A5056952708- Signaling Pathways in Disease
- MicroRNA in disease regulation
- Erythrocyte Function and Pathophysiology
- Cancer-related molecular mechanisms research
- Peptidase Inhibition and Analysis
- Extracellular vesicles in disease
- RNA modifications and cancer
- PARP inhibition in cancer therapy
- Fungal and yeast genetics research
- Cellular transport and secretion
- Nuclear Receptors and Signaling
- Caveolin-1 and cellular processes
- DNA Repair Mechanisms
- Cancer Cells and Metastasis
- RNA regulation and disease
- Cellular Mechanics and Interactions
- Nerve injury and regeneration
- Sirtuins and Resveratrol in Medicine
- Ferroptosis and cancer prognosis
- Acute Myeloid Leukemia Research
- Circular RNAs in diseases
- Epigenetics and DNA Methylation
- Insect Resistance and Genetics
- Microtubule and mitosis dynamics
- Neuroscience and Neuropharmacology Research
University of Maryland, Baltimore
2013-2023
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center
2008-2022
Institute for Stem Cell Biology and Regenerative Medicine
2021
University of Baltimore
2017-2021
U-M Rogel Cancer Center
2014
Johns Hopkins University
1997-2006
Virginia Tech
1994
Down syndrome is one of the major causes mental retardation and congenital heart malformations. Other common clinical features include gastrointestinal anomalies, immune system defects Alzheimer’s disease pathological neurochemical changes. The most likely consequence presence three copies chromosome 21 overexpression its resident genes, a fact which must underlie pathogenesis abnormalities that occur in syndrome. Here we show DSCR1, product gene highly expressed brain, skeletal muscle,...
Ca 2+ signals regulate gene expression in animal and yeast cells through mechanisms involving calcineurin, a protein phosphatase activated by binding calmodulin. Tcn1p, also named Crz1p, was identified as transcription factor required for the calcineurin-dependent induction of PMC1, PMR1, PMR2A, FKS2 which confer tolerance to high , Mn Na + cell wall damage, respectively. Tcn1p not other processes, such inhibition vacuolar H /Ca exchanger pheromone-stimulated uptake system, suggesting that...
The protein phosphatase calcineurin mediates many cellular responses to calcium signals. Using a genetic screen in yeast, we identified new family of proteins conserved fungi and animals that inhibit function when overexpressed. Overexpression the yeast Rcn1p or human homologs DSCR1 ZAKI-4 inhibited two independent functions yeast: activation transcription factor Tcn1p inhibition H + /Ca 2+ exchanger Vcx1p. Purified recombinant bound vitro its activity. Signaling via calmodulin, calcineurin,...
Kinesin-related Cin8p is the most important spindle-pole-separating motor in Saccharomyces cerevisiae but not essential for cell viability. We identified 20 genes whose products are specifically required by deficient Cin8p. All associated with mitotic roles and represent at least four different functional pathways. These include act two spindle pathways that overlap function Cin8p, kinesin-related Kip1p pathway cytoplasmic dynein pathway. In addition, checkpoint normal microtubule stability...
The conserved RCN family of proteins can bind and directly regulate calcineurin, a Ca 2+ -activated protein phosphatase involved in immunity, heart growth, muscle development, learning, other processes. Whereas high levels RCNs inhibit calcineurin signaling fungal animal cells, also stimulate when expressed at endogenous levels. Here we show that the stimulatory effect yeast Rcn1 involves phosphorylation conservedserine residue by Mck1, member GSK-3 kinases. Mutations consensus site human...
Bi-allelic GBA1 mutations cause Gaucher's disease (GD), the most common lysosomal storage disorder. Neuronopathic manifestations in GD include neurodegeneration, which can be severe and rapidly progressive. are also frequent genetic risk factors for Parkinson's disease. Dysfunction of autophagy-lysosomal pathway represents a key pathogenic event GBA1-associated neurodegeneration. Using an induced pluripotent stem cell (iPSC) model GD, we previously demonstrated that alterations neurons...
Summary Expression levels of MIR 144 and 451 increase during erythropoiesis, a pattern that is conserved from zebrafish to humans. As these two mi R s are expressed the same polycistronic transcript, we manipulated in human erythroid cells individually together investigate their effects on erythropoiesis. Inhibition endogenous resulted decreased numbers ( CD 71 hi 235a 34 − ) cells, consistent with prior studies mice. In addition, inhibition impaired differentiation, unlike mouse where...
Cardiac fibrosis is a hallmark in late-stage familial dilated cardiomyopathy (DCM) patients, although the underlying mechanism remains elusive. exosomes (Exos) have been reported relating to ischemic cardiomyopathy. Thus, we investigated whether Exos secreted from DCM cardiomyocytes could promote fibrogenesis. Using human iPSCs differentiated isolated of angiotensin II stimulation conditioned media either or control (CTL) cardiomyocytes. Of interest, cultured cardiac fibroblasts had...
Kinesin-5 motor proteins are evolutionarily conserved and perform essential roles in mitotic spindle assembly elongation during anaphase. Previous studies demonstrated a specialized homotetrameric structure with two pairs of catalytic domains, one at each end dumbbell-shaped molecule. This suggests that they their by cross-linking sliding antiparallel microtubules. However, the exact kinesin-5 sequence elements important for formation tetrameric complexes have not yet been identified. In...
Stem cell cultures within perfusion bioreactors, while efficient in obtaining numbers, often lack the similarity to native tissues and consequently phenotype. We develop a three-dimensional (3D)-printed fluidic chamber for dynamic stem culture, with emphasis on control over flow substrate curvature 3D environment, two physiologic features of tissues. The geometry, consisting an array vertical cylindrical pillars, facilitates actin-mediated localization human mesenchymal cells (hMSCs) ∼200 μm...
The neurotrophin brain-derived neurotrophic factor (BDNF), via activation of its receptor, tyrosine receptor kinase B (trkB), regulates a wide variety cellular processes in the nervous system, including neuron survival and synaptic plasticity. Although expression BDNF is known to be Ca2+-dependent, regulation trkB has not been extensively studied. Here we report that depolarization cultured mouse cortical neurons increased full-length, catalytically active isoform without affecting truncated...
Viral proteins must intimately interact with the host cell machinery during virus replication. Here, we used yeast Saccharomyces cerevisiae as a system to identify novel functional interactions between viral and eukaryotic cells. Our work demonstrates that when Middle East respiratory syndrome coronavirus (MERS-CoV) ORF4a accessory gene is expressed in it causes slow-growth phenotype. has been characterized an interferon antagonist mammalian cells, yet lack system, suggesting further Using...
Radiation therapy plays a major role in the treatment of lung cancer patients. However, cells develop resistance to radiation. Tumor radioresistance is complex multifactorial mechanism which may be dependent on DNA damage and repair, hypoxic conditions inside tumor microenvironment, clonal selection radioresistant from heterogeneous site, it cause failure non–small cell (NSCLC). In present investigation caveolin-1 ( CAV-1 ) has been observed highly expressed radiation resistant A549 cells....
DNA methyltransferase inhibitors (DNMTis) reexpress hypermethylated genes in cancers and leukemias also activate endogenous retroviruses (ERVs), leading to interferon (IFN) signaling, a process known as viral mimicry. In the present study we show that subset of acute myeloid (AMLs) with mutations
Abstract Cyclic AMP response element binding protein (CREB) functions as an activity‐dependent transcription factor in the nervous system. Increases intracellular Ca 2+ due to neuronal activity lead phosphorylation and subsequent activation of CREB. Although CREB at Ser‐133 is necessary for stimulation transcriptional activity, it not sufficient. Here we demonstrate that mouse cortical neurons, inhibition ‐dependent phosphatase calcineurin by FK506 or cyclosporine A blocks CREB‐dependent...
MicroRNAs (miRs) regulate essentially all cellular processes, but few miRs are known to inhibit growth of precursor-B acute lymphoblastic leukemias (B-ALLs). We identified miR-509 via a human genome-wide gain-of-function screen for that the NALM6 B-ALL cell line. MiR-509-mediated inhibition was confirmed by 3 independent assays. Enforced expression inhibited 2 additional lines tested, not non-B-ALL leukemia lines. MiR-509-transduced cells had reduced numbers actively proliferating and...
Abstract Artemisinins are active against human leukemia cell lines and have low clinical toxicity in worldwide use as antimalarials. Because multiagent combination regimens necessary to cure fully evolved leukemias, we sought leverage our previous finding that artemisinin analogs synergize with kinase inhibitors, including sorafenib (SOR), by identifying additional synergistic antileukemic drugs toxicity. Screening of a targeted antineoplastic drug library revealed B-cell lymphoma 2 (BCL2)...
Abstract To gain insight into sialic acid biology and sialidase/neuraminidase (NEU) expression in mature human neutrophil (PMN)s, we studied NEU activity PMNs the HL60 promyelocytic leukemic cell line, changes that might occur undergoing apoptosis cells during their differentiation PMN-like cells. Mature contained expressed NEU2, but not NEU1, NEU1 chaperone, protective protein/cathepsin A(PPCA), NEU3, NEU4 proteins. In proapoptotic PMNs, NEU2 protein increased > 30.0-fold. Granulocyte...
Inactivation of Ataxia-telangiectasia mutated (ATM) gene results in an increased risk to develop cancer. We show that ATM deficiency diffuse large B-cell lymphoma (DLBCL) significantly induce mitochondrial deacetylase sirtuin-3 (SIRT3) activity, disrupted structure, decreased respiration, and compromised TCA flux compared with DLBCL cells expressing wild type (WT)-ATM. This corresponded enrichment glutamate receptor glutamine pathways deficient background WT-ATM cells. ATM-/- have apoptosis...
Abstract Astrocytes participate in signaling via Ca 2+ transients that spread from cell to across a multicellular syncytium. The effect, if any, of these waves on the transcription /cAMP‐regulatory element binding protein (CREB)‐dependent genes is not known. We report here that, unlike neurons, increasing intracellular cultured mouse cortical astrocytes failed activate CREB‐dependent transcription, even though CREB was phosphorylated at serine 133. In contrast, both phosphorylation and were...
Successful cell therapy requires cells to resist the hostile ischemic myocardium, be retained continue secreting cardioprotective growth factors/exosomes, and immunological host responses. Clinically relevant stem/progenitor in a rodent model of acute myocardial infarction (MI) demonstrated that neonatal cardiac mesenchymal stromal (nMSCs) provide most robust functional recovery. Transplanted nMSCs significantly increased number tissue reparative macrophages regulatory T-cells decreased...