Mutafova Lab

Mission

Identifying the role of local purinergic signaling in the development of bladder disorders for patients with diabetes mellitus and metabolic syndrome.

Key areas of focus

  • Emphasis on how the purinergic signaling system regulates cellular processes that are vital for cell and tissue function and survival.
  • Studying cellular sources and mechanisms of purine release, extracellular biotransformation of purine mediators, mechanisms of transmembrane and transurothelial transport of purines, and receptor and cell targets for excitatory and inhibitory purines in the bladder wall.
  • Particular interest in understanding the purinergic regulation of bladder function and its role in the development of bladder overactivity or underactivity in systemic diseases.

Lab team

Violeta Mutafova-Yambolieva, M.D., Ph.D., vice-chair and professor of physiology and cell biology, studies novel roles of extracellular purines in regulation of lower urinary tract functions. Research in the Mutafova Lab seeks to provide in-depth mechanistic insight into the process of mechanotransduction between various cell types in the bladder wall and the role of purines in this process. Specifically, the lab studies the correlation between local purinergic signaling and the development of bladder overactivity or underactivity in patients with diabetes mellitus and metabolic syndrome.

  • Violeta Mutafova-Yambolieva, M.D., Ph.D.: Principal Investigator
  • Mahsa Borhani Peikani, Ph.D.: Laboratory Technician

Notable research findings

  • Gained extensive expertise in studying purinergic signaling in blood vessels, the peripheral and central nervous systems, the enteric nervous system and the gastrointestinal and lower urinary tracts.
  • Established nicotinamide adenine dinucleotide (NAD+), ADP ribose and uridine adenosine tetraphosphate (Up4A) as novel enteric neurotransmitters.
  • Discovered mechanosensitive release of soluble nucleotidases in the bladder mucosa with complex regulation by membrane channels, membrane receptors, neuropeptides, prostaglandins and other biologically active mediators.
  • Found tissue-specific distribution of nucleotidases in the bladder wall leading to compartmentalized purine regulation of bladder excitability.
  • Proved severe purine disbalance deep in the bladder wall as a plausible main cause of diabetic bladder dysfunctions.

Equipment, technology and techniques

  • LC1200, Agilent Technologies
  • Decentralized animal bladder model
  • Ultrasensitive methodologies for measuring purine metabolism in biological samples

Active grants and research projects

  1. Urothelial Purinergic Signaling During Bladder Filling.
    • Award: R01 DK119482
    • Funding organization: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH
  2. Novel mechanisms in enteric purinergic signaling.
    • Award: P01-DK41315
    • Funding organization: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH
  3. Neuromuscular Transmission in Arteries and Veins.
    • Award: R01 HL60031
    • Funding organization: National Heart, Lung, and Blood Institute (NHLBI), NIH