A5041364551- Acute Myeloid Leukemia Research
- Retinoids in leukemia and cellular processes
- Histiocytic Disorders and Treatments
- Biological Activity of Diterpenoids and Biflavonoids
- Extracellular vesicles in disease
- RNA modifications and cancer
- Phytochemical compounds biological activities
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Natural Compounds in Disease Treatment
- Plant biochemistry and biosynthesis
- Peroxisome Proliferator-Activated Receptors
- Cancer, Hypoxia, and Metabolism
- Parvovirus B19 Infection Studies
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Autophagy in Disease and Therapy
- Metal complexes synthesis and properties
- CAR-T cell therapy research
- Cancer Treatment and Pharmacology
- Histone Deacetylase Inhibitors Research
- Autoimmune and Inflammatory Disorders Research
Cincinnati Children's Hospital Medical Center
2012-2024
Immune Deficiency Foundation
2015-2020
University of Cincinnati
2013
University of Cincinnati Medical Center
2013
Maryville University
2013
Texas Oncology
2013
Miami University
2010
Many patients with histiocytic disorders such as Langerhans cell histiocytosis (LCH) or Erdheim-Chester disease (ECD) have treatment-refractory suffer recurrences. Recent findings of gene mutations in histiocytoses generated options for targeted therapies. We sought to determine the utility prospective sequencing select genes further characterize and identify therapies histiocytoses. Biopsies 72 a variety underwent comprehensive genomic profiling DNA RNA sequencing. Fifteen (21%) carried...
Abstract Despite growing awareness of the biologic features underlying MLL-rearranged leukemia, targeted therapies for this leukemia have remained elusive and clinical outcomes remain dismal. MBNL1, a protein involved in alternative splicing, is consistently overexpressed leukemias. We found that MBNL1 loss significantly impairs propagation murine human vitro vivo. Through transcriptomic profiling our experimental systems, we show leukemic cells, regulates splicing (predominantly intron...
Recently, macroautophagy/autophagy has emerged as a promising target in various types of solid tumor treatment. However, the impact autophagy on acute myeloid leukemia (AML) maintenance and validity viable AML therapy remain unclear. Here we show that Kmt2a/Mll-Mllt3/Af9 (MA9-AML) cells have high flux compared with normal bone marrow cells, but autophagy-specific targeting, either through Rb1cc1-disruption to abolish initiation, or via Atg5-disruption prevent phagophore (the autophagosome...
Abstract Purpose: Classical pharmacology allows the use and development of conventional phytomedicine faster more economically than drugs. This approach should be tested for their efficacy in terms complementarity disease control. The purpose this study was to determine molecular mechanisms by which nimbolide, a triterpenoid found well-known medicinal plant Azadirachta indica, controls glioblastoma growth. Experimental Design: Using vitro signaling, anchorage-independent growth, kinase...
Abstract Langerhans cell histiocytosis (LCH) is a rare hematologic neoplasm characterized by clonal proliferation of Langerhans-like cells. Genomic profiling has identified recurrent somatic activating mutations in the mitogen-activated protein kinase pathway, which are targetable small-molecule inhibitors. However, key questions such as curative potential targeted therapy and origin remain unanswered. In this study, we describe clinical outcomes series pediatric patients with multisystem...
Although great advances have been made in understanding the pathobiology of mixed lineage leukemia-rearranged (MLL-r) leukemias, therapies for this leukemia remained limited, and clinical outcomes remain bleak. In order to identify novel targets immunotherapy treatments, we compiled a lineage-independent MLL-r gene signature using publicly available data sets. Data from large repositories were filtered through silico human surfaceome, providing list highly predicted cell surface proteins...
Abstract Certain subtypes of pediatric leukemia continue to have dismal cure rates despite advances in targeted therapy. One such disease is acute megakaryoblastic (AMKL) with a rearrangement ETO2/GLIS2 (also known as CBFA2T3/GLIS2.) Based on our preliminary data utilizing CRISPR/Cas9 screens vivo patient-derived xenografts, we nominated IGF2BP1 potential vulnerability ETO2/GLIS2-rearranged AMKL. For discovery phase, utilized E2G2r AMKL which successfully engrafts NSGS mice. We created...
<p>PDF file - 71K</p>
<p>PDF file - 71K</p>
<p>PDF file - 312K, Nimbolide is more cytotoxic than many other chemotherapy agents. (A) Cell proliferation assay showing viability of GBM cells in the presence Temozolomide (TMZ) for 72 hours. (B) effect comparison with chemotherapeutic Data representative two independent experiments. +p ≤ 0.05; *p 0.001.</p>
<div>Abstract<p><b>Purpose:</b> Classical pharmacology allows the use and development of conventional phytomedicine faster more economically than drugs. This approach should be tested for their efficacy in terms complementarity disease control. The purpose this study was to determine molecular mechanisms by which nimbolide, a triterpenoid found well-known medicinal plant <i>Azadirachta indica</i>, controls glioblastoma...
<div>Abstract<p><b>Purpose:</b> Classical pharmacology allows the use and development of conventional phytomedicine faster more economically than drugs. This approach should be tested for their efficacy in terms complementarity disease control. The purpose this study was to determine molecular mechanisms by which nimbolide, a triterpenoid found well-known medicinal plant <i>Azadirachta indica</i>, controls glioblastoma...
<p>PDF file - 312K, Nimbolide is more cytotoxic than many other chemotherapy agents. (A) Cell proliferation assay showing viability of GBM cells in the presence Temozolomide (TMZ) for 72 hours. (B) effect comparison with chemotherapeutic Data representative two independent experiments. +p ≤ 0.05; *p 0.001.</p>