Education and Training
I have been trained as a physiologist with a strong background in cellular signaling systems and application of optical techniques. The current proposed projects calls for both in vitro and in vivo imaging approaches, all areas requiring expertise that I already possess and have published in as first author. Critically, I have developed a novel approach that allows in vivo FRET imaging of the vasculature in mice (Mauban et al, AJP Heart Circ Physiol 2014). This unique capability allows our group to conduct acute and longitudinal measurements of Ca2+ in the mouse vasculature in vivo. The approach even allows the observation of an exact vascular branch through a period of time. My collaborators Drs. Wier and Rizzo, together, bring additional wealth of experience in vascular biology, Ca2+ imaging and biosensor development. The environment here at the University of Maryland is optimally suited for the proposed study as all equipment (widefield fluorescence, upright multiphoton confocal microscopes) are already available and members of the group are highly trained in their use.
Zacharia J, Mauban JR, Raina H, Fisher SA, Wier WG. High vascular tone of mouse femoral arteries in vivo is determined by sympathetic nerve activity via α1A- and α1D-adrenoceptor subtypes. PloS one. 2013; 8(6):e65969. PMCID: PMC3680395
Mauban JR, Zacharia J, Zhang J, Wier WG. Vascular tone and Ca(2+) signaling in murine cremaster muscle arterioles in vivo.Microcirculation (New York, N.Y. : 1994). 2013; 20(3):269-77. NIHMSID: NIHMS574799. PMCID: PMC4019383
Fairfax ST, Mauban JR, Hao S, Rizzo MA, Zhang J, et al. Ca(2+) signaling in arterioles and small arteries of conscious, restrained, optical biosensor mice. Frontiers in physiology. 2014; 5:387. PMCID: PMC4188025
Mauban JR, Fairfax ST, Rizzo MA, Zhang J, Wier WG. A method for noninvasive longitudinal measurements of [Ca2+] in arterioles of hypertensive optical biosensor mice. American journal of physiology. Heart and circulatory physiology. 2014; 307(2):H173-81. PMCID: PMC4101644
Mauban JR, Zacharia J, Fairfax S, Wier WG. PC-PLC/sphingomyelin synthase activity plays a central role in the development of myogenic tone in murine resistance arteries. American journal of physiology. Heart and circulatory physiology. 2015; 308(12):H1517-24. PMCID: PMC4469871
Miriel VA, Mauban JR, Blaustein MP, Wier WG. Local and cellular Ca2+ transients in smooth muscle of pressurized rat resistance arteries during myogenic and agonist stimulation. The Journal of physiology. 1999; 518 ( Pt 3):815-24. PMCID: PMC2269448
Wier WG, Balke CW, Michael JA, Mauban JR. A custom confocal and two-photon digital laser scanning microscope. American journal of physiology. Heart and circulatory physiology. 2000; 278(6):H2150-6. PMID: 10843915
Izu LT, Mauban JR, Balke CW, Wier WG. Large currents generate cardiac Ca2+ sparks. Biophysical journal. 2001; 80(1):88-102. PMCID: PMC1301216
Mauban JR, Lamont C, Balke CW, Wier WG. Adrenergic stimulation of rat resistance arteries affects Ca(2+) sparks, Ca(2+) waves, and Ca(2+) oscillations. American journal of physiology. Heart and circulatory physiology. 2001; 280(5):H2399-405. PMID: 11299247
Mauban JR, Wier WG. Essential role of EDHF in the initiation and maintenance of adrenergic vasomotion in rat mesenteric arteries. American journal of physiology. Heart and circulatory physiology. 2004; 287(2):H608-16. PMID: 15059779
Mauban JR, Remillard CV, Yuan JX. Hypoxic pulmonary vasoconstriction: role of ion channels. Journal of applied physiology(Bethesda, Md. : 1985). 2005; 98(1):415-20. PMID: 15591311
Mauban JR, Wilkinson K, Schach C, Yuan JX. Histamine-mediated increases in cytosolic [Ca2+] involve different mechanisms in human pulmonary artery smooth muscle and endothelial cells. American journal of physiology. Cell physiology. 2006; 290(2):C325-36. NIHMSID: NIHMS5082. PMCID: PMC1351365
Manni S, Mauban JR, Ward CW, Bond M. Phosphorylation of the cAMP-dependent protein kinase (PKA) regulatory subunit modulates PKA-AKAP interaction, substrate phosphorylation, and calcium signaling in cardiac cells. The Journal of biological chemistry. 2008; 283(35):24145-54. PMCID: PMC2527120
Mauban JR, O'Donnell M, Warrier S, Manni S, Bond M. AKAP-scaffolding proteins and regulation of cardiac physiology. Physiology(Bethesda, Md.). 2009; 24:78-87. NIHMSID: NIHMS131868. PMCID: PMC2751630
Zhang J, Hamlyn JM, Karashima E, Raina H, Mauban JR, et al. Low-dose ouabain constricts small arteries from ouabain-hypertensive rats: implications for sustained elevation of vascular resistance. American journal of physiology. Heart and circulatory physiology. 2009; 297(3):H1140-50. PMCID: PMC2755988
Shanks MO, Lund LM, Manni S, Russell M, Mauban JR, et al. Chromodomain helicase binding protein 8 (Chd8) is a novel A-kinase anchoring protein expressed during rat cardiac development. PloS one. 2012; 7(10):e46316. PMCID: PMC3468582
Confocal FRET imaging in vivo presents a multitude of challenges for investigators. Proper physical restraint of the living animal to enable negation of movement and breathing artifacts are paramount to successful experimentation. I have developed the necessary methodologies that make in vivo imaging in mice a routine and easy process. With this approach we can make acute and longitudinal FRET measurements in mice (vasculature, skeletal muscles, etc., anesthetized or fully awake). The current method we use is widely applicable for use with a multitude of available biosensors.
b. Fairfax ST, Mauban JR, Hao S, Rizzo MA, Zhang J, Wier WG. Ca2+ signaling in arterioles and small arteries of conscious, restrained, optical biosensor mice. Front Physiol. 2014 Oct 7;5:387. PMCID: PMC4188025.
Studies of hypertension have previously focused on pressure recordings, end organ damage, central and renal mechanisms, as well as structural remodeling especially in the vasculature. Vascular smooth muscle is regarded to increase its contractility in pathological hypertension and yet measurements of smooth muscle calcium in vivo remained unavailable. Using the abovementioned optical techniques we have determined that experimental hypertension in mice is in fact accompanied by detectable increases in cytosolic vascular smooth muscle calcium. The study represents the first determination of its kind in the intact living animal.
The control of vascular smooth muscle in arteries and arterioles is of paramount physiological importance. The steady state diameter of arteries in particular is important for homeostatic control of blood pressure and tissue perfusion. Myogenic tone is the innate ability of vascular smooth muscle cells to contract in response to distending pressure. I have recently published a manuscript that centrally unifies different steps in the mechanotransduction signaling cascade involved in the myogenic response of vascular smooth muscle. I put forth the novel idea that it is actually diacylglycerol that is centrally involved in the vasoconstriction of arteries in response to mechanical stretch. The new working hypothesis greatly improves our understanding of mechanotransduction, not only in smooth muscle cells, but in other cellular types as well. In addition, new avenues for investigation and development of pharmacological targets have been offered by the new results.
Vascular vasomotion is a fundamental behavior of the vasculature as can be seen in vivo and in vitro. I have determined that adrenergically-stimulated vasomotion in rat mesenteric arteries is critically dependent on interactions between smooth muscle cells and underlying endothelial cells. Specifically, vasomotion is critically dependent on synchronized calcium signals in smooth muscle cells and activation of particular potassium channels present in endothelial cells. The study resolved long standing questions regarding mechanisms for the generation of vasomotion. It also highlighted the importance of the heterocellular interactions between smooth muscle and endothelial cells.
b. Mauban J, Wier WG. Essential role of EDHF in the initiation and maintenance of vasomotion in rat mesenteric arteries. Am J Phys Heart Circ Phys 287: H608-H616 (2004). PMID: 15059779