Genetic and Cellular Engineering
Members of our program were early adopters of gene editing technology for cardiovascular investigation in zebrafish. We continue to use this technology to engineer cells to probe mechanisms of cardiovascular development, disease and regeneration. An area of particular interest involves the manipulation of cell ploidy and the impact of this on the potential of the heart to regenerate. Other large areas of interest lie in the manipulation of cellular autophagy and the impact of epigenetic modification by histone deacetylases on vascular and myocardial pathophysiology.
Malhotra R, Mauer AC, Lino Cardenas CL, Guo X, Yao J, Zhang X, Wunderer F, Smith AV, Wong Q, Pechlivanis S, Hwang SJ, Wang J, Lu L, Nicholson CJ, Shelton G, Buswell MD, Barnes HJ, Sigurslid HH, Slocum C, Rourke CO, Rhee DK, Bagchi A, Nigwekar SU, Buys ES, Campbell CY, Harris T, Budoff M, Criqui MH, Rotter JI, Johnson AD, Song C, Franceschini N, Debette S, Hoffmann U, Kalsch H, Nothen MM, Sigurdsson S, Freedman BI, Bowden DW, Jockel KH, Moebus S, Erbel R, Feitosa MF, Gudnason V, Thanassoulis G, Zapol WM, Lindsay ME, Bloch DB, Post WS and O’Donnell CJ. HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype. Nat Genet. 2019;51:1580-1587.
Gonzalez-Rosa JM, Sharpe M, Field D, Soonpaa MH, Field LJ, Burns CE and Burns CG. Myocardial Polyploidization Creates a Barrier to Heart Regeneration in Zebrafish. Dev Cell. 2018;44:433-446 e7.
Simonson B, Subramanya V, Chan MC, Zhang A, Franchino H, Ottaviano F, Mishra MK, Knight AC, Hunt D, Ghiran I, Khurana TS, Kontaridis MI, Rosenzweig A and Das S. DDiT4L promotes autophagy and inhibits pathological cardiac hypertrophy in response to stress. Sci Signal. 2017;10.
Hwang WY, Fu Y, Reyon D, Maeder ML, Kaini P, Sander JD, Joung JK, Peterson RT and Yeh JR. Heritable and precise zebrafish genome editing using a CRISPR-Cas system. PLoS One. 2013;8:e68708.
Sander JD, Cade L, Khayter C, Reyon D, Peterson RT, Joung JK and Yeh JR. Targeted gene disruption in somatic zebrafish cells using engineered TALENs. Nat Biotechnol. 2011;29:697-8.