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    Sigrid Langhans, PhD

    Principal Research Scientist

    91´óÉñ 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 91´óÉñ High-Throughput Screening (HTS) & Drug Discovery Laboratory at 91´óÉñ 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 91´óÉñ 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 91´óÉñ PET Imaging Center, a clinically translatable PET imaging approach for pediatric brain tumors. Her research is supported by the 91´óÉñ Foundation, American Cancer Society, National Institutes of Health, and the D.O. Believe Foundation.

    Education

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

    • Tryptophan Kynurenine Pathway-Based Imaging Agents for Brain Disorders and Oncology—From Bench to Bedside; Biomolecules; (2025).

    • YAP/TAZ-associated cell signaling – at the crossroads of cancer and neurodevelopmental disorders; Frontiers in Cell and Developmental Biology; (2025).

    • Radiotracers for Molecular Imaging of Angiotensin-Converting Enzyme 2; International Journal of Molecular Sciences; (2024).

    • PET Imaging of Neurofibromatosis Type 1 with a Fluorine-18 Labeled Tryptophan Radiotracer; Pharmaceuticals; (2024).

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

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

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

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

    • Radiosynthesis of 1-(2-[18f]fluoroethyl)-l-tryptophan using a one-pot, two-step protocol; Journal of Visualized Experiments; (2021).

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

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

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

    • A Functional Interaction Between Na,K-ATPase β<sub>2</sub>-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).

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

    • Three-dimensional in vitro cell culture models in drug discovery and drug repositioning; Frontiers in Pharmacology; (2018).

    • β-hairpin peptide hydrogels for package delivery; Advanced Drug Delivery Reviews; (2017).

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

    • Epidermal growth factor signaling in transformed cells; International Review of Cell and Molecular Biology; (2015).

    • Peptide hydrogels - versatile matrices for 3D cell culture in cancer medicine; Frontiers in Oncology; (2015).

    • Na,K-ATPase β<sub>1</sub>-subunit is a target of sonic hedgehog signaling and enhances medulloblastoma tumorigenicity; Molecular Cancer; (2015).

    • Cancer as a channelopathy: Ion channels and pumps in tumor development and progression; Frontiers in Cellular Neuroscience; (2015).

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

    • Beta hairpin peptide hydrogels as an injectable solid vehicle for neurotrophic growth factor delivery; Biomacromolecules; (2015).

    • Crosstalk of oncogenic signaling pathways during epithelial-mesenchymal transition; Frontiers in Oncology; (2014).

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

    • Regulation of Na,K-ATPase β<sub>1</sub>-subunit in TGF-β<sub>2</sub>-mediated epithelial-to-mesenchymal transition in human retinal pigmented epithelial cells; Experimental Eye Research; (2013).

    • Sonic Hedgehog-Induced Histone Deacetylase Activation Is Required for Cerebellar Granule Precursor Hyperplasia in Medulloblastoma; PLoS ONE; (2013).

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

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

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

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

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

    • Encapsulation of curcumin in self-assembling peptide hydrogels as injectable drug delivery vehicles; Biomaterials; (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 β<sub>1</sub>-subunit; Journal of Molecular and Cellular Cardiology; (2009).

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

    • α-Catenin overrides Src-dependent activation of β-catenin oncogenic signaling; Molecular Cancer Therapeutics; (2008).

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

    • Evidence for a potential tumor suppressor role for the Na,K-ATPase ß<sub>1</sub>-subunit; Histology and Histopathology; (2008).

    • Interactions of tight junctions with membrane channels and transporters; Biochimica et Biophysica Acta - Biomembranes; (2008).

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

    • Prostate-specific membrane antigen associates with anaphase-promoting complex and induces chromosomal instability (Molecular Cancer Therapeutics (2008) 7, (2142-2151)); Molecular Cancer Therapeutics; (2008).

    • Na,K-Adenosine Triphosphatase α<sub>1</sub>-Subunit Predicts Survival of Renal Clear Cell Carcinoma; Journal of Urology; (2008).

    • Na-K-ATPase regulates tight junction permeability through occludin phosphorylation in pancreatic epithelial cells; American Journal of Physiology - Gastrointestinal and Liver Physiology; (2007).

    • Janus Model of The Na,K-ATPase β-Subunit Transmembrane Domain: Distinct Faces Mediate α/β Assembly and β-β Homo-oligomerization; Journal of Molecular Biology; (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).

    • Estrogen receptor-α binds p53 tumor suppressor protein directly and represses its function; Journal of Biological Chemistry; (2006).

    • Identification of protein kinase C as an intermediate in NA, K-atpase beta-subunit mediated lamellipodia formation and suppression of cell motility in carcinoma cells; Cellular and Molecular Biology; (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).

    • Novel role for Na,K-ATPase in phosphatidylinositol 3-kinase signaling and suppression of cell motility; Molecular Biology of the Cell; (2005).

    • Renal clear-cell carcinoma: An ultrastructural study on the junctional complexes; Histology and Histopathology; (2005).

    • Repression of Na,K-ATPase β<sub>1</sub>-Subunit by the Transcription Factor Snail in Carcinoma; Molecular Biology of the Cell; (2004).

    • Na,K-ATPase β<sub>1</sub>-subunit increases the translation efficiency of the α<sub>1</sub>-subunit in MSV-MDCK cells; Molecular Biology of the Cell; (2004).

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

    • 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).

    • A Novel Cytoplasmic Tail MXXXL Motif Mediates the Internalization of Prostate-specific Membrane Antigen; Molecular Biology of the Cell; (2003).

    • Expression of Na,K-ATPase β-subunit in transformed MDCK cells increases the translation of the Na,K-ATPase α-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).

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

    • Prostate-specific membrane antigen association with filamin A modulates its internalization and NAALADase activity; Cancer Research; (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 β-subunit is required for epithelial polarization, suppression of invasion, and cell motility; Molecular Biology of the Cell; (2001).

    • Reduced expression of β-subunit of NA,K-ATPase in human clear-cell renal cell carcinoma; Journal of Urology; (1999).

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

    • Only the first and the last hydrophobic segments in the COOH-terminal third of Na,K-ATPase α subunit initiate and halt, respectively, membrane translocation of the newly synthesized polypeptide: Implications for the membrane topology; Journal of Biological Chemistry; (1996).

    • A simple biochemical approach to quantitate rough endoplasmic reticulum; American Journal of Physiology - Cell Physiology; (1995).

    • Activation of Tsk and Btk tyrosine kinases by G protein βγ subunits; Proceedings of the National Academy of Sciences of the United States of America; (1995).