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About Sickkids
About SickKids

Paul Delgado Olguín , PhD

Research Institute
Scientist
Translational Medicine

University of Toronto
Assistant Professor
Department of Molecular Genetics


Phone: 416-813-5080
Fax: 416-813-7480
Email: paul.delgadoolguin@sickkids.ca
Alternate Contact: Snow Deschamps
Alternate Phone: 416- 813-5133
Alternate Email: snow.deschamps@sickkids.ca

Brief Biography

Paul Delgado Olguín is a Scientist in the Translational Medicine program at The Hospital for Sick Children (SickKids) in Toronto. He is also an Assistant Professor in the Department of Molecular Genetics, University of Toronto.

Paul obtained his PhD from the Universidad Nacional Autónoma de México (National Autonomous University of Mexico). His PhD research focused on myogenic transcriptional regulation. As a postdoctoral fellow in the Gladstone Institute of Cardiovascular Disease at UCSF, Paul’s research focused on uncovering epigenetic mechanisms controlling cardiovascular development and maintenance.

Research Interests

• Epigenetic control of cardiovascular development and maintenance
• Mechanisms programming postnatal cardiovascular disease during embryogenesis  
• Function of chromatin modifiers in cardiovascular disease

Understanding how the cardiovascular system develops and maintains its function is critical. Cardiac disease is the leading cause of mortality in the adult population and the primary cause for morbidity. Furthermore, congenital heart disease affects one per cent of newborns. The genetic component of cardiovascular diseases has been the subject of active research. We know that gene mutations affecting the function of transcriptional regulators of cardiac morphogenesis cause congenital and adult cardiac disease. 

During the last few years, diverse epigenetic processes, like chromatin remodeling, miRNA-mediated gene silencing, histone acetylation, and more recently, histone methylation were shown to regulate key processes of cardiovascular development, maintenance and disease. Repressive histone methylation is essential for transcriptional stability, and thus for long-term function of cells, and continuous organ function, however, how histone methylation controls cardiovascular development and disease is poorly understood. Recent research in this field showed that the epigenetic repressor Ezh2, which is the histone methyltransferase of the polycomb repressor complex 2, is essential for cardiac development. Furthermore, Ezh2 prevents postnatal cardiac disease by stabilizing the gene expression program in differentiating cardiac progenitors. 

Thus, histone methylation operating very early during cardiovascular progenitor development might not only regulate aspects of cell differentiation and morphogenesis, but is also required for long-term cardiac homeostasis and response to pathologic stimuli in the postnatal life. This stresses the relevance of uncovering the functions of histone methylation and other epigenetic processes in cardiovascular development and maintenance to act effectively against congenital and postnatal disease.

Our laboratory uses in vivo and in vitro approaches to uncover the mechanism of action of several chromatin modifiers in controlling cardiovascular development and maintenance. We combine various approaches including phenotyping of mutant models, global analysis of chromatin structure in specific embryonic and adult cell types, and molecular biology techniques to uncover the cellular and molecular events controlling cardiovascular differentiation, organogenesis and maintenance.

Publications

Gomez-Velazquez M, Badia-Careaga C, Lechuga-Vieco AV, Nieto-Arellano R, Tena JJ, Rollan I, Alvarez A, Torroja C, Caceres EF, Roy AR, Galjart N, Delgado-Olguin P, Sanchez-Cabo F, Enriquez JA, Gomez-Skarmeta JL, Manzanares M. (2017). CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart. PLoS Genetics. 13(8):e1006985.

Chi L, Ahmed A, Roy AR, Vuong S, Cahill LS, Caporiccio L, Sled JG, Caniggia I, Wilson MD, Delgado-Olguin P. (2017). G9a controls placental vascular development by activating the Notch Pathway. Development. 144(11):1976-1987.

Delgado-Olguín P*, Dang LT, He D, Thomas S, Chi L, Sukonnik T, Khyzha N, Dobenecker MW, Fish JE, Bruneau BG. (2014). Ezh2-mediated repression of a transcriptional pathway upstream of Mmp9 maintains integrity of the developing vasculature. Development.141(23):4610-7. *Co-corresponding author.

Traister A, Li M, Aafaqi S, Lu M, Arab S, Radisic M, Gross G, Guido F, Sherret J, Verma S, Slorach C, Mertens L, Hui W, Roy A, Delgado-Olguín P, Hannigan G, Maynes JT, Coles JG. (2014). Integrin-linked kinase mediates force transduction in cardiomyocytes by modulating SERCA2a/PLN function. Nature Communications. 11;5:4533.

Chi L, Delgado-Olguín P. (2013). Expression of NOL1/NOP2/sun domain (Nsun) RNA methyltransferase family genes in early mouse embryogenesis. Gene Expression Patterns. 13(8):319-27.

Cheng HS, Sivachandran N, Lau A, Boudreau E, Zhao JL, Baltimore D, Delgado-Olguin P, Cybulsky MI, Fish JE. (2013). MicroRNA-146 represses endothelial activation by inhibiting pro-inflammatory pathways. EMBO Molecular Medicine. 5(7):1017-34.

Delgado-Olguín P, Huang Y, Li X, Christodolou D, Seidman CE, Seidman JG, Tarakhovsky A, Bruneau BG. (2012).  Epigenetic repression of cardiac progenitor gene expression by Ezh2 is required for postnatal cardiac homeostasis. Nature Genetics. 44:343-7.

Zhang SS, Kim K, Rosen A, Smyth JW, Sakuma R, Delgado-Olguín P, Davis M, Chi NC, Puviindran V, Gaborit N, Sukonnik T, Wylie JN, Brand-Arzamendi K, Farman G, Kim J, Rose RA, Marsden PA, Zhu Y, Zhou Y, Miquerol L, Henkelman MR, Stainier DYR, Shaw RM, Hui CC, Bruneau BG, Backx PH. (2011) Iroquois homeobox gene 3 establishes fast conduction in the cardiac His-Purkinje network. Proc Natl Acad Sci U S A. 16:13576-13581.

Delgado-Olguín P, Recillas-Targa F. Chromatin structure of pluripotent stem cells and induced pluripotent stem cells. (2011). Briefings in Functional Genomics. 10:37-39.

Wyngaarden LA, Delgado-Olguín P, Su IH, Logan MP, Tarakhovsky A, Bruneau BG, Sevan Hopyan. (2011) Epigenetic determination of proximodistal limb bud fate by Ezh2. Development. 138:3759-3767.

Delgado-Olguín P, Brand-Arzamendi K, Scott IC, Stainier DY, Recillas-Targa F, Bruneau BG. (2011) CTCF regulates myogenic development by modulating the activity of myogenic regulatory factors. Journal of Biological Chemistry. 286:12483-12494.

Takeuchi JK, Togi K, Lou X, Alexander J, Delgado-Olguín P, Holloway A, Mori A, Munson C, Wylie J, Sukonnik T, Kaynak B, Zhu Y, Yuqing Zhou, Yeh R. Henkelman M, Harvey R, Izumo S, Metzger D, Chambon C, Stainier DY, Pollard K, Scott IC, Bruneau BG. (2011) Chromatin Remodeling Complex Dosage Modulates Transcription Factor Function in Cardiogenesis and Congenital Heart Disease. Nature Communications. 2:187

Ieda M, Fu JD, Delgado-Olguín P, Vedantham V, Hayashi Y, Bruneau BG, Srivastava D. (2010) Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell. 142:375-86.

Delgado-Olguín P, Takeuchi JK, Bruneau BG. (2006). Chromatin modification and remodeling in heart development. Sci. World J. 6:1851–1861.

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