Violeta Mutafova-Yambolieva M.D., Ph.D.: Biography/Education

Professor

Cellular and Molecular Pharmacology & Physiology | Department of Physiology and Cell Biology

Curriculum vitae

Education

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

Biography

After receiving an M.D. 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) USA to continue my studies on mechanisms of plurichemical neurotransmission in the Department of Pharmacology at the University of Nevada, Reno School of Medicine. This was followed by a postdoctoral fellowship in microelectrode methodologies in vascular research in the Department of Physiology and Cell Biology at the University of Nevada, Reno School of Medicine. I was then recruited to a faculty position in the same department and am now a Professor of Physiology and Cell Biology at the School of Medicine. 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.

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)

Research

My laboratory is interested in understanding how the peripheral nervous system regulates the functions of visceral smooth muscles and blood vessels. We investigate pre-junctional 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, overactive or underactive 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. We also 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.

Most recently, my laboratory has also become interested in studying novel aspects of extracellular purine signaling in the lower urinary tract. We investigate mechanosensitive release and transport of purines in the urothelium during bladder filling and strive to understand how urothelium-derived purines regulate functions of multiple cell types in the bladder wall, including detrusor smooth muscle cells, submucosal interstitial cells and cells in the bladder mucosa. Of particular importance to this research is the use of a new model of decentralized mammalian bladder lacking the detrusor muscle along with integrated experimental approaches in transgenic mice and in primate bladders.

We use neurochemistry, protein biochemistry, immunohistochemistry, functional, molecular biology and imaging techniques to study mechanisms of neurotransmission and purine signaling from mice with specific gene deletions, to mice expressing green fluorescent proteins or optogenetic Ca2+ sensors in specific cells types, 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.


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