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Stokes Lab

Stokes Lab


Researchers in the Stokes Lab are focused on exploring regulatory protein mechanisms in the stressed and failing heart, specifically, ion channels and complex trans-membrane proteins.  


Members


Alexander Stokes, Ph.D. (Assistant Professor)
Cadie Buckley, B.S. (Graduate Student)
Mark Khemmani, B.S.  (Graduate Student)
Nathan Itoga, B.S. (Medical Student)
Ben Rosa (Pre-Medical Student)
Larry Renas (Research Technician)

 
Current Research


1. The Ion Channel TRPV1 

TRPV1 (transient receptor potential cation channel, subfamily V, member 1)   is a nonselective cation channel that may be activated by a wide variety of exogenous and endogenous physical and chemical stimuli. The best-known activators of TRPV1 are capsaicin, the hot component in chili peppers, and high heat great than 43˚C. The activation of TRPV1 leads to painful, burning sensation. Its endogenous activators include: low pH (acidic conditions), the endocannabinoid anandamide, N-arachidonoyl-dopamine. TRPV1 receptors are found mainly in the nociceptive neurons of the peripheral nervous system, but they have also been described in many other tissues, including the central nervous system, and tissues of the heart, circulatory systems and immune system. Among them, cardiomyocytes, cardiac blood vessels, perivascular nerves, pulmonary artery smooth muscle cells, coronary endothelial cells, skeletal muscle, mast cells, and dendritic cells. TRPV1 it is well positioned to receive multiple stimulatory signals.


    
(click on image to enlarge)                             (click on image to enlarge)


Using mice which lack functional TRPV1, we are investigating the role TRPV1 plays in the progression of cardiac hypertrophy and heart failure. We are also analyzing how TRPV1 is regulated at the molecular level using biochemistry and molecular biological tools.

(click on image to enlarge)

Reference: Created using PyMol and a homology model of the TRPV1 ion channel based on a homology model published in Brauchi S, Orta G, Mascayano C, Salazar M, Raddatz N, Urbina H, Rosenmann E, Gonzalez-Nilo F, Latorre R (June 2007). "Dissection of the components for PIP2 activation and thermosensation in TRP channels". Proceedings of the National Academy of Sciences of the United States of America 104 (24): 10246–51. DOI:10.1073/pnas.0703420104. PMID 17548815.



Normal mouse heart (left)
Hypertrophic mouse heart (right)

(click on image to enlarge)






2. TMC Family of Proteins

We also study the TMC family of proteins. Using in vivo and in vitro techniques we aim to elucidate the function and role of the TMC family of proteins in intracellular stress responses and heart stress.




  Contact Information


  

  Dr. Alexander Stokes
  Assistant Researcher
  
  
  Phone: 808-692-1633
  Fax: 808-692-1973



  
  



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