A5007618693- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- HIV/AIDS drug development and treatment
- Cancer Genomics and Diagnostics
- Ubiquitin and proteasome pathways
- Computational Drug Discovery Methods
- Cancer Mechanisms and Therapy
- Chemokine receptors and signaling
- Peptidase Inhibition and Analysis
- Glycosylation and Glycoproteins Research
- Chemical Synthesis and Analysis
- Epigenetics and DNA Methylation
- Chronic Myeloid Leukemia Treatments
- Immune Cell Function and Interaction
- Malaria Research and Control
- Monoclonal and Polyclonal Antibodies Research
- Chromatin Remodeling and Cancer
- Semantic Web and Ontologies
- Genomics and Rare Diseases
- CAR-T cell therapy research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Chromosomal and Genetic Variations
- Histone Deacetylase Inhibitors Research
- Advanced Database Systems and Queries
- Myeloproliferative Neoplasms: Diagnosis and Treatment
University of Arkansas for Medical Sciences
2015-2024
Miami Children's Hospital
2024
Winthrop Rockefeller Foundation
2019-2023
Western University
1985-2023
Novartis (Switzerland)
2023
University of Arkansas at Fayetteville
2017
Drees & Sommer (Germany)
2013
University of Arkansas at Little Rock
2009-2012
University Hospital Ulm
2011
Bassett Healthcare Network
2005
Patients with newly diagnosed multiple myeloma (NDMM) high-risk disease are in need of new treatment strategies to improve the outcomes. Multiple clinical, cytogenetic, or gene expression features have been used identify patients, each which has significant weaknesses. Inclusion molecular into risk stratification could resolve current challenges. In a genome-wide analysis largest set and clinical data established date from NDMM, as part Myeloma Genome Project, we defined DNA drivers...
Abstract In multiple myeloma malignant plasma cells expand within the bone marrow. Since this site is well-perfused, a rapid dissemination of “fitter” clones may be anticipated. However, an imbalanced distribution frequently observed in medical imaging. Here, we perform multi-region sequencing, including iliac crest and radiology-guided focal lesion specimens from 51 patients to gain insight into spatial clonal architecture. We demonstrate genomic heterogeneity more than 75% patients,...
Smoldering myeloma (SMM) is associated with a high-risk of progression to (MM). We report the results study 82 patients both targeted sequencing that included capture immunoglobulin and MYC regions. By comparing these newly diagnosed (MM) we show fewer NRAS FAM46C mutations together adverse translocations, del(1p), del(14q), del(16q), del(17p) in SMM consistent their role as drivers transition MM. KRAS are shorter time (HR 3.5 (1.5-8.1), p = 0.001). In an analysis change clonal structure...
Deciphering Multiple Myeloma evolution in the whole bone marrow is key to inform curative strategies. Here, we perform spatial-longitudinal whole-exome sequencing, including 140 samples collected from 24 patients during up 14 years. Applying imaging-guided sampling observe three evolutionary patterns, relapse driven by a single-cell expansion, competing/co-existing sub-clones, and unique sub-clones at distinct locations. While do not find sub-clone baseline focal lesion(s), show close...
Background The tumor microenvironment (TME) is increasingly appreciated as an important determinant of cancer outcome, including in multiple myeloma (MM). However, most studies have been based on bone marrow (BM) aspirates, which often do not fully reflect the cellular content BM tissue itself. To address this limitation research, we systematically characterized whole (WBM) during premalignant, baseline, treatment, and post-treatment phases. Methods findings Between 2004 2019, 998 samples...
Abstract Early alterations within the bone marrow microenvironment that contribute to progression of multiple myeloma (MM) from its precursor stages could be key identifying novel therapeutic approaches. However, intrinsic variability in cellular populations between patients and differences sample processing analysis methods have made it difficult identify consistent changes data sets. Here, we used single-cell RNA sequencing cells stages, monoclonal gammopathy unknown significance,...
Abstract The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted 578 individuals with plasma cell neoplasms the FoundationOne Heme identified relevant abnormalities novel markers. Mutational burden was associated maf proliferation gene expression groups, high-mutational poor prognosis. homozygous deletions that were present myeloma within key genes, including CDKN2C , RB1,...
is a widely acting transcription factor and its deregulation crucial event in many human cancers.
Copy-number changes and translocations have been studied extensively in many datasets with long-term follow-up. The impact of mutations remains debated given the short time to follow-up most datasets.We performed targeted panel sequencing covering 125 myeloma-specific genes loci involved 223 newly diagnosed myeloma samples recruited into one total therapy trials.As expected, commonly mutated were NRAS, KRAS, BRAF, making up 44% patients. Double-Hit BRAF DIS3 had an on outcome alongside...
Multiple myeloma (MM) growth is supported by an immune-tolerant bone marrow microenvironment. Here, we find that loss of Never in mitosis gene A (NIMA)-related kinase 2 (NEK2) tumor microenvironmental cells associated with MM suppression. The absence NEK2 leads to both fewer tumor-associated macrophages (TAMs) and inhibitory T cells. expression myeloid progenitor promotes the generation functional TAMs when stimulated conditional medium. Clinically, high increased CD8+ effector memory cells,...
Symptoms and changes in pulmonary function of subjects with chronic obstructive disease (COPD) elderly normal subjects, induced by a 4-h exposure to 0.3 ppm NO2, were investigated using double-blind, crossover design purified air. The 5-day experimental protocol required approximately 2 wk at least separation between randomized exposures either NO2 or air which included several periods exercise. Over 2-yr period, COPD all history smoking, consisting 13 men 7 women (mean age 60.0 yr) 20...
Background/Objectives: Accurately estimating survival times for kidney cancer patients is critical clinical decision-making, treatment evaluation, resource allocation other purposes. Yet data from relatively recent diagnosis cohorts presents an important difficulty: five, 10 or 20-year time averages are not available until 5, 20 years later, which may be in the future thus presenting a challenge to understand present. The proposed approach shown but could applied problems connected types of...
Chromosome 1 (chr1) copy-number abnormalities (CNA) and structural variants (SV) are frequent in newly diagnosed multiple myeloma (NDMM) associated with a heterogeneous impact on outcomes, the drivers of which largely unknown.A multiomic approach comprising CRISPR, gene mapping CNAs SVs, methylation, expression, mutational analysis was used to document extent chr1 molecular their pathway utilization.We identified two distinct groups gain(1q): focal gains limited gene-expression changes...
Abstract Treating and imaging patients in the upright orientation is gaining acceptance radiation oncology radiology has distinct advantages over recumbent position. An IRB approved study to investigate positions orientations of male pelvic organs between supine was conducted. The comprised scanning 15 volunteers (aged 55–75 years) on a 0.6 T Fonar MRI scanner with full bladder position an empty bladder. Pelvic revealed that 1. Position shape prostate are not impacted significantly by fill....
Abstract Tumor immune microenvironmental alterations occur early in multiple myeloma (MM) development. In this study, we aim to systematically characterize the tumor microenvironment (TME) and tumor-immune interactions from precursor stages, i.e., monoclonal gammopathy of undetermined significance (MGUS) smoldering MM (SMM), newly diagnosed MM, comparing these healthy donors. Using CIBERSORT, mass cytometry (CyTOF), single-cell RNA sequencing (scRNA-Seq), examined innate adaptive changes...
Background MicroRNAs are regulators of gene expression, which act mainly by decreasing mRNA levels their multiple targets. Deregulated microRNA expression has been shown for acute myeloid leukemia, a disease also characterized altered associated with distinct genomic aberrations such as nucleophosmin (NPM1) mutations. To shed further light on the role deregulated and in cytogenetically normal leukemia NPM1 mutation we performed an integrative analysis data sets.Design Methods Both profiles...
Chromosomal rearrangements that result in oncogenic kinase activation are present many solid and hematological malignancies, but none have been reported multiple myeloma (MM). Here we analyzed 1421 samples from 958 patients using a targeted assay detected fusion genes 1.5% of patients. These were in-frame the majority them contained domains either receptor tyrosine kinases (ALK, ROS1, NTRK3, FGFR1) or cytoplasmic (BRAF, MAP3K14, MAPK14), which would MEK/ERK, NF-κB, inflammatory signaling...
Abstract Background Multiple Myeloma (MM) is a hematological malignancy with genomic heterogeneity and poor survival outcome. Apart from the central role of genetic lesions, epigenetic anomalies have been identified as drivers in development disease. Methods Alterations DNA methylome were mapped 52 newly diagnosed MM (NDMM) patients six molecular subgroups matched loci-specific chromatin marks to define their impact on gene expression. Differential methylation analysis was performed using...