mTOR • nutrition • acute lung injury • tuberous sclerosis complex • lymphangioleiomyomatosis
My research focuses on a protein enzyme in cells called ‘mammalian target of rapamycin', also known as mTOR. This protein senses growth factors and nutrients, and uses this information to tell the cell to grow, divide, and survive. When too active, mTOR contributes to cancer. When nutrients or growth factors are too low, reduced mTOR activity causes a ‘stress response' that favours cell death. We study how excessive mTOR suppresses cell death, and how this contributes to a cancer-like lung disease called lymphangioleiomyomatosis (LAM). On the flip side, we study why reduced mTOR activity amplifies cell death, lung inflammation, and lung injury. Studies are aimed at developing better molecular diagnostic and therapeutic approaches for patients with acute lung injury or LAM.
A.S. Kristof. mTOR Signaling in Lymphangioleiomyomatosis. Lymph. Res. Biol. 8(1): 33-42, 2010. PMID: 20235885.
J.A. Fielhaber, J. Tan, K.B. Joung, O. Attias, S. Huegel, M. Bader, P.P. Roux, A.S. Kristof. Regulation of Karyopherin a1 and Nuclear Import by mTOR. J. Biol. Chem. 287(18): 14325-14335, 2012. PMID: 22399302.
J.A. Fielhaber, S. Carroll, A. Bondo-Dydensborg, M. Shourian, A. Triantafillopolous, S. Harel, S.N. Hussain, M. Bouchard, S.T. Qureshi, A.S. Kristof. Inhibition of Mammalian Target of Rapamycin Augments Lipopolysaccharide-induced Lung Injury and Apoptosis. J. Immunol. 188(9): 4535-4542, 2012. PMID: 22450807.
J.A. Fielhaber, Y.S. Han, J. Tan, S. Xing, C.M. Biggs, K.B. Joung, and A.S. Kristof. Inactivation of Mammalian Target of Rapamycin Increases STAT1 Nuclear Content and Transcriptional Activity in Alpha4 and Protein Phosphatase 2A-dependent Fashion. J. Biol. Chem. 284(36): 24341-24353, 2009. PMID: 19553685.
K. Fredriksson, J.A. Fielhaber, J. Lam, X. Yao, K.S. Meyer, K.J. Keeran, G.J. Zywicke, X. Qu, Z. Yu, J. Moss, A.S. Kristof, S.J. Levine. Paradoxical Effects of Rapamycin on Experimental House Dust Mite-induced Asthma. PLoS One. 7(5): e33984. PMID: 22685525.