SEMINAR: Empowering adult mesenchymal stem cells for cardiogenic regeneration

The Seminar: Mesenchymal stem cells (MSCs) are a prototypical adult stem cell with an ability to self-renew and differentiate into multiple tissue cell types. In the context of therapeutic applications, MSCs are emerging as a popular agent for tissue regeneration and repair because of their easy large-scale production and immunological privilege. During adult life, heart muscle cells or cardiomyocytes lose their ability to regenerate and are unable to repair the heart wall muscle after injury, infections or ischemia. In this study, we will present the cardiogenic regeneration ability of MSCs. Cardiomyocytes are the first cells to differentiate during development and heart is one of the first organs to function in the developing embryo. Heart development is exquisitely sensitive to precise temporal regulation of thousands of genes that govern developmental decisions during differentiation. We will give a perspective of how epigenetic regulation of multiple pathways primes and specifies MSCs into the cardiomyogenic lineage. The role of DNA cytosine methylation, histone modifications such as acetylation and methylation of histone tails, and small non-coding RNA controlled pre-and post-transcriptional regulation of cardiac specific gene expression will be discussed. WNT pathway is believed to possess a crucial role in cardiac development during embryogenesis and heart diseases in the adult through regulating diverse cellular processes. Role of epigenetic modification with reference to WNT associated regulators will be visited to give a perspective of its role during cardiac lineage commitment.

The Speaker: Dr Sudha Warrier obtained her PhD in 2002 from University of Madras, India in invertebrate reproductive biology. She underwent postdoctoral training (2002-2005) in Duke University, North Carolina, Medical College of Ohio and Anna University, India in cancer biology, hypertension proteomics and bioinformatics and stem cell biology. After postdoctoral training, she worked as a Senior Scientist in Frontier Lifeline Cardiovascular Hospital, Chennai, India (2006-2008). Areas of research were mesenchymal stem cell characterization from human bone marrow, cord blood and Wharton’s jelly and differentiation pathways into the cardiac lineages, role of HIF 1α in cardiac differentiation, identification of hypoxic specific markers in congenital heart diseases. After that, she was at Avesthagen Ltd, Bangalore as Functional Head in Cancer Stem Cell Division (2008-2009) studying a Drug Discovery Platform using in-house inhibitors against cancer stem cells from breast, prostate and head and neck cancers. Dr Sudha Warrier has been in the area of adult stem cells and cancer stem cells from 2006 onwards. Since joining MIRM from 2009 onwards, she has developed a model for enriching glioma stem cells and assaying for drug panels. In collaboration with Prof Arunasalam Dharmarajan of Curtin University, she has studied the role of Wnt antagonist, sFRP4 mediated chemosensitization of glioma stem cells to chemotherapeutics. In this project, she has also studied the downstream canonical and non-canonical Wnt pathways that regulate chemoresistance of glioma stem cells. Her other area of interest is in studying the mechanisms governing cardiomyocyte and endothelial regeneration from human mesenchymal stem cells and their epigenetic regulation and her group is actively involved in studying the epigenetic machinery of Wnt mediators in regulating cardiovascular regeneration.