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Gabriel Baccam

Mentor: Chou-Long Huang, M.D./Ph.D.
Lab Room: 3270 CBRB
Lab Phone: 319-335-2525

Cardiac Protection by Klotho through lipid raft mediated TRPC6

Chronic kidney disease (CKD) affects approximately 30 million adults. Two thirds of CKD cases are caused by diabetes and hypertension. 95% of patients with CKD have cardiac hypertrophy, but the mechanism of cardiac hypertrophy in patients with CKD is not well understood. Our lab has shown that reduction of klotho in CKD kidneys leads to the development of cardiac hypertrophy.

We have previously shown that soluble klotho (sKL) is cardioprotective and sKL deficiency leads to an increase risk of heart failure. A reduction in serum sKL levels in CKD patients and mice have been shown to lead to aggravated cardiac pathology and the development of uremic cardiomyopathy. Overexpression of klotho protects the heart from cardiomyopathy by downregulating PI3K-dependent exocytosis of TRPC6, a Ca2+ permeable channel in the heart. We have recently identified membrane lipid rafts as receptors for sKL that mediate downregulation of PI3K and TRPC6 function in the heart. However, its mechanism of action and the pleiotropic actions of sKL have yet to be elucidated.

Our overarching hypothesis is that sKL binds to lipid rafts to exert cardiac protection and its reduction leads to the development of cardiac hypertrophy in CKD patients. The focus of my research will be to understand the mechanisms by which abnormal Ca2+ signaling mediated by TRPC6 leads to the pathogenesis of cardiac hypertrophy. Elucidating this mechanism is essential to our overall goal to understand how sKL protects the heart.

Bohnekamp J, Cryderman DE, Paululat A, Baccam GC, Wallrath LL, Magin TM . A Drosophila Model of Epidermolysis Bullosa Simplex. J Invest Dermatol. 2015 ; 135(8):2031-2039. PMID: 25830653

Baccam, G.C., Xie, J., Jin, X. et al. Glucosylceramide synthase inhibition protects against cardiac hypertrophy in chronic kidney disease. Sci Rep 12, 9340 (2022). PMID: 35660779

Honors and Awards

  • Commended Poster Award (2014): “Modeling Skin Blistering in Drosophila”
  • Graduate College Post-Comprehensive Research Fellowship - Spring 2020
  • AAAS/ Science Program for Excellence in Science- 2021