Dr. Arnold Kristof
Associate Professor - Department of Medicine, Division of Experimental Medicine
1. Regulation of Nuclear Transport, Gene Expression, and Cell Survival by Mammalian Target of Rapamycin (mTOR):
We recently discovered that a protein kinase, mammalian target of rapamycin (mTOR), forms a macromolecular complex that and regulates the nuclear import of transcriptional regulators in response to cytokines and nutrient restriction. I am currently using in vitro and murine models to study the components and molecular determinants of this mTOR nuclear import complex, and how it regulates the pulmonary innate immune response and lung injury.
2. Amino Acid Nutrition in Critical Illness:
The availability of essential amino acids controls cell metabolism, growth, and survival. We are currently investigating the effects of dietary amino acid restriction and supplementation on cell death and organ injury in cultured cells, mouse models of bacterial infection, and critically ill human subjects.
3. 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 tumour-forming cells (LAM cells) grow and metastasize to the lung. We are currently working with engineered stem cell models to better understand the ‘cell of origin’ in LAM, and how it adopts cancer-like properties. The intent is to devise ways to cure LAM or prevent its clinical progression.