Arnold Kristof

Position
Associate Professor, Department of Medicine, McGill University

Currently accepting graduate students & postdoctoral fellows

Research Interests

1. Regulation of Nuclear Transport, Gene Expression, and Cell Survival by Mammalian Target of Rapamycin (mTOR):

We recently characterized a protein complex containing mammalian target of rapamycin (mTOR) and the transcription factor STAT1. mTOR, an essential amino acids sensor, regulates the nuclear import and pro-apoptotic transcriptional activity of STAT1. Using in vitro and murine models, we study how mTOR responds to nutrient restriction by controlling specific nuclear import adapters, which then drive transcriptional programs for cellular apoptosis and acute lung injury. In addition, we are conducting phase II clinical trials to determine whether protein supplementation can reverse catabolism in critically ill patients, and whether we can leverage multi-omics analyses to develop biomarkers of nutrition.

2. Control of cell survival and metastasis in lymphangioleiomyomatosis (LAM):

Loss of the TSC2 gene and increased mTOR activity plays an important role in LAM. I study mechanisms by which the abnormal cells (LAM cells) that cause LAM tumours in the lung grow and metastasize. We are currently working with induced pluripotent stem cells to better understand the ‘cell of origin’ in LAM, and how it adopts cancer-like properties. Our current projects focus on the mechanisms by which loss of TSC2 causes oncogenic G-protein coupled receptor signaling. The intent is to better understand how to cure LAM or prevent its clinical progression, and to develop novel therapies for this devastating disease.

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