Johana Vallejo-Elias, Ph.D.

Associate Professor


Johana Vallejo Portrait

Midwestern University
Arizona College of Osteopathic Medicine
Department of Physiology
Agave Hall, Room 217-J
19555 N. 59th Avenue
Glendale, AZ 85308

Office: 623.572.3313 / Fax: 623.572.3673 / Lab: 623.572.3487

Email

EDUCATION

B.S. Biology University of Puerto Rico, Cayey, Puerto Rico 1999
Ph.D. Physiology University of Missouri, Columbia, MO 2004

RESEARCH SUMMARY

The caveolins (caveolin-1, -2, and -3) are integral membrane proteins  that together with sphingolipids and cholesterol, make up cell membrane invaginations known as caveolae.  Caveolae serve as scaffolds to localize cellular signaling and in the regulation of cholesterol homeostasis. In our lab we study the role of caveolae in cellular signaling and metabolism within three disease models (see below).  

Project I: Caveolae and Marfan Syndrome: Marfan syndrome (MFS) is a connective tissue disorder that results from the degradation of elastic fibers. Elastic fiber degradation affects the ocular, skeletal, pulmonary, cutaneous, and cardiovascular systems in Marfan patients. Although, there are many clinical manifestations associated with MFS, the hallmark of the disease and leading cause of patient death is aortic aneurysm. The fibrillin-1 mutation characteristic of MFS results in elevated levels of circulating transforming growth factor beta (TGF-β) which leads to collagen and elastin fiber degradation and vascular smooth muscle cell (VSMC) proliferation. Angiotensin II type 1 receptor (AT1R) blockers (e.g. Losartan) have been shown to prevent and rescue the aortic pathology associated with MFS. Caveolin-1 (CAV-1) plays a regulatory role in the TGF-β and AT1R pathways. In addition, active AT1Rs are located within caveolae. Thus, we seek to investigate the role of CAV-1 in the regulation of TGF-β signaling in human aortic vascular smooth muscle cells (hASMCs) and in a mouse model of Marfan syndrome. This project is done in collaboration with Dr. Mitra Esfandiarei from the Biomedical Sciences Department.  

Project II: Caveolae and Alzheimer 's Disease: Alzheimer's disease (AD) is a neurodegenerative disease characterized by alterations of cholesterol homeostasis and metabolism in both the periphery and the central nervous system. The Apolipoprotein E allele 4 (APOE4) is a well-known risk factor for sporadic and familial late onset AD. Amyloid precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. APP is best known as the precursor molecule whose proteolysis generates beta amyloid (Aβ), which is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients. Caveolin-1 (CAV-1) has been implicated in the pathophysiology of AD by: (1) its interaction with proteins involved in the processing of APP and by (2) its association with APOE in adipocytes. However, there are no reports of an association between CAV1 and APOE in the brain or in AD. Thus, we seek to elucidate the role of caveolin expression in the cellular organization, interactions, and compartmentation of key proteins related to glucose uptake and metabolism in brain samples from APOE4 mice and from postmortem young adults APOE4 carriers.  This project is done in collaboration with Dr. Jon Valla and Dr. Garilyn Jentarra from the Biochemistry Department.  

Project III:  Caveolae and Insulin Resistance: The strongest risk factor for type 2 diabetes mellitus (T2DM) is central obesity, which leads to: (1) low-grade inflammation mediated by cytokines such as tumor necrosis factor alpha (TNFα), and (2) elevated levels of circulating free fatty acids (FFAs) from lipolysis. Different genes have been related to T2DM development, such as the caveolins. CAV-1 and CAV-3 proteins act as scaffolding domains for insulin receptor localization to the plasma membrane. Additionally, CAV-3 deficient mice develop late-onset obesity accompanied by insulin resistance and abnormal lipid metabolism. Thus, we seek to investigate the effect of TNFα and FFAs in insulin signaling, glucose uptake, and in the localization of the insulin signaling cascade to the caveolae plasma membrane domain in cell culture models of adipose tissue and skeletal muscle.

SELECTED PUBLICATIONS

Metabolic organization in vascular smooth muscle: distribution and localization of caveolin-1 and phosphofructokinase.
Vallejo J, Hardin CD.Am J Physiol Cell Physiol. 2004 Jan;286(1):C43-54. Epub 2003 Aug 27

Caveolin-1 functions as a scaffolding protein for phosphofructokinase in the metabolic organization of vascular smooth muscle.
Vallejo J, Hardin CD.Biochemistry. 2004 Dec 28;43(51):16224-32

Expression of caveolin-1 in lymphocytes induces caveolae formation and recruitment of phosphofructokinase to the plasma membrane.
Vallejo J, Hardin CD.FASEB J. 2005 Apr;19(6):586-7. Epub 2005 Jan 21.

Caveolins in vascular smooth muscle: form organizing function.
Hardin CD, Vallejo J.Cardiovasc Res. 2006 Mar 1;69(4):808-15. Epub 2006 Jan 4. Review

Overexpression of caveolin-1 results in increased plasma membrane targeting of glycolytic enzymes: the structural basis for a membrane associated metabolic compartment.
Raikar LS, Vallejo J, Lloyd PG, Hardin CD.J Cell Biochem. 2006 Jul 1;98(4):861-71

Dissecting the functions of protein-protein interactions: caveolin as a promiscuous partner. Focus on "Caveolin-1 scaffold domain interacts with TRPC1 and IP3R3 to regulate Ca2+ store release-induced Ca2+ entry in endothelial cells".
Hardin CD, Vallejo J.Am J Physiol Cell Physiol. 2009 Mar;296(3):C387-9. doi: 10.1152/ajpcell.00663.2008. Epub 2008 Dec 31.

Ketones prevent synaptic dysfunction induced by mitochondrial respiratory complex inhibitors.
Kim do Y, Vallejo J, Rho JM.J Neurochem. 2010 Jul;114(1):130-41. doi: 10.1111/j.1471-4159.2010.06728.x. Epub 2010 Apr 2.

Altered Energy Metabolism Pathways in the Posterior Cingulate in Young Adult Apolipoprotein E ɛ4 Carriers
Perkins, M., Wolf, A. B., Chavira, B., Shonebarger, D., Meckel, J. P., Leung, L., Balina, L., Ly, S., Saini, A., Jones, T.B., Vallejo, J., Jentarra, G. and Valla, J. (2016). Altered Energy Metabolism Pathways in the Posterior Cingulate in Young Adult Apolipoprotein E ɛ4 Carriers. Journal of Alzheimer's Disease53(1), 95-106. http://doi.org/10.3233/JAD-151205