|Department Affiliations||Medicine, Oncology, Biophysics and Biophysical Chemistry|
|SOM Address||608c WBSB|
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.
- 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