A5063698376- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Multiple Myeloma Research and Treatments
- Histone Deacetylase Inhibitors Research
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Cancer Genomics and Diagnostics
- Eosinophilic Disorders and Syndromes
- Kruppel-like factors research
- Phagocytosis and Immune Regulation
- Cellular Mechanics and Interactions
- Pancreatic function and diabetes
- Cytokine Signaling Pathways and Interactions
- Venous Thromboembolism Diagnosis and Management
- Cardiac tumors and thrombi
- Genomic variations and chromosomal abnormalities
- Epigenetics and DNA Methylation
- CAR-T cell therapy research
- Protein Degradation and Inhibitors
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neuropeptides and Animal Physiology
- Acute Lymphoblastic Leukemia research
- Genetics, Aging, and Longevity in Model Organisms
- Glycosylation and Glycoproteins Research
- HER2/EGFR in Cancer Research
Kosair Children's Hospital
2025
University of Louisville
2025
Scripps MD Anderson Cancer Center
2025
Memorial Sloan Kettering Cancer Center
2017-2024
The University of Texas MD Anderson Cancer Center
2024
Kettering University
2022-2024
AbbVie (United States)
2024
Blueprint Medicines (United States)
2024
Merck (Singapore)
2024
Bristol-Myers Squibb (Germany)
2024
Abstract Two types of acquired loss heterozygosity are possible in cancer: deletions and copy-neutral uniparental disomy (UPD). Conventionally, copy number losses identified using metaphase cytogenetics, whereas detection UPD is accomplished by microsatellite analysis as such, not often used clinically. Recently, introduction single nucleotide polymorphism (SNP) microarrays has allowed for the systematic sensitive hematologic malignancies other cancers. In this study, we have applied 250K...
The classic Philadelphia chromosome–negative myeloproliferative neoplasms (MPN) consist of myelofibrosis, polycythemia vera, and essential thrombocythemia are a heterogeneous group clonal blood disorders characterized by an overproduction cells. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MPN were developed as result meetings convened multidisciplinary panel with expertise MPN, the goal providing recommendations management adults. include diagnostic workup, risk...
Acquired somatic uniparental disomy (UPD) is commonly observed in myelodysplastic syndromes (MDS), myelodysplastic/myeloproliferative neoplasms (MDS/MPN), or secondary acute myelogenous leukemia (sAML) and may point toward genes harboring mutations. Recurrent UPD11q led to identification of homozygous mutations c-Cbl, an E3 ubiquitin ligase involved attenuation proliferative signals transduced by activated receptor tyrosine kinases. We examined the role frequency Cbl gene family MPN related...
Pulmonary fibrosis can be experimentally induced in small rodents by bleomycin. The antibiotic is usually administered via the intratracheal or intranasal routes. In present study, we investigated oropharyngeal aspiration of bleomycin as an alternative route for induction lung rats and mice. development injury was followed vivo ultrashort echo time magnetic resonance imaging (UTE-MRI) post-mortem analyses (histology collagen, hydroxyproline determination, qRT-PCR). C57BL/6 mice, led to more...
Abstract Gain-of-function mutations activating JAK/STAT signaling are seen in the majority of patients with myeloproliferative neoplasms (MPN), most commonly JAK2V617F. Although clinically approved JAK inhibitors improve symptoms and outcomes MPNs, remissions rare, mutant allele burden does not substantively change chronic therapy. We hypothesized this is due to limitations current potently specifically abrogate JAK2 signaling. therefore developed a conditionally inducible mouse model...
Abstract A key to enhance the low translatability of preclinical drug discovery are in vitro human three-dimensional (3D) microphysiological systems (MPS). Here, we show a new method for automated engineering 3D skeletal muscle models microplates and functional compound screening address lack wasting disease medication. To this end, adapted our recently described 24-well plate bioprinting platform with printhead cooling system allow microvalve-based drop-on-demand printing cell-laden...
Betacellulin belongs to the family of epidermal growth factor-like factors that are expressed as transmembrane precursors and undergo proteolytic ectodomain shedding release a soluble mature factor. In this study, we investigated betacellulin precursor (pro-BTC) in conditionally immortalized wild-type (WT) ADAM-deficient cell lines. Sequential cleavage predominant cell-surface 40-kDa form pro-BTC generated major (26-28 kDa) two minor (20 15 forms cellular remnant lacking (12 kDa). Pro-BTC...
We applied single nucleotide polymorphism arrays (SNP-A) to study karyotypic abnormalities in patients with atypical myeloproliferative syndromes (MPD), including myeloproliferative/myelodysplastic syndrome overlap both positive and negative for the JAK2 V617F mutation secondary acute myeloid leukemia (AML). In typical MPD cases (N = 8), which served as a control group, those homozygous showed clear uniparental disomy (UPD) of 9p using SNP-A. Consistent possible genomic instability, 19/30...
Eosinophilic disorders and related syndromes represent a heterogeneous group of neoplastic nonneoplastic conditions, characterized by more eosinophils in the peripheral blood, may involve eosinophil-induced organ damage. In WHO classification myeloid lymphoid neoplasms, eosinophilic dysregulated tyrosine kinase (TK) fusion genes are recognized as new category termed, myeloid/lymphoid neoplasms with eosinophilia rearrangement PDGFRA , PDGFRB or FGFR1 PCM1-JAK2 . addition to these...
Idiopathic pulmonary fibrosis is a progressive and lethal disease, characterized by loss of lung elasticity alveolar surface area, secondary to epithelial cell injury, reactive inflammation, proliferation fibroblasts, deposition extracellular matrix. The effects oropharyngeal aspiration bleomycin in Sprague-Dawley rats C57BL/6 mice, as well intratracheal administration ovalbumin actively sensitized Brown Norway on total volume assessed noninvasively magnetic resonance imaging (MRI) were...
Progressive loss of muscle mass and function due to fiber atrophy in the elderly chronically ill is now defined as sarcopenia. It a major contributor independence, disability, need long-term care well overall mortality. Sarcopenia heterogenous disease underlying mechanisms are not completely understood. Here, we newly identified used Tmem158, alongside Cdkn1a, relevant senescence denervation markers (SDMs), associated with atrophy. Subsequent application laser capture microdissection (LCM)...
Accurate classification and risk stratification are critical for clinical decision making in patients with acute myeloid leukemia (AML). In the newly proposed World Health Organization International Consensus classifications of hematolymphoid neoplasms, presence myelodysplasia-related (MR) gene mutations is included as 1 diagnostic criteria AML, AML-MR, based largely on assumption that these specific AML an antecedent myelodysplastic syndrome. ICC also prioritizes MR over ontogeny (as...
Enasidenib (ENA) is an inhibitor of isocitrate dehydrogenase 2 (IDH2) approved for the treatment patients with IDH2-mutant relapsed/refractory acute myeloid leukemia (AML). In this phase 2/1b Beat AML substudy, we applied a risk-adapted approach to assess efficacy ENA monotherapy aged ≥60 years newly diagnosed in whom genomic profiling demonstrated that mutant IDH2 was dominant leukemic clone. Patients did not induce complete remission (CR) or CR incomplete blood count recovery (CRi)...
CD33 is a tractable target in acute myeloid leukemia (AML) for chimeric antigen receptor (CAR) T cell therapy, but clinical success lacking. We developed 3P14HLh28Z, novel CD33-directed CD28/CD3Z-based CAR derived from high-affinity binder obtained through membrane-proximal fragment immunization humanized mice. found that exclusively with the domain of necessary identification binders Compared clinically validated lintuzumab-based cells targeting distal epitopes, 3P14HLh28Z showed enhanced...
Summary Double‐negative (DN) regulatory T cells (Tregs) are specialized lymphocytes involved in the down‐modulation of immune responses, resulting allotolerance after allogeneic haematopoietic stem cell transplantation (HSCT). Most properties DN Tregs were identified murine models, including unique ability to suppress alloreactive syngeneic effector an antigen‐specific manner via Fas/Fas‐ligand interactions. We investigated behaviour following human HSCT with regard occurrence...