Sonali Barwe, Ph.D.

Research Interests

Mouse models in which human leukemic cells are transplanted in immuno-deficient mice can recapitulate the human disease such that human leukemic cells are detectable in the blood, bone marrow and spleen of the mouse. We continue to generate more mouse models using cells from patients treated at Nemours, and banked by the Nemours Tissue Procurement Laboratory. These mice are available for testing the efficacy of novel drugs on leukemia progression.

We also use this xenograft mouse model for understanding the molecular mechanisms of drug resistance and relapse, a great stumbling block in treatment of leukemia. The adhesion between hematopoietic stem cells and cells of the bone marrow is mediated by interactions between certain calcium binding proteins. Thus, disruption of these protein-protein interactions should have adverse effects on leukemia genesis and progression. Leukemic cells from patients that suffered relapse had higher levels of these proteins, suggesting that these proteins could also be used as predictive biomarkers for stratifying patients into high-risk or low-risk categories. Furthermore, understanding the cell signaling pathways induced by these proteins will help identify novel therapeutic targets.

Current Projects

  • Role of calcium-binding proteins in pediatric acute lymphoblastic leukemia relapse.
  • Developing novel drugs for pediatric leukemia using pre-clinical xenograft mouse models.
  • Understanding the molecular mechanism of drug resistance in pediatric leukemia.
  • Moonlighting role of β1-subunit of Na,K-ATPase in the regulation of Sodium/Calcium exchanger function.

Research Group

  • Anilkumar Gopala, Research Associate
  • Sonalakshme Balasubramaniam, Graduate Student
  • Anthony Quagliano, Masters Student

Selected Publications

  • Gopalakrishnapillai A, Kolb EA, Dhanan P, Mason RW, Napper A, Barwe SP. Disruption of annexin II/p11 interaction suppresses leukemia cell binding, homing and engraftment, and sensitizes leukemia cells to chemotherapy. PLOS One, October, 10(10):e0140564 (2015).
  • Lee SJ, Litan A, Li Z, Graves B, Lindsey S, Barwe SP, Langhans SA. Na,K-ATPase β1-subunit is a target of sonic hedgehog signaling and enhances medulloblastoma tumorigenicity. Mol. Cancer, August, 19(14): 159 (2015).
  • Balasubramaniam SL, Gopalakrishnapillai A, Barwe SP. Ion-dependency of Na,K-ATPase mediated epithelial cell adhesion and migration. Am J Physiol Cell Physiol, September, 309(6):C437-441 (2015).
  • Balasubramaniam SL, Gopalakrishnapillai A, Gangadharan V, Duncan RL, Barwe SP. Sodium-calcium exchanger 1 regulates epithelial cell migration via calcium-dependent extracellular signal-regulated kinase signaling. J Biol Chem, May, 290(20): 12463-12473 (2015).
  • Huynh TP, Barwe SP, Lee SJ, McSpadden R,Franco OE, Hayward S, Damoiseuax R, Rajasekaran AK. Glucocorticoids suppress renal cell carcinoma progression by enhancing Na,K-ATPase beta1-subunit expression. PLOS One, April, 10(4):e0122442 (2015).
  • Wolle D, Lee SJ, Barwe SP, Langhans SA. Inhibition of epidermal growth factor signaling by the cardiac glycoside ouabain in medulloblastoma. Cancer Med, October 3(5):1146-1158 (2014).
  • David JM, Owens TA, Barwe SP, Rajasekaran AK. Gramicidin A induces metabolic dysfunction and energy depletion leading to cell death in renal cell carcinoma cells. Mol Cancer Ther, November 12(11):p2296-2307 (2013).
  • Mony S, Lee SJ, Harper JF, Barwe SP, Langhans SA. Regualation of Na,K-ATPase beta1-subunit in TGF beta2-mediated epithelial-to-mesenchymal transition in human retinal pigmented epithelial cells. Exp Eye Res, October 115C:p113-122 (2013).
  • Krishnan V, Xu X, Barwe SP, Yang X, Czymmek, Witt RL, Waldman SA, Mason RW, Jia X, Rajasekaran AK. Dexamethasone-loaded block copolymer nanoparticles induce leukemia cell death and enhance therapeutic efficacy: a novel application in pediatric nanomedicine. Mol Pharm, June 10(6):p2199-2210 (2013).
  • Barwe SP, Skay A, McSpadden R, Inge L, Huynh T, Langhans, SA, Rajasekaran AK. Na,K-ATPase β-subunit cis homo-oligomerization is necessary for epithelial lumen formation in mammalian cells. J Cell Sci, December 125(23):p5711-5720 (2012).
  • Inge L, Barwe SP, D’Ambrosio J, Gopal J, Lu K, Ryazantsev S, Rajasekaran SA, Rajasekaran AK. Soluble E-cadherin promotes cell survival by activating epidermal growth factor receptor. Exp Cell Res, April, 3177 (6):p838-848 (2011).
  • Barwe SP, Jordan MC, Skay A, Inge L, Rajasekaran SA, Wolle D, Johnson CL, Neco P, Fang K, Rozengurt N, Goldhaber JI, Roos KP, Rajasekaran AK. Dysfunction of ouabain-induced cardiac contractility in mice with heart-specific ablation of Na,K-ATPase beta1-subunit. J Mol Cell Cardiol, October 47 (4): p552-560 (2009).
  • Tummala R, Wolle D, Barwe SP, Sampson, VB, Rajasekaran AK, Pendyala L. Expression Na,K-ATPase beta(1)-subunit increases uptake and sensitizes carcinoma cells to oxaliplatin. Cancer Chemother Pharmacol, November 64 (6): p1187-1194 (2009).
  • Inge L, Rajasekaran SA, Wolle D, Barwe SP, Ryazantsev S, Ewing CM, Isaacs WB, Rajasekaran AK. Alpha-catenin overrides Src-dependent activation of beta-catenin oncogenic signaling. Mol Cancer Ther, June, 7 (6):p1386-1397 (2008).
  • Goodman Jr OB, Barwe SP, McPherson P, Keen JH, Vasko A-J, Nanus DM, Bander NH, Rajasekaran AK. Interaction of prostate specific membrane antigen with clathrin and the adaptor-protein complex-2. Int J Onc, November 31 (5): p1199-1203 (2007).
  • Barwe SP, Maul RS, Anilkumar G, Kooper CR, Kohn DB, Rajasekaran AK. Preferential association of prostate specific membrane antigen expressing prostate cancer cells to bone marrow matrix. Int J Onc, April 30 (4): p899-904 (2007).
  • Rajasekaran SA, Barwe SP, Gopal J, Ryazantsev S, Schneeberger EE, Rajasekaran AK. Na,K-ATPase regulates tight junction permeability through occludin phosphorylation in pancreatic epithelial cells. Am J Physiol, Gastrointestinal and liver physiology, January 292: G124-133 (2007).
  • Barwe SP, Kim S, Rajasekaran SA, Bowie JU, Rajasekaran AK. Janus model of the Na,K-ATPase β-subunit transmembrane domain: Distinct faces mediate α/β subunit assembly and β-β homo-oligomerization. J Mol Biol, January 365 (3): p706-714 (2007).
  • Barwe SP, Rajasekaran SA, Rajasekaran AK. Identification of protein kinase C as an intermediate in Na,K-ATPase β-subunit mediated lamellipodia formation and suppression of cell motility in carcinoma cells. Cell Mol Biol, December 52 (8): p41-47 (2006).
  • Anilkumar G, Barwe SP#, Christiansen JJ, Rajasekaran SA, Kohn DB, Rajasekaran AK. Association of prostate-specific membrane antigen with caveolin-1 and its caveolae-dependent internalization in microvascular endothelial cells: Implications for targeting to tumor vasculature. Microvas Res, July-September 72 (1-2): p54-61 (2006). #Joint first author.
  • Rajasekaran SA, Barwe SP, Rajasekaran AK. Multiple functions of Na,K-ATPase in epithelial cells. Semin Nephrol, September, 25 (5): p328-334 (2005).
  • Barwe SP*, Anilkumar G, Moon SY, Zheng Y, Whitelegge J, Rajasekaran SA, Rajasekaran AK. Novel role for Na,K-ATPase in PI3-kinase signaling and suppression of cell motility. Mol Biol Cell, March (16): p1082-1094 (2005).
     

Research Scientist

Phone: (302) 651-6542

Fax: (302) 651-4827

Email: sonali.barwe@nemours.org

Office: Suite 260, Rockland One, Alfred I. duPont Hospital for Children

Address:
Nemours Biomedical Research, 
Alfred I. duPont Hospital for Children,
 1600 Rockland Road, 
Wilmington, DE 19803

Education

  • B.S. – University of Mumbai, India
  • M.S. - University of Mumbai, India
  • Ph.D. – Indian Institute of Science, India
  • Postdoctoral – University of California, Los Angeles