Featured Grad Paper: Sumeeta Warraich

The Role of Equilibrative Nucleoside Transporter 1 (ENT1) in the Progressive Development of Ectopic Mineralization in Spinal Tissues Resembling Diffuse Idiopathic Skeletal Hyperostosis (DISH) in Humans

 

Warraich S, Bone DB, Quinonez D, Ii H, Choi DS, Holdsworth DW, Drangova M, Dixon SJ, Séguin CA, Hammond JR.
J Bone Miner Res. 2012 Nov 26. doi: 10.1002/jbmr.1826. [Epub ahead of print]

 

Sumeeta WarraichSummary of paper:

According to The Arthritis Society, the second most common form of arthritis after osteoarthritis is diffuse idiopathic skeletal hyperostosis, abbreviated as DISH.  It affects between 6 and 12 percent of North Americans, usually people older than 50. DISH is classified as a form of degenerative arthritis and is characterized by the formation of excessive mineral deposits along the sides of the vertebrae of the spine. Symptoms of DISH include spine pain and stiffness and, in advanced cases, difficulty swallowing and damage to spinal nerves. The cause of DISH is unknown and there are no specific treatments. 

Equilibrative Nucleoside Transporter 1 (ENT1) is a membrane protein involved in the bi-directional transfer of hydrophilic nucleosides, such as adenosine. In mice lacking ENT1, development of calcified lesions resembling DISH was observed. By 12 months of age, ENT1-/- mice exhibited signs of spine stiffness, hind limb dysfunction, and paralysis. Micro-CT scans revealed ectopic mineralization of paraspinal tissues which started at the base of the neck, and extended down the vertebral column with advancing age. There was no evidence of mineralization in appendicular joints or blood vessels, indicating specificity for the axial skeleton. Microanalysis of lesions revealed a high content of calcium and phosphorus with a ratio similar to that of cortical bone.  Gene expression analysis revealed significant changes in genes involved in the regulation of mineralization between ENT1-/- and wild-type controls.  This is the first report of a role for ENT1 in regulating the calcification of soft tissues. Moreover, the ENT1-/- mice may be a useful model for investigating pathogenesis and evaluating therapeutics for the prevention of mineralization in DISH and related disorders.

 

Sumeeta's Bio:

Sumeeta Warraich is a graduate student in the second year of her Masters in Physiology. She is co-supervised by Dr. James Hammond and Dr. Cheryle Séguin, where she works on a project that links two vastly different areas of research – one of purine metabolism, and the other of spinal and mineralization research. Sumeeta completed an Honours Bachelor of Science in an Integrative Biology Specialist program at the University of Toronto. Sumeeta is an advocate for mental health and was the program coordinator for the Mental Wellness Peer Education program through the campus’ Health and Wellness Centre at the University of Toronto. She played a fundamental role in educating and promoting social, emotional and psychological well-being amongst the student body. Sumeeta has been extensively involved in the community by volunteering at Holland Bloorview Kids Rehabilitation Hospital, where she assisted students that had complex medical, physical, cognitive and communication needs. She is an outreach volunteer for Let’s Talk Science at the University of Western Ontario, which aims to stimulate an interest in science for students in elementary and high schools. Sumeeta has an appreciation for clinical research and hopes to have a career in the healthcare field. Sumeeta will be defending in April 2013. 

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