A5042919966- Chronic Lymphocytic Leukemia Research
- Galectins and Cancer Biology
- Lymphoma Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- MicroRNA in disease regulation
- Phagocytosis and Immune Regulation
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- Glycosylation and Glycoproteins Research
- Viral-associated cancers and disorders
- Pluripotent Stem Cells Research
- Single-cell and spatial transcriptomics
- Monoclonal and Polyclonal Antibodies Research
- Acute Lymphoblastic Leukemia research
- Extracellular vesicles in disease
- Renal and related cancers
- Acute Myeloid Leukemia Research
- CAR-T cell therapy research
- Neuroinflammation and Neurodegeneration Mechanisms
- Chronic Myeloid Leukemia Treatments
- Congenital heart defects research
- Systemic Lupus Erythematosus Research
- Circular RNAs in diseases
- Immune cells in cancer
- Cell Image Analysis Techniques
National Institutes of Health
2016-2024
National Heart Lung and Blood Institute
2016-2024
Rutgers, The State University of New Jersey
2011-2016
Rutgers New Jersey Medical School
2011-2014
Rutgers Health
2014
University Hospital, Newark
2011-2012
Abstract Treatment of chronic lymphocytic leukemia (CLL) has shifted from chemo-immunotherapy to targeted agents. To define the evolutionary dynamics induced by therapy in CLL, we perform serial exome and transcriptome sequencing for 61 ibrutinib-treated CLLs. Here, report clonal shifts (change >0.1 cancer cell fraction, Q < 0.1) 31% patients during first year therapy, associated with adverse outcome. We also observe transcriptional downregulation pathways mediating energy metabolism,...
To determine the role of CD49d for response to Bruton's tyrosine kinase inhibitors (BTKis) in patients with chronic lymphocytic leukemia (CLL).In treated acalabrutinib (n=48), expression, VLA-4 integrin activation, and tumor transcriptomes CLL cells were assessed. Clinical responses BTKis investigated (n=48; NCT02337829), ibrutinib (n=73; NCT01500733) patients.In acalabrutinib, treatment induced lymphocytosis was comparable both subgroups but resolved more rapidly CD49d+ cases. Acalabrutinib...
Abstract The clinical efficacy displayed by ibrutinib in chronic lymphocytic leukemia (CLL) has been challenged the frequent emergence of resistant clones. target, Bruton's tyrosine kinase (BTK), is essential for B-cell receptor signaling, and most cases carry mutations BTK or PLCG2, a downstream effector target BTK. Recent findings show that MI-2, small molecule inhibitor para-caspase MALT1, effective preclinical models another type BCR pathway–dependent lymphoma. We therefore studied...
Abstract Bruton tyrosine kinase inhibitors (BTKis) have transformed the treatment landscape for patients with chronic lymphocytic leukemia (CLL). BTKis target pathways critical CLL cell survival and proliferation. We evaluated effects of on transcriptome composition tumor microenvironment (TME) in CLL. Lymph node (LN) biopsies from 65 treated ibrutinib (n=35) collected pre-treatment at 24 72 hours first dose or acalabrutinib (n=30) after 3 days 4, 12, 24, 36 last drug were submitted RNA...
In single-cell RNA-sequencing analysis, clustering cells into groups and differentiating cell by differentially expressed (DE) genes are 2 separate steps for investigating identity. However, the ability to differentiate between could be affected clustering. This interdependency often creates a bottleneck in analysis pipeline, requiring researchers repeat these multiple times setting different parameters identify set of that more differentiated biologically relevant.To accelerate this...
In both human chronic lymphocytic leukemia (CLL) and the New Zealand Black (NZB) murine model of CLL, decreased levels microRNAs miR-15a/16 play an important role in disease. Here we investigate effects this microRNA on early steps B cell development capacity miR-15a-deficient hematopoietic stem cells (HSC) B1 progenitor (B1P) to reproduce CLL-like phenotype vitro vivo. Our results demonstrate that miR-15a deficient HSC B1P are capable repopulating irradiated recipients produce higher...
Common blood disorders include hematopoietic cell malignancies or leukemias and plasma dyscrasia, all of which have associated microRNA abnormalities. In this paper, we discuss several including acute myeloid leukemia (AML) chronic lymphocytic (CLL) identify altered microRNAs their targets. Immune with levels antibodies autoimmune disorders, such as systemic lupus erythematosus (SLE) anti-self-autoantibodies immunoglobulin A nephropathy (IgAN) also related The alterations in may serve...
According to the endosymbiotic hypothesis, precursor of mitochondria invaded eukaryotic cells, a process that began roughly 2 billion years ago. Since then, majority genetic material translocated from nucleus, where now almost all mitochondrial proteins are expressed. Only tiny amount DNA remained in mitochondria, known as (mtDNA). In this study, we report transfer mtDNA fragments nucleus pluripotent stem cells is still ongoing. We show by situ hybridization and agarose two-dimensional gel...
New Zealand Black (NZB) mice, a de novo model of CLL, share multiple characteristics with CLL patients, including decreased expression miR-15a/16-1. We previously discovered point mutation and deletion in the 3' flanking region mir-16-1 NZB similar has been found small number patients. However, it was unknown whether is cause for reduced miR-15a/16-1 development. Using PCR vitro microRNA processing assays, we that sequence alterations mir-15a/16-1 loci result deficient precursor forms...
Abstract Progressive disease (PD) in patients with chronic lymphocytic leukemia (CLL) on ibrutinib often presents acquired mutations BTK and/or PLCG2. Reported variant allele frequencies (VAF) are low, leading some to question the role of these mutations. Further, several co-existing identified. Here we investigated clonal composition PD single cell level, across time, and different anatomic compartments. 84 CLL (52 treatment-naïve; 32 relapsed/refractory) either a TP53 aberration or age ≥65...
<div>Abstract<p>Purpose: To determine the role of CD49d for response to Bruton’s tyrosine kinase inhibitors (BTKis) in patients with chronic lymphocytic leukemia (CLL). Methods: In treated acalabrutinib (n=48), expression, VLA-4 integrin activation, and tumor transcriptomes CLL cells were assessed. Clinical responses BTKis investigated (n=48; NCT02337829), ibrutinib (n=73; NCT01500733) patients. Results: acalabrutinib, treatment induced lymphocytosis was comparable both subgroups...
<p>Supplementary Figure S3. In vivo effect of acalabrutinib on the VLA-4 activation upon BCR and chemokine signaling</p>
<p>Supplementary Figure S5. Time to disease progression, prevalence of resistance mutations, and risk category by CLL-4 model</p>
<p>Supplementary Figure S3. In vivo effect of acalabrutinib on the VLA-4 activation upon BCR and chemokine signaling</p>