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Sandra B. Gabelli, PhD

Department Affiliations Medicine, Oncology, Biophysics and Biophysical Chemistry
Rank Assistant Professor
Office Phone 410-614-4145
Lab Phone 410-955-8715
Fax 410-955-0637
Email gabelli@jhmi.edu
SOM Address 608c WBSB
Website

Gabelli Lab Page

Students

Research Interests

My research is aimed at elucidating the molecular mechanism of proteins involved in cell signaling pathways modulated by the second messenger phosphatidylinositol 3,4,5 triphosphate, (PIP3). To achieve a comprehensive understanding I am studying cytoplasmic protein-protein interactions involved in regulation of pathways such as PI3K and Na transporters. Many of these pathways are deregulated in diseases such as diarrhea, diabetes, inflammation and cancer. I seek to understand the structural basis of deregulation as a lead to design inhibitors for targeted therapies. My research integrates structural biology and chemical biology and it is focused on drug discovery. I am using biochemical and biophysical techniques including X-ray crystallography, SAXS, ITC, Mass spectrometry, AUC.

Publications

Research Profile

  • Mandelker D, Gabelli SB*, Schmidt-Kittler O, Zhu J, Cheong I, Huang CH, Kinzler KW, Vogelstein B, Amzel LM. A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane. Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):16996-7001. Epub 2009 Sep 23. PMID: 19805105; PMCID: PMC2761334.
  • Gabelli SB, Mandelker D, Schmidt-Kittler O, Vogelstein B, Amzel LM. Somatic mutations in PI3Kalpha: Structural basis for enzyme activation and drug design. Biochim Biophys Acta. 2010 Mar;1804(3):533-40. Epub 2009 Dec 2. Review. PMID: 19962457; PMCID: PMC2821964
  • Gabelli SB, Huang CH, Mandelker D, Schmidt-Kittler O, Vogelstein B, Amzel LM Structural Effects of Oncogenic PI3Kalpha Mutations. Curr Top Microbiol Immunol. 2010;347:43-53
  • Mohan S, Tse CM, Gabelli SB, Sarker R, Cha B, Fahie K, Nadella M, Zachos NC, Tu-Sekine B, Raben D, Amzel LM, Donowitz M. NHE3 activity is dependent on direct phosphoinositide binding at the N-terminus of its intracellular cytosolic region. J Biol Chem. 2010 Nov 5;285(45):34566-78. Epub 2010 Aug 24. PMID: 20736165; PMCID: PMC2966072.
  • Aripirala S, Szajnman SH, Jakoncic J, Rodriguez JB, Docampo R, Gabelli SB*, Amzel LM. Design, Synthesis, Calorimetry and Crystallographic analysis of 2-Alkylaminoethyl-1,1-Bisphosphonates as inhibitors of Trypanosoma cruzi Farnesyl Diphosphate Synthase. J Med Chem. 2012 Jun 20. PMID:22715997.
  • Bolduc DM, Rahdar M, Tu-Sekine B, Sivakumarin SC, Raben DM, Amzel LM, Devreotes PN, Gabelli SB* and Cole PA. (2013). Phosphorylation-mediated PTEN conformational closure and deactivation revealed by protein semisynthesis. eLIFE. 2013 Jul 9;2:e00691. doi: 10.7554/eLife.00691. Print 2013.
  • Miller MS, Schmidt-Kittler O, Bolduc DM, Brower ET, Chaves-Moreira D, Allaire M, Kinzler KW, Jennings IG, Thompson PE, Cole PA, Amzel LM, Vogelstein B, Gabelli SB*. Structural basis of nSH2 regulation and lipid binding in PI3Kα. Oncotarget. 2014 Jul 30;5(14):5198-5208.PMID:25105564

* Denotes senior and co-corresponding author