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Dr Branko V. Latinkic

Dr Branko V. Latinkic

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School of Biosciences

Email
latinkicb@cardiff.ac.uk
Telephone
+44 (0)29 2087 5784
Fax:
+44 (0)29 2087 4116
Campuses
Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX
Users
Available for postgraduate supervision

Overview

We study the molecular and cellular mechanisms of early heart development in vertebrates, with particular focus on cardiac specification and differentiation. Our long-standing model for these studies has been the frog (Xenopus) embryo. Recently we have complemented this in vivo model by human iPS cells, which can be readily differentiated into cardiomyocytes to provide an excellent in vitro model of cardiogenesis.

Biography

  • 1987. BSc in molecular biology, Belgrade University.
  • 1994. PhD in molecular genetics, University of Illinois at Chicago.
    Regulation of mammalian immediate-early genes, the lab of Prof. Lester Lau.
  • 1995-1998. Postdoc with Dr. Jim Smith, National Institute for Medical Research, Mill Hill. Mechanisms of mesoderm induction.
  • 1999-2003. Postdoc with Dr. Tim Mohun, National Institute for Medical Research, Mill Hill. Mechanisms of cardiac induction and gene expression.
  • 2004- Lecturer in School of Biosciences, Cardiff University.

Publications

2019

2016

2015

2014

2012

2010

2009

2008

2006

2004

2003

2002

2001

2000

In vertebrates, cardiac precursors are specified during gastrulation, almost simultaneously with major developmental decisions that will shape the embryo. Because of this, it is challenging to directly investigate cardiac specification in vivo.

Our model of choice for studying early heart development is an ex vivo assay that allows experimental manipulation and features rapid and robust cardiac differentiation. It is based on pluripotent animal pole explants derived from blastula stage Xenopus embryos. In isolation these explants normally develop into epidermis, but can be converted into cardiomyocytes by activin/Nodal signalling or by cardiogenic transcription factor GATA4, in ~ 2 days post fertilisation. In addition, the Xenopus embryo model has well-established loss- and gain-of function approaches for studying gene function.

Cardiogenesis triggered by GATA4 in pluripotent ectodermal cells recapitulates normal course of cardiomyocyte differentiation as it occurs in vivo and represents a simple tractable model which has allowed us to investigate molecular determinants of cardiogenic activity of GATA4 as well as the key targets regulated by GATA4.

We have recently established in our group a model for human cardiogenesis based on induced Pluripotent State Cells (iPSCs). iPSCs can be efficiently differentiated into cardiomyocytes (iPSC-CMs), providing an accessible model for dissecting molecular mechanisms guiding human cardiac differentiation (see Figure for an example of iPSC-CMs generated in our group) . We are currently using the iPSC-CM model to verify GATA4 targets identified in Xenopus embryos. In collaboration with consultant cardiologist Zaheer Yousef we are also using iPSC-CMs to develop ‘disease in a dish’ models of hypertrophic cardiomyopathies using genetic information and somatic cells for generation of iPSCs from patients with established family pedigrees.

Current Funding

- British Heart Foundation

Collaborators

Prof. M. Nemer - Ottawa

Prof. Nick Allen – Cardiff

Prof. Chris Denning- Nottingham

Prof. Zaheer Yousef - Cardiff

Co-workers

Pavel Kirilenko

Nicola Graham

Gabrielle Evans

Beth Burgess

External profiles

Images

Research links