a wide variety of tumors; yet, the regulation and expression downstream targets during tumor progression response to therapy unknown. Here, we use Kras/p53-driven lung adenocarcinoma mouse as model system identify p53-driven molecular signatures that predict progression. Using these tumors, have developed digital pathology tool using machine learning grade adenocarcinomas. To do this, analyzed hematoxylin eosin (H&amp;E) from models with Kras...

10.1158/1538-7445.tumhet2020-po-023 article EN Cancer Research 2020-11-01
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