Jean Lord-Garcia

Current Position:

Toxicologist Additives Team, Toxicology and Health Risk Assessment, Chevron Energy Technology Company, Richmond, CA

Education:

• Ph.D. Pharmacology and Toxicology University of Arizona 2003-2008
• M.B.A., Project Management, Graduate School of Management, San Diego, CA 2002
• M.S.P.H., Toxicology, San Diego State University, Graduate School of Public Health, San Diego, CA 2002
• B.A., Liberal Arts and Sciences, Arizona State University, Tempe, AZ 1999

Achievements

• Graduate student travel award recipient, ASPET, Experimental Biology meeting, San Diego, CA 2005
• Finalist and Honorable Mentions of best student presentation at the Annual Mechanisms Specialty Section Carl C. Smith Graduate Student Award for Meritorious Research in Mechanisms of Toxicology Society of Toxicology, New Orleans, LA 2005
• NIEHS Toxicology and Toxicogenomics Training Program Predoctoral Trainee 2003-2004

Professional Experience:

• Research Assistant, University of Arizona, Tucson, AZ 2002-2008
• Research Associate II, VitaGen Inc., La Jolla, CA 2000-2002
• Graduate Teaching Assistant, San Diego State University, San Diego, CA 2000-2002
• Research Assistant, Agouron Pharmaceuticals, La Jolla, CA 1999-2000

Research Project:

Certain chemicals, such as hydroquinone, undergo glutathione conjugation in the liver and further metabolism in the kidney producing potent metabolites, which are selectively toxic to the renal proximal tubular epithelium. Ongoing research consists of investigating prostanoid mediated cytoprotective mechanisms in the kidney utilizing 2,3,5-tris-(glutathion-S-yl)hydroquinone (TGHQ) as a model compound of nephrotoxicity. 11-Deoxy-16,16-dimethyl prostaglandin E2 (DDM-PGE2) protects renal proximal tubular epithelial cells (LLC-PK1) against oncotic cell death, but not apoptotic cell death. Previous data shows that cytoprotection is associated with the up-regulation of at least five proteins, including glucose regulated protein 78 (Grp78) and several cytoskeletal proteins. 2D gel electrophoresis coupled with MALDI-TOF peptide mass mapping, we revealed that heat shock protein 27 (Hsp27) and retinol binding protein (RBP), are also selectively induced by DDM-PGE2.

My hypothesis was that DDM-PGE2 mediated cytoprotection involves stabilization of the actin cytoskeleton. The actin cytoskeleton is essential for the maintenance of cell integrity and for normal cellular functions and is one of the most sensitive, and earliest targets of oxidative stress. DDM-PGE2 selectively induces actin and several other cytoskeleton-related proteins, which likely helps to maintain cytoskeletal integrity during stress. Hsp27 plays an important role in regulating the stabilization of the actin network. More specifically, TGHQ induces Hsp27 phosphorylation only cells with a functional ER stress response. Grp78, the major resident ER chaperone is required for both the induction and phosphorylation of Hsp27. I utilized confocal microscopy to investigate the effects of DDM-PGE2 on cytoskeletal organization and the association of Hsp27 and Grp78 in this protection.

I was also interested in RBPs role in cytoprotection. The retinoic acid nuclear receptor (RAR) agonist, all-trans retinoic acid (ATRA), induced RBP with similar kinetics as DDM-PGE2. Treatment of ATRA also recapitulated the cytoprotective effects of DDM-PGE2 in LLC-PK1 cells, suggesting the possible involvement of retinoid signaling in the cytoprotection.

Finally, I investigated DDM-PGE2 ability to protect against TGHQ-induced renal necrosis in vivo by mechanisms identified in the in vitro model. It has been suggested that PG-mediated protection of the kidney in vivo involves regulation of renal hemodynamics, direct cellular actions, or a combination of both. Conclusions made from these investigations may contribute to future design of kidney disease therapeutics.

Publications:

Abstracts:

• All-Trans-Retinoic Acid Protects Against ROS Induced Kidney Injury. Lau, S.S., Lord-Garcia, J.L., Lai, L-W., Yong, K.Y., Lien, Y-H.H., and Monks, T.J. Toxicologist, 105, 906, 2011.

• Site specific phosphorylation of heat shock protein 27 (hsp27) regulates cell survival and death. Lord-Garcia, J., Labenski, M.T., Cromey, D., Xie, R., Galligan, M., Monks, T.J. and Lau, S.S. The FASEB Journal, 22, 1140.7, 2008.

• Renal toxicant-specific heat shock protein 27 phosphorylation. Lord J.L., Jia Z., Person, M.D., Shen J, Hunt A, Monks T.J., and Lau S.S.  The FASEB Journal, 20, Abstract #80.13, 2006.

• Chemical dependent phosphorylation of heat shock protein 27.  Lord, J.L., Jia, Z, Person, M.D., Shen J, Hunt A, Monks T.J., and Lau S.S. Toxicologist, 90, 483, 2006.

• Thromboxane receptor dependent induction of retinol binding protein contributes to 11-deoxy-16,16-dimethyl prostaglandin E2 mediated cytoprotection. Lord, J.L., Jia Z., Bratton, S.B., Monks, T.J. and Lau, S.S. The FASEB Journal, 19, Abstract #638.8, 2005.

• Up-regulation of heat shock protein 27 and retinol binding protein contributes to 11-deoxy-16,16-dimethyl prostaglandin E2 mediated cytoprotection. Lord, J.L., Jia, Z., Cromey, D.W., Lantz, R.C., Monks, T.J. and Lau, S.S. Toxicologist 84, 434, 2005.