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    Sigrid Langhans, PhD

    Principal Research Scientist

    ÀÖ²¥´«Ã½ Children's Hospital, Delaware 1600 Rockland Road Wilmington, DE 19803

    Biography

    Sigrid A. Langhans, PhD, Principal Research Scientist, is Head of the Cancer Epigenetics Laboratory and Director of the ÀÖ²¥´«Ã½ High-Throughput Screening (HTS) & Drug Discovery Laboratory at ÀÖ²¥´«Ã½ Children's Health. Dr. Langhans is also an Affiliated Professor in the Department of Materials Science and Engineering at the University of Delaware, an affiliated faculty in the Department of Biological Sciences at the University of Delaware, and a Research Assistant Professor in the Department of Pediatrics at Thomas Jefferson University. Dr. Langhans earned her doctorate in physiology and biophysics from the Weill Medical College of Cornell University and was a post-doctoral fellow in tumor biology at the University of California, Los Angeles (UCLA). Her research focuses on molecular studies on signaling networks in cerebellar granule cell development and function and the relationship between neuronal development and cancer in the brain. Dr. Langhans' development of a comprehensive pediatric neuro-oncology research program at ÀÖ²¥´«Ã½ further encompasses collaborative research with the University of Delaware to develop a high-throughput screening (HTS)-compatible 3D cell culture platform for drug discovery, and together with the ÀÖ²¥´«Ã½ PET Imaging Center, a clinically translatable PET imaging approach for pediatric brain tumors. Her research is supported by the ÀÖ²¥´«Ã½ Foundation, American Cancer Society, National Institutes of Health, and the D.O. Believe Foundation.

    Medical/Dental School

    • PhD - Weill Cornell Graduate School of Medical Sciences, Physiology and Biophysics, 2001

    • Abusive Head Trauma Animal Models: Focus on Biomarkers; International Journal of Molecular Sciences; (2023).

    • 3D Hydrogel Cultures for High-Throughput Drug Discovery; Methods in molecular biology (Clifton, N.J.); (2023).

    • Advanced Neuroimaging Approaches to Pediatric Brain Tumors; Cancers; (2022).

    • Radiosynthesis of 1-(2-[<sup>18</sup>F]Fluoroethyl)-L-Tryptophan using a One-pot, Two-step Protocol; Journal of Visualized Experiments; (2021).

    • In Vivo and Ex Vivo Pediatric Brain Tumor Models: An Overview; Frontiers in Oncology; (2021).

    • Using 3D in vitro cell culture models in anti-cancer drug discovery; Expert Opinion on Drug Discovery; (2021).

    • Unravelling neuroinflammation in abusive head trauma with radiotracer imaging; Pediatric Radiology; (2021).

    • PET imaging of medulloblastoma with an 18F-labeled tryptophan analogue in a transgenic mouse model.; Scientific reports; (2020).

    • A Functional Interaction Between Na,K-ATPase β2-Subunit/AMOG and NF2/Merlin Regulates Growth Factor Signaling in Cerebellar Granule Cells; Molecular Neurobiology; (2019).

    • Implementation of a High-Throughput Pilot Screen in Peptide Hydrogel-Based Three-Dimensional Cell Cultures; SLAS Discovery; (2019).

    • Moving Myeloid Leukemia Drug Discovery Into the Third Dimension.; Frontiers in pediatrics; (2019).

    • Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning.; Frontiers in pharmacology; (2018).

    • RADI-17. EVALUATION OF A NOVEL F-LABELED TRYPTOPHAN TRACER FOR PET IMAGING OF BRAIN TUMORS IN A MEDULLOBLASTOMA MOUSE MODEL.; Neuro-oncology; (2018).

    • Beta-hairpin hydrogels as scaffolds for high-throughput drug discovery in three-dimensional cell culture.; Analytical biochemistry; (2017).

    • β-hairpin peptide hydrogels for package delivery.; Advanced drug delivery reviews; (2017).

    • Sustained release of active chemotherapeutics from injectable-solid β-hairpin peptide hydrogel.; Biomaterials science; (2016).

    • Transcriptional regulators of Na,K-ATPase subunits.; Frontiers in cell and developmental biology; (2015).

    • Cancer as a channelopathy: ion channels and pumps in tumor development and progression.; Frontiers in cellular neuroscience; (2015).

    • Beta Hairpin Peptide Hydrogels as an Injectable Solid Vehicle for Neurotrophic Growth Factor Delivery.; Biomacromolecules; (2015).

    • Na,K-ATPase β1-subunit is a target of sonic hedgehog signaling and enhances medulloblastoma tumorigenicity.; Molecular cancer; (2015).

    • Peptide Hydrogels - Versatile Matrices for 3D Cell Culture in Cancer Medicine.; Frontiers in oncology; (2015).

    • EGF-induced sodium influx regulates EGFR trafficking through HDAC6 and tubulin acetylation.; BMC cell biology; (2015).

    • Inhibition of epidermal growth factor signaling by the cardiac glycoside ouabain in medulloblastoma.; Cancer medicine; (2014).

    • Crosstalk of Oncogenic Signaling Pathways during Epithelial-Mesenchymal Transition.; Frontiers in oncology; (2014).

    • Epidermal growth factor signaling in transformed cells.; International review of cell and molecular biology; (2014).

    • Sonic hedgehog-induced histone deacetylase activation is required for cerebellar granule precursor hyperplasia in medulloblastoma.; PloS one; (2013).

    • Regulation of Na,K-ATPase β1-subunit in TGF-β2-mediated epithelial-to-mesenchymal transition in human retinal pigmented epithelial cells.; Experimental eye research; (2013).

    • Na,K-ATPase β-subunit cis homo-oligomerization is necessary for epithelial lumen formation in mammalian cells.; Journal of cell science; (2012).

    • Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis.; BMC cancer; (2012).

    • Na,K-ATPase is a target of cigarette smoke and reduced expression predicts poor patient outcome of smokers with lung cancer.; American journal of physiology. Lung cellular and molecular physiology; (2012).

    • Soluble E-cadherin promotes cell survival by activating epidermal growth factor receptor.; Experimental cell research; (2011).

    • Encapsulation of curcumin in self-assembling peptide hydrogels as injectable drug delivery vehicles.; Biomaterials; (2011).

    • Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo.; BMC cancer; (2011).

    • Therapeutic potential of curcumin in gastrointestinal diseases.; World journal of gastrointestinal pathophysiology; (2011).

    • Na,K-ATPase subunits as markers for epithelial-mesenchymal transition in cancer and fibrosis.; Molecular cancer therapeutics; (2010).

    • The phosphatase and tensin homolog regulates epidermal growth factor receptor (EGFR) inhibitor response by targeting EGFR for degradation.; Proceedings of the National Academy of Sciences of the United States of America; (2010).

    • Dysfunction of ouabain-induced cardiac contractility in mice with heart-specific ablation of Na,K-ATPase beta1-subunit.; Journal of molecular and cellular cardiology; (2009).

    • Na,K-ATPase and epithelial tight junctions.; Frontiers in bioscience (Landmark edition); (2009).

    • alpha-Catenin overrides Src-dependent activation of beta-catenin oncogenic signaling.; Molecular cancer therapeutics; (2008).

    • Prostate-specific membrane antigen associates with anaphase-promoting complex and induces chromosomal instability.; Molecular cancer therapeutics; (2008).

    • Evidence for a potential tumor suppressor role for the Na,K-ATPase beta1-subunit.; Histology and histopathology; (2008).

    • Interactions of tight junctions with membrane channels and transporters.; Biochimica et biophysica acta; (2007).

    • Na,K-adenosine triphosphatase alpha1-subunit predicts survival of renal clear cell carcinoma.; The Journal of urology; (2007).

    • Association of prostate-specific membrane antigen with caveolin-1 and its caveolae-dependent internalization in microvascular endothelial cells: implications for targeting to tumor vasculature.; Microvascular research; (2006).

    • Janus model of the Na,K-ATPase beta-subunit transmembrane domain: distinct faces mediate alpha/beta assembly and beta-beta homo-oligomerization.; Journal of molecular biology; (2006).

    • Na-K-ATPase regulates tight junction permeability through occludin phosphorylation in pancreatic epithelial cells.; American journal of physiology. Gastrointestinal and liver physiology; (2006).

    • Estrogen receptor-alpha binds p53 tumor suppressor protein directly and represses its function.; The Journal of biological chemistry; (2006).

    • Multiple functions of Na,K-ATPase in epithelial cells.; Seminars in nephrology; (2005).

    • N-glycosylation and microtubule integrity are involved in apical targeting of prostate-specific membrane antigen: implications for immunotherapy.; Molecular cancer therapeutics; (2005).

    • HPAF-II, a cell culture model to study pancreatic epithelial cell structure and function.; Pancreas; (2004).

    • Na,K-ATPase beta1-subunit increases the translation efficiency of the alpha1-subunit in MSV-MDCK cells.; Molecular biology of the cell; (2004).

    • Novel role for Na,K-ATPase in phosphatidylinositol 3-kinase signaling and suppression of cell motility.; Molecular biology of the cell; (2004).

    • Repression of Na,K-ATPase beta1-subunit by the transcription factor snail in carcinoma.; Molecular biology of the cell; (2003).

    • A novel cytoplasmic tail MXXXL motif mediates the internalization of prostate-specific membrane antigen.; Molecular biology of the cell; (2003).

    • Role of Na-K-ATPase in the assembly of tight junctions.; American journal of physiology. Renal physiology; (2003).

    • Prostate-specific membrane antigen association with filamin A modulates its internalization and NAALADase activity.; Cancer research; (2003).

    • Expression of Na,K-ATPase beta-subunit in transformed MDCK cells increases the translation of the Na,K-ATPase alpha-subunit.; Annals of the New York Academy of Sciences; (2003).

    • Na,K-ATPase in the regulation of epithelial cell structure.; Annals of the New York Academy of Sciences; (2003).

    • Polarity of prostate specific membrane antigen, prostate stem cell antigen, and prostate specific antigen in prostate tissue and in a cultured epithelial cell line.; The Prostate; (2003).

    • Na,K-ATPase inhibition alters tight junction structure and permeability in human retinal pigment epithelial cells.; American journal of physiology. Cell physiology; (2003).

    • Na,K-ATPase activity is required for formation of tight junctions, desmosomes, and induction of polarity in epithelial cells.; Molecular biology of the cell; (2001).

    • Na,K-ATPase beta-subunit is required for epithelial polarization, suppression of invasion, and cell motility.; Molecular biology of the cell; (2001).

    • Highly specific separation of heterogeneous cell populations by lectin-coated beads: application for the isolation of inner medullary collecting duct cells.; Experimental nephrology; (1998).