Faculty Homepages
Mary K. Walker, PhD
Professor
Specialty: Pharmacology & Toxicology
Division of Pharmaceutical
Sciences
Office: Research Incubator Building, room 293
Phone: 505.272.0580
Scholarly Interests: The aryl hydrocarbon receptor (AHR) belongs to the basic-helix-loop-helix-PAS superfamily of transcription factors. Although the identity of an endogenous ligand for AHR is uncertain, environmental pollutants, such as the halogenated aromatic hydrocarbons, represent high affinity ligands. It is notable that both (a) sustained activation of AHR by these pollutants and (b) genetic deletion of AHR result in cardiovascular disease, suggesting that AHR functions to maintain physiological balance of the cardiovascular system. Dr. Walker’s research focuses on the mechanisms by which AHR, and a downstream transcriptional target gene, cytochrome P4501A1, contribute to the regulation of blood pressure and cardiac function under physiological and pathological conditions. Experimental approaches used in her laboratory include AHR and cytochrome P4501A1 null mice as well as mice in which these targets have been conditionally deleted in a cell-type specific manner. In addition, sustained activation of this pathway is achieved by xenobiotic activation of AHR and use of transgenic mice that conditionally over expression CYP1A1.
Selected Publications
Lund, A.K., M.B. Goens, N.L. Kanagy, and M.K. Walker. 2003. Cardiac hypertrophy in aryl hydrocarbon null (AhR) null mice is correlated with elevated angiotensin II, endothelin-1 and mean arterial blood pressure. Toxicol. Appl. Pharmacol.,193, 177-187.
Ivnitski-Steele, I.D., A. Sanchez, and M.K. Walker. 2004. 2,3,7,8-Tetrachlorodibenzo-p-dioxin reduces myocardial hypoxia and vascular endothelial growth factor expression during chick embryo development. Birth Defects Research: Clin. Mol.Teratol.,70, 51-58.
C.D. Johnson, Y. Balagurunathan, M.G. Tadesse, M.H. Falahatpisheh, M.K. Walker, E.R. Dougherty, K.S. Ramos. 2004. Unraveling gene-gene interactions regulated by ligands of the aryl hydrocarbon receptor. EHP Toxicogenomics, 112, 403-412.
Berwick, M., G. Matullo, Y.S. Song, S. Guarrera, G. Dominguez, I. Orlow, M.K. Walker, P. Vineis. 2004. Association between AhR genotype and survival in soft tissue sarcoma. J. Clin. Oncol., 22, 3997-4001.
Ivnitski-Steele, I.D., M. Chavez, M. Friggens, and M.K. Walker. 2005. 2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibits coronary vasculogenesis, in part, by reduced endothelial cell responsiveness to angiogenic stimuli, including vascular endothelial growth factor-A. Birth Defects Research: Clin. Mol. Teratol.,73, 440-446.
Lund, A.K., S. Peterson, G. Timmins, and M.K. Walker. 2005. Endothelin-1-mediated increase in reactive oxygen species and NADPH oxidase activity in heart of aryl hydrocarbon receptor null mice. Toxicol. Sci., 88, 265-273.
Thackaberry, E.A., Jiang, Z., Johnson, C.D., K.S. Ramos, and M.K. Walker. 2005. Toxicogenomic profile of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the fetal murine heart: Modulation of cell cycle and extracellular matrix genes. Toxicol. Sci, 88, 231-241.
Thackaberry, E.A., B.A. Nunez, I.D. Ivnitski-Steele, M. Friggens, and M.K. Walker. 2005. Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on murine heart development: Alteration in fetal and postnatal cardiac growth, and postnatal cardiac chronotropy. Toxicol. Sci, 88, 242-249.
Lund, A.K., M.B. Goens, B.A. Nunez, M.K. Walker. 2006. Characterizing the role of endothelin-1 in the progression of cardiac hypertrophy in aryl hydrocarbon receptor null mice. Toxicol. Appl. Pharmacol., 212, 127-135.
Zhang, N. and M.K. Walker. 2007. Crosstalk between the aryl
hydrocarbon receptor and hypoxia on the constitutive expression of
cytochrome P4501A1 mRNA. Cardiovas. Toxicol. 7, 282-290
Aragon, A.C., P.G. Kopf, J.K. Huwe, E.J. Bedrick, and M.K. Walker. 2008.
In utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure:
I. Effects on fetal and adult cardiac gene expression. Toxicol. Sci.
101, 321-330
Lund, A.K., L.N. Agbor, N. Zhang, A. Baker, H. Zhao, G.D. Fink, N.L.
Kanagy, and M.K. Walker. 2008. Loss of the aryl hydrocarbon receptor
induces hypoxemia, endothelin-1, and systemic hypertension at modest
altitude. Hypertension. 51, 803-809.
de Frutos, S., L. Duling, D. Alo, T. Berry, O. Jackson-Weaver, M.K.
Walker, N.L. Kanagy, and L.V. Gonzalez Bosc. 2008. NFATc3 is required
for intermittent hypoxia-induced hypertension. Am J Physiol Heart Circ
Physiol. Mar 21; [Epub ahead of print] PMID: 18359899
Aragon, A.C., M.B. Goens, E. Carbett, and M.K. Walker. 2008. Perinatal
2,3,7,8-tetrachlorodibenzo-p-dioxin exposure sensitizes offspring to
angiotensin II-induced hypertension. Cardiovasc. Toxicol., 8(3):145-54.
Kopf, P.G., J.K. Huwe, and M.K. Walker. 2008. Hypertension, Cardiac
Hypertrophy, and Impaired Vascular Relaxation induced by
2,3,7,8-Tetrachlorodibenzo-p-dioxin are Associated with Increased
Superoxide. Cardiovasc.Toxicol. 8(4):181-193. PMCID: PMC2648846
The
University of New Mexico’s Doctor of Pharmacy program is
accredited by the Accreditation Council for Pharmacy Education,
20 North Clark Street, Suite 2500, Chicago, IL 60602-5109, TEL
(312) 664-3575 , FAX (312) 664-4652,
URL
http://www.acpe-accredit.org/
05/11/2009 11:29:41 AM -0600.