Saturday, August 24, 2013

Through their lens: Brian Su worked on a therapy for kidney disease

This summer we're sponsoring high school interns in stem cell labs throughout California. We asked those students to contribute to our Instagram photos and YouTube videos about life in the lab, and write about their experiences.

Brian Su did a stem cell research internship this summer in the laboratory of Thomas Weimbs at University of California, Santa Barbara.
Brian Su submitted this photo of his lab notebook to our #CIRMStemCellLab Instagram feed.
I spent my summer researching Autosomal Dominant Polycystic Kidney Disease (ADPKD), a genetically inherited disorder caused by mutations in the genes PKD-1 and PKD-2 resulting in fluid filled renal cysts that lead to renal failure in half of patients over 50. I was investigating a possible drug delivery mechanism for a treatment for ADPKD, which currently is only treatable by kidney transplant or lifelong dialysis. The drug delivery method was to use dimeric IgA to bind to polymeric immunoglobulin receptors (pIgR) on the basolateral surface of kidney epithelial cells for transcytosis to the apical surface or renal cysts.

I looked for up-regulation of dimeric IgA and pIgR in untreated cystic kidneys of mice and humans. Up-regulation of dimeric IgA and pIgR would suggest increased levels of transcytosis of IgA. My lab, the Weimbs lab at UCSB, had previously found pIgR to be up-regulated in mice. My research found IgA to be also up-regulated in mice. I confirmed this with beta-actin. I also ran western blots with ADPKD human cyst fluid. When probing for IgA, I found a band higher than dimeric IgA in mice, which was likely secretory IgA. When probing for pIgR, I saw the secretory component of pIgR from when pIgR cleaves at the apical surface. Secretory IgA is dimeric IgA with the secretory component of pIgR still bound to the J-chain. My data strongly suggests that the IgA-pIgR interaction exists in human cystic kidney epithelial cells. It also finds that IgA is up-regulated as well as pIgR in mouse cystic kidney epithelial cells.

My research furthered my lab’s goal of learning more about ADPKD in the search for a treatment or cure. It did this by showing the viability of using the IgA-pIgR interaction to distribute a cyst growth inhibiting drug throughout a renal cyst as a possible method of treatment. It also strongly suggested the existence and up-regulation of the IgA-pIgR interaction in cystic kidneys, which has been less studied than IgA-pIgR interactions in mucosal epithelial cells. While learning lab techniques and developing skills this summer, my research has taken steps to help the 12.5 million people world-wide that have the disease ADPKD.

Brian Su

No comments:

Post a Comment