- RNA Research and Splicing
- RNA regulation and disease
- Acute Myeloid Leukemia Research
- Viral Infections and Immunology Research
- CRISPR and Genetic Engineering
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- Cancer Risks and Factors
- Lung Cancer Treatments and Mutations
- Inflammatory Biomarkers in Disease Prognosis
- Lung Cancer Diagnosis and Treatment
- Metastasis and carcinoma case studies
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- interferon and immune responses
- Nutrition and Health in Aging
- Chronic Myeloid Leukemia Treatments
- Retinoids in leukemia and cellular processes
- Tracheal and airway disorders
- Telomeres, Telomerase, and Senescence
- Eosinophilic Disorders and Syndromes
- Chronic Lymphocytic Leukemia Research
Sanford Consortium for Regenerative Medicine
2019-2023
University of California, San Diego
2018-2023
La Jolla Alcohol Research
2020
Highlights•A-to-I RNA editing alters cell-cycle transit by impairing pri-miR-26a maturation•Enforced miR-26a expression reduces BC CML progenitor propagation in vivo•pri-miR-155 downregulation ADAR1 stabilizes MDM2 progenitors•Hyper-editing of 3′ UTR prevents miR-155 binding progenitorsSummaryAdenosine deaminase associated with RNA1 (ADAR1) deregulation contributes to therapeutic resistance many malignancies. Here we show that ADAR1-induced hyper-editing normal human hematopoietic...
Adenosine deaminase acting on RNA1 (ADAR1) preserves genomic integrity by preventing retroviral integration and retrotransposition during stress responses. However, inflammatory-microenvironment-induced ADAR1p110 to p150 splice isoform switching drives cancer stem cell (CSC) generation therapeutic resistance in 20 malignancies. Previously, predicting ADAR1p150-mediated malignant RNA editing represented a significant challenge. Thus, we developed lentiviral ADAR1 splicing reporters for...
Pediatric acute myeloid leukemia (pAML) is typified by high relapse rates and a relative paucity of somatic DNA mutations. Although seminal studies show that splicing factor mutations mis-splicing fuel therapy-resistant stem cell (LSC) generation in adults, deregulation has not been extensively studied pAML. Herein, we describe single-cell proteogenomics analyses, transcriptome-wide analyses FACS-purified hematopoietic progenitor cells followed differential dual-fluorescence lentiviral...
Inflammation-dependent base deaminases promote therapeutic resistance in many malignancies. However, their roles human pre-leukemia stem cell (pre-LSC) evolution to acute myeloid leukemia cells (LSCs) had not been elucidated. Comparative whole-genome and whole-transcriptome sequencing analyses of FACS-purified pre-LSCs from myeloproliferative neoplasm (MPN) patients reveal APOBEC3C upregulation, an increased C-to-T mutational burden, hematopoietic progenitor (HSPC) proliferation during...
Elevated platelet lymphocyte ratio (PLR) and low body mass index (BMI) are associated with inferior survival in non-small cell lung cancer (NSCLC) patients receiving immunotherapy (IO). We evaluated real-world prognostic utility of PLR, BMI, albumin level stage IV NSCLC first line (1L) IO. identified 75 who received 1L IO therapy at USC Norris Comprehensive Cancer Center Los Angeles General Medical from 2015-2022. The primary outcome was overall (OS) time attention to pre-treatment BMI<22,...
Abstract While 5 year survival rates for acute lymphoblastic leukemia (ALL) in childhood are 90% (https://www.cancer.org/cancer/leukemia-in-children/detection-diagnosis-staging/survival-rates.html), myeloid have lagged behind at 65 to 70%. Thus, AML is the leading cause of leukemic mortality and a heterogeneous disease characterized by diverse mutations many occurring low frequencies. Whole exome sequencing analyses not been sufficient predict relapse pediatric patients least part because...
Trisolini et al.1Trisolini R. Bria E. Cetoretta V. Viscuso M. Malapelle U. Seize the opportunity with small tissue samples: tailor teaches.JTO Clin Res Rep. 2023; 4100507Google Scholar raise an important issue in their letter “Seize Opportunity With Small Tissue Samples: The Tailor Teaches!” Notably, they point out that sample sizes and limited sequence panels can provide significant clinical information for patient care decision-making community setting larger are not necessary. Support...
e21092 Background: Meta-analyses show that increasing body mass index (BMI) may be associated with improved overall survival (OS) and progression free (PFS) compared to those lower BMIs in patients receiving immunotherapy (IO). Pretreatment elevated platelet lymphocyte ratio (PLR) has been attributed inferior PFS OS IO. Our study evaluated real world data of Stage IV Non-Small Cell Lung Cancer (NSCLC) first line (1L) treatment regimens involving while evaluating prognostic utility BMI PLR....
Abstract The prevalence of upregulated apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) transcripts as well a distinct mutational signature has been identified and presented extensively in numerous cancer types. Previously, this family cytidine deaminases studied innate immunity, they are active the conversion cytosine to uracil restrict retroviral replication. Recent studies employing whole exome sequencing multiple types have shown significant increase both...
The prevalence of upregulated apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) transcripts as well a distinct mutational signature has been identified and presented extensively in numerous cancer types. Previously, this family cytidine deaminases studied innate immunity, they are active the conversion cytosine to uracil restrict retroviral replication. Recent studies employing whole exome sequencing multiple types have shown significant increase both APOBEC3...
Abstract Introduction: Myeloproliferative neoplasms (MPN) including blast crisis (BC) CML and myelofibrosis (MF) are characterized by the clonal proliferation of hematopoietic cell lineages, mostly in marrow. BC gives rise to TKI resistant myeloid progenitors that activate Wnt/β-catenin signaling pathway. However, BCR-ABL exhibits a robust telomerase activity presents at very low or undetectable level normal cells, plays pivotal role cancer growth may serve as an ideal target for anticancer...
Abstract While inflammation induced ADAR1 RNA deaminases protect the human genome from retroviral integration, deregulation promotes therapeutic resistance in many malignancies. However, combinatorial role of these pre-leukemia stem cell (pre-LSC) evolution to therapy resistant LSC had not been elucidated. Thus, we performed whole sequencing (WGS) analysis 43 CD34+pre-leukemic myeloproliferative neoplasm (MPN) samples compared with matched saliva and non-MPN controls andwhole transcriptome...