Jack W. Olson, Ph.D.
||University of Southern California
||University of Arizona
General Research Area
Dr. Olson's laboratory focuses on the pathobiology of pulmonary arterial hypertension (PAH) and identifying targets for the therapy of human PAH. Human familial and idiopathic PAH are devastating, rapidly fatal angioproliferative diseases that obliterate the small arteries of the lung. This obliterative remodeling - due to the aberrant proliferative and antiapoptotic phenotypes of lung vascular cells - leads to increased vascular resistance, right heart failure and death.
- Determine whether polyamines are rationale targets for human PAH drug therapy. Polyamines (putrescine, spermidine and spermine) are essential for cell survival and proliferation. They regulate many functions including cell division, apoptosis, gene transcription and, synthesis of DNA, RNA and proteins.
- Determine the roles of microRNAs in PAH vascular remodeling processes.
- Use induced pluripotent stem cell technology as a platform to dissect the pathogenic mechanisms of PAH and develop cell-based therapy.
- Olson JW, Orlinska U, Gillespie MN. Polyamine synthesis blockade in monocrotaline-induced pneumotoxicity. Biochem Pharmacol 38: 2903-10, 1989.
- Shiao RT, Kostenbauder HB, Olson JW, Gillespie MN. Mechanisms of lung polyamine accumulation in chronic hypoxic pulmonary hypertension. Am J Physiol 259: L351-8, 1990.
- Aziz SM, Gosland MP, Crooks PA, Olson JW, Gillespie MN. A novel polymeric spermine conjugate inhibits polyamine transport in pulmonary artery smooth muscle cells. J Pharmacol Exp Ther 274: 181-6, 1995.
- Babal P, Manuel SM, Olson JW, Gillespie MN. Cellular disposition of transported polyamines in hypoxic rat lung and pulmonary arteries. Am J Physiol Lung Cell Mol Physiol 278: L610-7, 2000.
- Babal P, Ruchko M, Ault-Ziel K, Cronenberg L, Olson JW, Gillespie MN. Regulation of ornithine decarboxylase and polyamine import by hypoxia in pulmonary artery endothelial cellls. Am J Physiol Lung Cell Mol Physiol 282: L840-L846, 2002.
- Ruchko M, Gillespie MN, Weeks RS, Olson JW, Babal P. Putrescine transport in hypoxic rat main PASMCs is required for p38 MAP kinase activation. Am J Physiol Lung Cell Mol Physiol 284: L179-L186, 2003.
- Gillespie MN, Ziel KA, Ruchko M, Babál P, Olson JW. Polyamine regulation in hypoxic pulmonary arterial cells. In "Hypoxic pulmonary hypertension: Cell and Molecular Mechanisms" Ed: J X-J Yuan. Klewer Academic Publishers, 2004.
- Olson JW, Gillespie MN. Polyamines in pulmonary vascular biology. In "Polyamine Cell Signaling: Physiology, Pharmacology and Cancer Research. Eds: J-Y Wang and RA Casero, Jr. Humana Press, Inc. 2006.
- Chen R, Ruchko M, Gillespie MN, Olson JW. Ornithine decarboxylase promotes fibronectin splicing and expression during development of monocrotaline-induced pulmonary hypertension. In preparation.
- Zhang Y, Ruchko M, Olson JW. Increased ornithine decarboxylase activity contributes to monocrotaline-caused pulmonary artery endothelial cell apoptosis. In preparation.
- Zhang Y, Ruchko M, Comhair S, Erzurum S, Olson JW. Ornithine decarboxylase promotes the endothelial angioproliferative phenotype in human and rat pulmonary hypertension. In preparation.