Sigrid A. Langhans, PhD

Research Interests

Dr. Langhans’ lab aims at developing innovative approaches for the therapy of pediatric brain tumors with a special focus on medulloblastoma. Medulloblastoma is the most common brain cancer found in children. This cancer usually forms in the cerebellum, the part of the brain that controls movement, balance, and posture. Although the cure rates are improving, approximately one-third of patients with medulloblastoma remain incurable. In addition, current treatments such as surgical resection, radiotherapy, and chemotherapy, have serious side effects. Survivors suffer from long-term damage including deficits in IQ, memory, and language, impaired growth and increased risk of secondary cancers. Reducing the long-term side effects is a key aspect of cancer treatment in children and requires a molecular understanding of how medulloblastoma develops. Towards this goal the Langhans lab investigates fundamental molecular mechanisms of neuronal cell migration during cerebellar development and how growth and differentiation of neuronal precursors is regulated by epigenetic mechanisms. Understanding how these pathways are dysregulated in brain tumors will allow for the development of novel therapeutics for pediatric brain cancers.

In a second project the Langhans lab recently evaluated curcumin as a safer therapeutic for medulloblastoma with reduced side effects. Curcumin, derived from the plant Curcuma longa, is the major component of turmeric, a spice frequently used in Asian cooking. Because of its anti-inflammatory properties, curcumin’s medicinal value had been recognized for many centuries. More recently, curcumin has gained wide attention as a potent anti-cancer agent and in clinical trials has demonstrated effectiveness and safety, with no discernable side effects. The Langhans lab found that curcumin reduces tumor growth and increases survival in medulloblastoma mouse models suggesting that curcumin has the potential to be developed as a therapeutic for medulloblastoma without the severe side effects of current treatments. At present, studies in the lab aim at understanding the molecular mechanisms governing why curcumin preferentially kills tumor cells over normal cells. These studies will enable us to identify biomarkers to predict which patients may respond favorably to curcumin therapy.

The failure of treatment for brain tumors in many instances is not due to the lack of potency of the drugs, but instead due to the failure of these drugs to reach the brain. The blood-brain barrier protects the brain from potentially toxic substances in the blood but also impedes efficient drug delivery. In a collaborative study, the Langhans and Pochan lab, in the Department of Materials and Engineering at the University of Delaware, are now developing unique approaches for drug delivery to the brain in order to circumvent the blood-brain barrier. This should allow to transfer the basic findings  from the lab bench to the bedside and make a difference in the lives of children diagnosed with brain cancer.

Dr. Langhans is a Senior Research Scientist at the Nemours Center for Childhood Cancer Research (NCCCR) at the Alfred I. duPont Hospital for Children. She holds academic positions as Research Assistant Professor of Pediatrics at Thomas Jefferson University Medical College, as Adjunct Associate Professor in the Department of Materials Science and Engineering at the University of Delaware and as Affiliated Scientist in the Department of Biological Sciences at the University of Delaware. She is a member of the Kimmel Cancer Center at Thomas Jefferson University. Prior to joining the NCCCR she had completed post-doctoral studies at UCLA and was an Adjunct Assistant Professor in the Department of Pathology and Laboratory Medicine at UCLA.

Current Projects

  • Intracellular ion homeostasis dependent regulation of signaling pathways
  • Epigenetic changes in response to ionic imbalance in pediatric brain tumors
  • Nanotechnology approaches for direct drug delivery to brain tumors

Research Group

  • Seung Joon Lee, Ph.D. – Postdoctoral Fellow
  • Sung Koo Kang, Ph.D. – Postdoctoral Fellow
  • Sridevi Mony, B.S. – Graduate Student
  • Bruce Graves – Undergraduate Student

Selected Publications

  • Barwe S.P., Kim S., Rajasekaran S.A., Bowie J.U., and Rajasekaran A.K. (2007) Janus model of the Na,K-ATPase b-subunit transmembrane domain: Distinct faces mediate a/b assembly and b-b homo-oligomerization. J. Mol. Biol. 365:706-714.
  • Rajasekaran S.A., Barwe S.P., Gopal J., Ryazantsev S., Schneeberger E.E. and Rajasekaran A.K. (2007) Na,K-ATPase regulates tight junction permeability through occludin phosphorylation in pancreatic epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 292:G124-G133.
  • Seligson D., Rajasekaran S.A., Yu H., Liu X., Eeva M., Tze S., Ball W. Jr., Horvath S., deKernion J., and Rajasekaran A.K. (2008) Na,K-ATPase a1-subunit predicts survival in renal clear cell carcinoma. J. Urol. 179: 338-345.
  • Inge L.J., Rajasekaran S.A., Yoshimoto K., Mischel P.S., McBride W., Landaw E., and Rajasekaran A.K. (2008) Evidence for a potential tumor suppressor role for the Na,K-ATPase b1-subunit. Histol. Histopathol. 23: 459-467.
  • Rajasekaran S.A., Christiansen J.J., Schmid I., Oshima E., Ryazantsev S., Sakamoto K., Weinstein J., Rao N.P. and Rajasekaran A.K. (2008) Prostate specific membrane antigen associates with anaphase promoting complex and induces chromosomal instability. Mol. Cancer Ther. 7: 2142-2151. *with press release
  • Inge L.J., Rajasekaran S.A., Wolle D., Barwe S.P., Ryazantsev S., Ewing C.M. Isaacs W.B. and Rajasekaran A.K. (2008) a-catenin overrides Src-dependenent activation of b-catenin oncogenic signaling. Mol. Cancer Ther. 7: 1386-1397.
  • Rajasekaran A.K. and Rajasekaran S.A. (2008) Epithelial-mesenchymal transition. Manfred Schwab (Editor), Encyclopedia of Cancer, 2nd edition, Springer.
  • Rajasekaran S.A., Beyenbach K.W., and Rajasekaran A.K. (2008) Interactions of tight junctions with membrane channels and transporters. Biochim Biophys Acta 1778: 757-769.
  • Barwe S.P., Jordan M.C., Skay A., Inge L., Rajasekaran S.A., Wolle D., Johnson C.L., Fan K., Rozengurt N., Golhaber J.I., Roos K.P. and Rajasekaran A.K. (2009) Dysfunction of ouabain-induced cardiac contractility in mice with heart-specific ablation of Na,K-ATPase b1-subunit. J. Cell. Mol. Cardiol. 47: 552-560. * with press release
  • Rajasekaran S.A.* and Rajasekaran A.K. (2009) Na,K-ATPase and epithelial tight junctions. Front. Biosci. 14: 2130-2148. *corresponding author
  • Vivanco I., Rohle D., Versele M., Iwanami A., Kuga D., Oldrini B., Dang J., Kubek S., Palaskas N., Hsueh T., Evans M., Mulholland D., Wolle D., Rajasekaran S., Rajasekaran A., Liau L., Cloughesy T., Dikic I., Brennan C., Wu H., Mischel P., Perera T., Millinghoff, I. (2010)  The phosphatase and tensin homolog requlates epidermal growth factor receptor inihibitor response by targeting EGFR for degradation. Proc. Natl. Acad. Sci. 107: 6459-6464.
  • Rajasekaran S.A.*, Huynh T.P., Wolle D., Espineda C., Inge L., Skay An., Lassman C., Nicholas S.B., Harper J.F., Reeves A.E., Ahmed M.M., Leatherman J.M., Mullin J.M., Rajasekaran A.K. (2010) Na,K-ATPase subunits as markers for epithelial-mesenchymal transition in cancer and fibrosis. Mol. Cancer Ther. 9: 1515-1524.  *co-corresponding author, * with press release
  • Rajasekaran S.A. (2011) Therapeutic potential of curcumin in gastrointestinal diseases. World J. Gastrointest Pathophysiol 2: 1-14.
  • Inge L.J., Barwe S.P., D’Ambrosio J., Gopal J.,  Lu K., Ryazantsev S., Rajasekaran S.A., Rajasekaran A.K. (2011)  Soluble E-cadherin promotes cell survival by activating epidermal growth factor receptor. Exp. Cell Res. 317: 838-848.
  • Lee S.J., Krauthauser C., Maduskuie V., Fawcett P.T., Olson J.M., Rajasekaran S.A. (2011) Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo. BMC Cancer 11: 144 * with press release.
  • Altunbas A., Lee S.J., Rajasekaran S.A., Schneider J.P., Pochan D.J. (2011) Encapsulation of Curcumin in Self-Assembling Peptide Hydrogels as Injectable Drug Delivery Vehicles. Biomaterials 32: 5906-5914.
  • Lee S.J. and Langhans S.A. (2012) Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis. BMC Cancer 12: 44 * with press release.

Head, Cancer Epigenetics Laboratory
A.I. duPont Hospital for Children

Phone: (302) 651-6538

Fax: (302) 651-4827

Email: sigrid.langhans@nemours.org

Office: Cancer Epigenetics Laboratory

Address:
Cancer Epigenetics Laboratory
Rockland Center I - 261
Nemours Biomedical Research
A.I. duPont Hospital for Children
1701 Rockland Road
Wilmington, DE 19803

Education

  • B.S. - Universtity of Ulm (Germany)
  • Ph.D. - Cornell University