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Summary

After receiving an MD degree from the Sofia Medical Academy, I practiced medicine and received specialized training in internal medicine, cardiology, and pharmacology and therapeutics. I then received a Ph.D. degree in Pharmacology and Physiology from the Sofia Medical Academy and studied mechanisms of adrenergic and purinergic cotransmission in the peripheral nervous system.

In 1993 I was awarded a Fellowship from the Fogarty International Center of the National Institutes of Health (NIH) U S A to continue my studies on mechanisms of plurichemical neurotransmission in the Department of Pharmacology at the University of ÁùºÏ±¦µä School of Medicine (UNSOM) in Reno. This was followed by a postdoctoral fellowship in microelectrode methodologies in vascular research in the Department of Physiology and Cell Biology at UNSOM. I was then recruited to a faculty position in the same department and am now a Professor of Physiology and Cell Biology at UNSOM, Reno. My research is focused on neuroeffector mechanisms in the peripheral and central nervous systems with emphasis on purinergic neurotransmission and cotransmission, and has been continuously funded by the National Institutes of Health and the American Heart Association. I teach medical students in cardiovascular physiology and graduate students in neuroscience.

Education

• Ph.D., Pharmacology and Physiology, Sofia Medical Academy, 1987
• M.D., Sofia Medical Academy, 1979

Research interests

My laboratory is interested in understanding how the peripheral nervous system regulates the functions of visceral smooth muscles and blood vessels. We investigate prejunctional and post-junctional aspects of neurotransmission, including mechanisms of neurotransmitter release and neuromodulation, intercellular communications at neuroeffector junctions, and signal transduction pathways underlying neurotransmitter action. Our long-term goal is to develop methods for the prevention and treatment of conditions associated with dysfunction of the peripheral nervous system such as hypertension, abnormal vasospasm, cardiogenic shock, congestive heart failure, neurogenic bladder, and gastro-intestinal motility disorders.

Recently, my laboratory demonstrated that beta-nicotinamide adenine dinucleotide (NAD) is released along with norepinephrine and adenosine 5'-triphosphate (ATP) during nerve stimulation in blood vessels and visceral smooth muscles from a large variety of species as well as in brain neurons. NAD, not previously considered a player at the neuroeffector junction, meets key requirements defining a neurotransmitter and a neuromodulator. In some systems, NAD mimics the endogenous purine neurotransmitter better than ATP, thus adding novel aspects to the concept of plurichemical neurotransmission. Our research also suggests that multiple purine nucleotides, including "primary" purines such as NAD and ATP, as well as their immediate or distant metabolites such as ADP ribose and ADP, could also be involved in neurotransmission. Most recently, we demonstrated that uridine adenosine tetraphosphate (Up4A), a unique molecule containing both adenine and uridine moieties, is a novel neurogenic regulator of the gastrointestinal system.  The next logical step is to determine the functional correlates of these phenomena using models corresponding to physiological and pathological conditions in humans. We use neurochemistry, protein biochemistry, immunohistochemistry, functional and molecular biology techniques to study mechanisms of neurotransmission from mice with specific gene deletions, to genetically hypertensive animals, to human and non-human primates. This work has occasioned stimulating collaborations with other investigators in the department, the school and other places in the USA.

Courses taught

• PCB 711 Systems Physiology (Cardiovascular System)
• MED 632 Cardiovascular, Respiratory and Renal Systems
• CMPP 740 Neuroeffector Mechanisms: Selected Topics in Cell Signaling
• PCB 611M Systems Physiology (Cardiovascular System)

Selected publications

• Durnin L, Hwang SJ, Kurahashi M, Ward SM, Sasse KC, Sanders KM, V Mutafova-Yambolieva. Uridine adenosine tetraphosphate (Up4A) is a novel neurogenic P2Y1 receptor activator in the gut.  Proceedings National Academy of Sciences U S A  111(44):15821-6, 2014.
• Mutafova-Yambolieva VN and L Durnin. The purinergic neurotransmitter revisited: a single substance or multiple players?  Pharmacology & Therapeutics , 144(2):162-191, 2014.
• Kurahashi M, Mutafova-Yambolieva V, Koh S D and K M Sanders. Platelet-derived growth factor receptor a-positive cells and not smooth muscle cells mediate purinergic hyperpolarization in murine colonic muscles.  American Journal of Physiology Cell Physiology, 307(6):C561-70, 2014.
• Peri LE, Sanders KM, and V Mutafova-Yambolieva. Differential expression of genes related to purinergic signaling in smooth muscle cells, PDGFRA-positive cells, and interstitial cells of Cajal in the murine colon.  Neurogastroenterology & Motility, 25(9):e609-20, 2013.
• Durnin L, Sanders KM and V Mutafova-Yambolieva. Differential release of b-NAD+ and ATP upon activation of enteric motor neurons in primate and murine colons. Neurogastroenterology & Motility; 25(3):e194-204, 2013.
          - Highlighted in: Neurogastroenterology: Colonic motor neurotransmission-is b-NAD+ in control? Smith K,  Nat Rev Gastroenterol Hepatol; 10(2):64, 2013.
• Mutafova-Yambolieva VN. Neuronal and extraneuronal release of ATP and NAD+ in smooth muscle. IUBMB Life; 64(10):817-824, 2012
• Hwang SJ, Blair PJ, Durnin L, Mutafova-Yambolieva V, Sanders KM and SM Ward - P2Y1 purinoreceptors are fundamental to inhibitory motor control of murine colonic excitability and transit.  Journal of Physiology; 590(Pt 8):1957-72, 2012.
         - Comment in: Resolution and concordance in dissecting the compound inhibitory junction potential. King BF,  Journal of Physiology; 590(Pt8): 1777-8, 2012.
• Durnin L, Hwang SJ, Ward SM, Sanders KM, and VN Mutafova-Yambolieva. Adenosine 5'-diphosphate-ribose (ADPR) is a neural regulator in primate and murine large intestine along with β-NAD+.  Journal of Physiology; 590(Pt 8):1921-41,2012.
• Durnin L, Dai YP, Aiba I, CW Shuttleworth, Yamboliev IA, VN Mutafova-Yambolieva - Release, neuronal effects and removal of extracellular β-nicotinamide adenine dinucleotide (β-NAD+) in the rat brain.  European Journal of Neuroscience; 35(3):423-35, 2012.
• Hwang SJ, Durnin L, Dwyer L, Rhee PL, Ward SM, Koh SD, Sanders KM, and VN Mutafova-Yambolieva - β-nicotinamide adenine dinucleotide is an enteric inhibitory neurotransmitter in human and nonhuman primate colons.  Gastroenterology, 140: 608-617.e6, 2011.
    - Comment in: A new player in neuromuscular transmission in the gastrointestinal tract. Rodriguez-Tapia E, Galligan JJ.  Gastroenterology. 140(2):397-400, 2011.
• Durnin L, VN Mutafova-Yambolieva - Cyclic ADP-ribose (cADPR) requires CD38 to regulate the release of adenosine 5'-triphosphate (ATP) in visceral smooth muscle,  FEBS Journal; 271:3095-3108, 2011.
• Yamboliev IA, Smyth LM, Durnin L, Dai Y-P, VN Mutafova-Yambolieva - Storage and secretion of β-NAD, ATP and dopamine in NGF-differentiated rat pheochromocytoma PC12 cells.  European Journal of Neuroscience; 30:756-768, 2009.
• Smyth LM, Yamboliev IA, VN Mutafova-Yambolieva - N-type and P/Q-type calcium channels regulate differentially the release of noradrenaline, ATP and β-NAD in blood vessels.  Neuropharmacology; 56(2):368-378, 2009.
• Mutafova-Yambolieva VN, Hwang SJ, Hap X, Chen H, Zhu MX, Wood JD, Ward SM, Sanders KM - β-nicotinamide adenine dinucleotide is a new inhibitory neurotransmitter in visceral smooth muscle.  Proceedings National Academy of Sciences USA; 104(41):16359-64, 2007.
• Bobalova J, VN Mutafova-Yambolieva - Activation of the adenylyl cyclase-protein kinase A pathway facilitates neural release of β-nicotinamide adenine dinucleotide (β-NAD) in canine mesenteric artery.  European Journal of Pharmacology; 536, 128-132, 2006.
• Smyth LM, Breen LT, Yamboliev IA, VN Mutafova-Yambolieva - Novel localization of CD38 in perivascular sympathetic nerve terminals.  Neuroscience; 139 (4): 1467-1477, 2006.
• Smyth LM, Breen LT, VN Mutafova-Yambolieva - Nicotinamide adenine dinucleotide (NAD) is released from sympathetic nerve terminals via a botulinum neurotoxin A mediated mechanism in canine mesenteric artery.  Am J Physiol Heart and Circ Physiol. 290(5), H1818-H1825, 2006.
• Dai Y-P, Bongalon S, Tian H, Mutafova-Yambolieva V, IA Yamboliev - Upregulation of profilin, cofilin-2 and LIMK2 in cultured pulmonary artery smooth muscle cells and in pulmonary arteries of monocrotaline-treated rats.  Vascular Pharmacology; 44(5), 275-282, 2006.
• Breen LT, Smyth LM, Yamboliev IA, VN Mutafova-Yambolieva - β-NAD is a novel nucleotide released upon stimulation of nerve terminals in human urinary bladder detrusor muscle.  Am J Physiol Renal Physiology; 290(2), F486-F495, 2006.
• Yamboliev IA, VN Mutafova-Yambolieva - PI3K and PKC contribute to membrane depolarization mediated by alpha2-adrenoceptors in the canine isolated mesenteric vein.  BMC Physiol. 15, 5:9, 2005.
• Smyth LM, Bobalova J, Mendoza MG, Lew C, and VN Mutafova-Yambolieva - Release of β-nicotinamide adenine dinucleotide upon stimulation of postganglionic nerve terminals in blood vessels and urinary bladder.  J Biol Chem. 279(47), 48893-48903, 2004.