I am in my fourth year of graduate work in the program and continue to focus on structural modifications in targeting sequences found in oncogenic proteins, like Ras. We are investigating how structural determinants in the C-terminus of GTPases contribute to the regulation of post-translational modifications that dictate subcellular trafficking.
Thesis
Proline isomerization in the Hras hypervariable region regulates acylation cycling
Research Interests
How isomerization of peptide bonds that contain proline residues impart critical biological signals to the activity of proteins, including how proteins are post-translationally modified by acyl chain moeities that dictate sub-cellular trafficking
Selected Publications
Mor A,
Wynne J,
Ahearn IM, Dustin M, Du G, Philips MR. Phospholipase D1 Regulates Lymphocyte Adhesion via Upregulation of Rap1 at the Plasma Membrane. Mol Cell Biol. 2009 Mar;Epub 2009 Mar 30. Cited in Pubmed; PMID 19332557. doi:
10.1128/MCB.00366-09.
Wright LP, Court H, Mor A,
Ahearn IM, Casey PJ, Philips MR. Topology of Mammalian Isoprenylcysteine Carboxyl Methyltransferase Determined in Live Cells with a Fluorescent Probe. Mol Cell Biol. 2009;Epub 2009 Jan 21. Cited in Pubmed; PMID 19158273. doi:
10.1128/MCB.01719-08.
Michaelson D, Abidi W, Guardavaccaro D, Zhou M, Ahearn I, Pagano M, Philips. Rac1 Accumulates in the Nucleus During the G2 Phase of the Cell Cycle and Promotes Cell Division. J Cell Biol. 2008 May 5;181(3):485-96. Epub 2008 Apr 28. Cited in Pubmed; PMID 18443222. PMCID: PMC2364699.
Quatela SE,
Sung PJ,
Ahearn IM,
Bivona TG, Philips, MR. Analysis of K-Ras phosphorylation, translocation, and induction of apoptosis. Methods Enzymol. 2008;439:87-102. Epub 2008 Mar 26. Cited in Pubmed; PMID 18374158. doi:
10.1016/S0076-6879(07)00407-7. PMCID: PMC2293097.
Bivona TG,
Quatela SE, Bodemann BO,
Ahearn IM, Soskis MJ, Mor A, Miura J, Wiener HH, Wright L, Saba SG, Yim D, Fein A, Pérez de Castro I, Li C, Thompson CB, Cox AD, Philips MR. PKC regulates a farnesyl-electrostatic switch on K-Ras that promotes its association with Bcl-XL on mitochondria and induces apoptosis. Mol Cell. 2006 Feb 17;21(4):481-93. Cited in Pubmed; PMID 16483930. doi:
10.1016/j.molcel.2006.01.012.
Bivona TG, Wiener HH,
Ahearn IM, Silletti J,
Chiu VK, Philips MR. Rap1 up-regulation and activation on plasma membrane regulates T cell adhesion. J Cell Biol. 2004 Feb 2;164(3):461-70. Cited in Pubmed; PMID 14757755. doi:
10.1083/jcb.200311093.
Bivona TG, Pérez De Castro I,
Ahearn IM, Grana TM, Chiu VK, Lockyer PJ, Cullen PJ, Pellicer A, Cox AD, Philips MR. Phospholipase Cgamma activates Ras on the Golgi apparatus by means of RasGRP1. Nature. 2003 Aug 7;424(6949):694-8. Epub 2003 Jun 29. Cited in Pubmed; PMID 12845332. doi:
10.1038/nature01806.
Michaelson D, Ahearn I, Bergo M, Young S, Philips M. Membrane trafficking of heterotrimeric G proteins via the endoplasmic reticulum and Golgi. Mol Biol Cell. 2002 Sep;13(9):3294-302. Cited in Pubmed; PMID 12221133.
Ranganathan V, Heine WF, Ciccone DN, Rudolph KL, Wu X, Chang S, Hai H, Ahearn IM, Livingston DM, Resnick I, Rosen F, Seemanova E, Jarolim P, DePinho RA, Weaver DT. Rescue of a telomere length defect of Nijmegen breakage syndrome cells requires NBS and telomerase catalytic subunit. Curr Biol. 2001 Jun 26;11(12):962-6. Cited in Pubmed; PMID 11448772.
Additional Information
Philips Lab
