Marcos specialises in direct cell reprogramming for cardiovascular diseases.

Cardiovascular diseases are the leading cause of deaths worldwide and, despite major clinical improvements, some patients undergo medical operations that improve life quality and extend their lifespan but do not improve cardiac tissue function. Approaches based on restoring the number of functional cells have been recently developed. In this field, scientists have reprogrammed cardiac fibroblasts into cardiomyocytes-like cells by delivering a defined set of transcriptional factors. Although the resulting phenotype resembles to cardiomyocytes, these cells are immature and show limited functionality. Additionally, safety concerns of current delivery vehicles must be overcome before clinical translation. My project aims to achieve targeted, efficient reprogramming of resident cardiac fibroblasts into functional cardiomyocytes in vitro and in vivo within a mouse acute myocardial infarct model. A targeted delivery system has been optimised to carry these same plasmids and is currently being assessed in terms of its ability to effect delivery of the reprogramming factors and upregulation of cardiomyocyte genes in these cells. In vitro optimisation of the ratios of this panel of factors for enhanced direct reprogramming outcomes will be achieved using a microbioreactor array that permits screening of many factorial concentrations of the factors. Optimal factors from the in vitro assay will then be utilised within our transgenic mouse and an established AMI model and reprogramming assessed by measuring the conversion of green fibroblasts to red cardiomyocytes using the transgenic mouse reporters. The converted cells will be isolated using either single cell laser dissection or FACS and thereafter phenotyped and functionally assessed using available assays.

Marcos graduated in Biochemistry from the Universidad Austral de Chile in 2012. During his undergrad he studied polymer-small molecule interactions in aqueous solution in the Polymers laboratory from Dr. Ignacio Moreno-Villoslada. He did his honours in the Centro de Estudios Cientificos (CECs-Valdivia) generating a mouse model for genetic cardiac diseases. In parallel with his studies, he worked as a research assistant in the Metabolism and Biotechnology laboratory of Prof. Alejandro Yanez at Universidad Austral de Chile using small animal models for metabolic diseases and their treatments. In 2014 Mr. Soto joined the Cooper-White laboratory to do his PhD after being granted a Becas Chile scholarship, sponsored by the Chilean Government. 

Key Publications

Stacking of 2,3,5-triphenyl-2H-tetrazolium chloride onto polyelectrolytes containing 4-styrenesulfonate groups.
Moreno-Villoslada I, Torres C, González F, Soto M, Nishide H.
J Phys Chem B. 2008 Sep 11;112(36):11244-9. doi: 10.1021/jp802668q. Epub 2008 Aug 15.

Reduction of 2,3,5-triphenyl-2H-tetrazolium chloride in the presence of polyelectrolytes containing 4-styrenesulfonate moieties.
Moreno-Villoslada I, Soto M, Gonzalez F, Montero-Silva F, Hess S, Takemura I, Oyaizu K, Nishide H.
J Phys Chem B. 2008 May 1;112(17):5350-4. doi: 10.1021/jp712093v. Epub 2008 Apr 5.