A5023997044- DNA Repair Mechanisms
- Chromatin Remodeling and Cancer
- Acute Myeloid Leukemia Research
- Telomeres, Telomerase, and Senescence
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Nuclear Structure and Function
- Genomics and Chromatin Dynamics
- Hemoglobinopathies and Related Disorders
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Microplastics and Plastic Pollution
- Muscle Physiology and Disorders
- Education Systems and Policy
- Biochemical and Molecular Research
- Cancer Research and Treatments
- Virus-based gene therapy research
- Glioma Diagnosis and Treatment
- Viral Infectious Diseases and Gene Expression in Insects
- Chronic Myeloid Leukemia Treatments
- RNA Interference and Gene Delivery
- Skin Protection and Aging
University of Pennsylvania
2014-2024
Penn Center for AIDS Research
2020
Johns Hopkins University
2011-2019
Johns Hopkins Medicine
2019
Cancer Research Institute
2016
Sidney Kimmel Comprehensive Cancer Center
2014-2016
Cancer Research Institute of the Slovak Academy of Sciences
2015
University of Baltimore
2012-2013
Indiana University – Purdue University Indianapolis
2009
Indiana University School of Medicine
2009
Approximately 15% of cancers use homologous recombination for alternative lengthening telomeres (ALT). How the initiating genomic lesions invoke homology-directed telomere synthesis remains enigmatic. Here, we show that distinct dependencies exist in response to replication stress or DNA double-strand breaks (DSBs). RAD52 deficiency reduced spontaneous telomeric and stress-associated G2, concomitant with shortening damage. However, viability proliferation remained unaffected, suggesting...
A chemical dimerization approach is developed to induce phase separation of APB nuclear bodies involved in telomere elongation alternative lengthening telomeres (ALT) cancer cells. It reveals that ALT telomere-associated promyelocytic leukemia body (APB) fusion leads clustering provide templates for homology-directed synthesis, an ability decoupled from function enriching DNA repair factors.
DNA repair defects have been previously reported in myeloproliferative neoplasms (MPN). Inhibitors of PARP shown activity solid tumors with homologous recombination (HR). This study was performed to assess MPN sensitivity inhibitors ex vivoHR pathway integrity circulating myeloid cells evaluated by assessing the formation RAD51 foci after treatment ionizing radiation or inhibitors. Sensitivity erythroid and progenitors using colony assays.Six 14 primary samples had reduced exposure...
Defective homologous recombination (HR) has been reported in multiple myeloid disorders, suggesting a shared dysregulated pathway these diverse malignancies. Because targeting HR-defective cancers with PARP inhibition (PARPi) yielded clinical benefit, improved understanding of HR defects is needed to implement this treatment modality.We used an ex vivo irradiation-based assay evaluate repair, gene promoter methylation, and mRNA expression primary neoplastic cells. In vitro BRCA1 silencing...
Adeno-associated virus (AAV) vectors are promising tools for gene therapy. Currently, their potential is limited by difficulties in producing high vector yields with which to generate transgene protein product. AAV production depends part upon the replication (Rep) proteins required viral replication. We tested hypothesis that mutations start codon and upstream regulatory elements of Rep78/68 helper plasmids can regulate recombinant (rAAV) production. further whether resulting rAAV...
Abstract Telomerase-free cancer cells employ a recombination-based alternative lengthening of telomeres (ALT) pathway that depends on A LT-associated p romyelocytic leukemia (PML) nuclear b odies (APBs), whose function is unclear. We find APBs behave as liquid condensates, suggesting two potential mechanisms to promote telomere elongation: condensation enrich DNA repair factors for synthesis and coalescence cluster provide templates. Using chemically-induced dimerization, we show sumoylation...
Abstract Chronic myeloid neoplasms (CMNs) are characterized by excessive expansion of terminally differentiated blood cells arising from progenitors. This group hematologic clonal disorders includes the BCR-ABL1-negative myeloproliferative (MPNs), myelodysplastic syndromes (MDS) and MPN/MDS with features overlapping both subtypes. CMN patients at risk developing acute leukemia (AML), however curative therapy is lacking exception allogeneic stem cell transplant. Since leukemic transformation...
<p>Figure S1 shows the percentage of γH2AX- and RAD51- foci positive cells with without radiation.</p>
<p>Table S1 shows the primer sequences used for qMSP, MSP, RT-qPCR</p>
<p>Figure legends for Supplementary Fig S1, S2</p>
<p>Table S2 shows the BRCA1 qMSP results of samples assayed for HR status</p>
<p>Figure S2 shows the BRCA1 qMSP results and HR functional status of patient samples at multiple time points.</p>
<p>Table S1: Primers for Methylation Analysis. Figure Sensitivity of erythroid and myeloid progenitors to veliparib. S2: Reproducibility colony forming assays. S3: Veliparib IC50 as a function BRCA1 Promotor Methylation.</p>
<p>Figure S1 shows the percentage of γH2AX- and RAD51- foci positive cells with without radiation.</p>
<p>Figure S2 shows the BRCA1 qMSP results and HR functional status of patient samples at multiple time points.</p>
<p>Table S1 shows the primer sequences used for qMSP, MSP, RT-qPCR</p>