A5101867505- Acute Myeloid Leukemia Research
- Protein Tyrosine Phosphatases
- Chronic Lymphocytic Leukemia Research
- Galectins and Cancer Biology
- RNA modifications and cancer
- PI3K/AKT/mTOR signaling in cancer
- Cytokine Signaling Pathways and Interactions
- Chronic Myeloid Leukemia Treatments
- Multiple Myeloma Research and Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Lymphoma Diagnosis and Treatment
- Histone Deacetylase Inhibitors Research
- Kruppel-like factors research
- Mast cells and histamine
- Zebrafish Biomedical Research Applications
- Glycosylation and Glycoproteins Research
- Protein Degradation and Inhibitors
- Cancer-related gene regulation
- Acute Lymphoblastic Leukemia research
- Biochemical and Molecular Research
- MicroRNA in disease regulation
- Advanced Breast Cancer Therapies
- Eosinophilic Disorders and Syndromes
- Epigenetics and DNA Methylation
Stanford University
2018-2024
Arc Research Institute
2023-2024
XCell Science (United States)
2024
Palo Alto Institute
2023-2024
Indiana University – Purdue University Indianapolis
2010-2023
Gilead Sciences (United States)
2017-2023
Indiana University School of Medicine
2008-2018
Perinatal Institute
2005-2016
University of Indianapolis
2016
Indianapolis Zoo
2016
Autosomal dominant hypophosphatemic rickets (ADHR) is unique among the disorders involving Fibroblast growth factor 23 (FGF23) because individuals with R176Q/W and R179Q/W mutations in FGF23 176 RXXR 179 /S 180 proteolytic cleavage motif can cycle from unaffected status to delayed onset of disease. This may occur physiological states associated iron deficiency, including puberty pregnancy. To test role development ADHR phenotype, WT R176Q-Fgf23 knock-in mice were placed on control or...
Abstract Elucidation of the molecular mechanisms underlying carcinogenesis has benefited tremendously from identification and characterization oncogenes tumor suppressor genes. One new advance in this field is PTPN11 as first proto-oncogene that encodes a cytoplasmic tyrosine phosphatase with 2 Src-homology (SH2) domains (Shp2). This was previously shown to play an essential role normal hematopoiesis. More recently, somatic missense gain-of-function mutations have been detected leukemias...
Protein tyrosine phosphatases are often exploited and subverted by pathogenic bacteria to cause human diseases. The phosphatase mPTPB from Mycobacterium tuberculosis is an essential virulence factor that secreted the bacterium into cytoplasm of macrophages, where it mediates mycobacterial survival in host. Consequently, there considerable interest understanding mechanism which evades host immune responses, developing potent selective inhibitors as unique antituberculosis (antiTB) agents. We...
The Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) plays a pivotal role in growth factor and cytokine signaling. Gain-of-function SHP2 mutations are associated with Noonan syndrome, various kinds of leukemias, solid tumors. Thus, there is considerable interest as potential target for anticancer antileukemia therapy. We report salicylic acid based combinatorial library approach aimed at binding both active site unique nearby subpockets enhanced affinity selectivity....
The Src homology 2 domain containing protein tyrosine phosphatase-2 (SHP2) is an oncogenic phosphatase associated with various kinds of leukemia and solid tumors. Thus, there substantial interest in developing SHP2 inhibitors as potential anticancer antileukemia agents. Using a structure-guided fragment-based library approach, we identified novel hydroxyindole carboxylic acid-based inhibitor 11a-1, IC50 value 200 nM greater than 5-fold selectivity against 20 mammalian PTPs. Structural...
During mouse embryogenesis, two waves of hematopoietic progenitors originate in the yolk sac. The first wave consists primitive erythroid that arise at embryonic day 7.0 (E7.0), whereas second definitive E8.25. To determine whether these unilineage from multipotential precursors, we investigated kinetics high proliferative potential colony-forming cells (HPP-CFC), multipotent precursors give rise to macroscopic colonies when cultured vitro. No HPP-CFC were found presomite stages (E6.5-E7.5)....
Dishevelled-associated activator of morphogenesis 1 (Daam1), a member the formin protein family, plays an important role in regulating actin cytoskeleton via mediation linear assembly. Previous functional studies Daam1 lower species suggest its essential Drosophila trachea formation and Xenopus gastrulation. However, vivo physiological function mammalian systems is largely unknown. We have generated Daam1-deficient mice gene-trap technology found that highly expressed developing murine...
Abstract Wnt/β-catenin signaling promotes neural differentiation by activation of the neuron-specific transcription factors, Neurogenin1 (Ngn1), NeuroD, and Brn3a, in nervous system. As neurons cranial sensory ganglia dorsal root transiently express Ngn1, Brn3a during embryonic development, we hypothesized that Wnt proteins could instructively promote a neuronal fate from mesenchymal stem cells (MSCs) directed to differentiate into neurons. Consistent with our hypothesis, Wnt1 induced...
In the rat, p53 promotes tubular apoptosis after ischemic AKI. Acute pharmacologic inhibition of is protective in this setting, but chronic enhances fibrosis, demonstrating that role AKI incompletely understood. Here, we investigated whether genetic absence also Surprisingly, p53-knockout mice (p53(-/-)) had worse kidney injury, compared with wild-type mice, and exhibited increased prolonged infiltration leukocytes ischemia. pifithrin-α mimicked observations p53(-/-) mice. Chimeric lacked...
PURPOSE: To assess the ability of positron emission tomography (PET) scans in differentiating between necrosis and viable seminoma postchemotherapy (PC) residual disease. PATIENTS AND METHODS: We conducted a prospective study 29 patients with at Indiana University. All had PC Computed PET were performed for 19 after primary chemotherapy (group A) 10 salvage B). RESULTS: In group A, masses ≥ 3 cm 14 patients, less than three not quantified two patients. A negative scan results have stable or...
Oncogenic mutations of FLT3 and KIT receptors are associated with poor survival in patients acute myeloid leukemia (AML) myeloproliferative neoplasms (MPNs), currently available drugs largely ineffective. Although Stat5 has been implicated regulating several lymphoid malignancies, how precisely regulates leukemogenesis, including its nuclear translocation to induce gene transcription, is poorly understood. In leukemic cells, we show constitutive activation focal adhesion kinase (FAK) whose...
Ferritin, a 24-mer heteropolymer of heavy (H) and light (L) subunits, is the main cellular iron storage protein plays pivotal role in homeostasis by modulating free levels thus reducing radical-mediated damage. The H subunit has ferroxidase activity (converting Fe(II) to Fe(III)), while L promotes nucleation increases ferritin stability. Previous studies on gene (Fth) mice have shown that complete inactivation Fth lethal during embryonic development, without ability compensate subunit. In...
Juvenile myelomonocytic leukemia is a rare myeloproliferative disease in young children. While hematopoietic stem cell transplantation remains the only curative therapeutic option for most patients, children with juvenile increasingly receive novel agents phase I–II clinical trials as pre-transplant therapy or relapse after transplantation. However, response criteria definitions of outcome standardized evaluation treatment effect patients are currently lacking. Here we propose to evaluate...
Noonan syndrome (NS) is an autosomal dominant congenital disorder characterized by multiple birth defects including heart and myeloproliferative disease (MPD). Approximately 50% of NS patients have germline gain-of-function mutations in PTPN11, which encodes the protein-tyrosine phosphatase, Shp2. We provide evidence that conditional ablation Stat3 hematopoietic cells cardiac valvular tissues leads to myeloid progenitor hyperplasia pulmonary stenosis due leaflet thickening, respectively....
Abstract The asymmetric organization of epithelial cells is a basic counter to cellular proliferation. However, the mechanisms whereby pro-growth pathways are modulated by intracellular factors that control cell shape not well understood. This study demonstrates adaptor protein Amot, in addition its established role regulating asymmetry, also promotes extracellular signal-regulated kinase 1 and 2 (ERK1/2)–dependent proliferation mammary cells. Specifically, expression Amot80, but mutant...