TITLE:

The Emergent Heart Function: From Genetic Mutations to Architectural Malformations

DATE:

Friday, February 3rd, 2017

TIME:

3:30 PM

LOCATION:

GMCS 314

SPEAKER:

Dr. Anna Grosberg, Cardiovascular Modeling Laboratory, UC Irvine.

ABSTRACT:

The heart’s primary function is to generate pressure to move blood throughout the body, which is normally accomplished with striking efficiency and is achieved by the myocardium developing force in a regular synchronized manner. Sadly, pathologies at a large range of length-scales, from molecular (ex. a single gene mutation) to tissue architecture changes (ex. hypertrophy), negatively impact the emergent force development and pumping function. Once a defect develops at any of these scales, the cells and tissues dynamically adapt, often exacerbating the pathology. However, any intervention is hindered by the lack of understanding of the mechanisms involved. In this talk, I will give two examples to illustrate how tissue engineering in combination with computational and modeling tools can be used to elucidate the emergent relationships spanning the multi-scale structure and function of the heart. In the first example, we explored how reduction of tissue architecture anisotropy reduces cardiac contractility. To accomplish this, novel parquet cardiac tissues were engineered to separate global and local architecture effects, and it was discovered that the reduction in developed force due purely to changes in global tissue architecture (bigger than 1mm) can be predicted by an astonishingly simple model, while local changes (less than 250 microns) trigger complex biological responses. In the second example, functional consequences of a heart diseaseassociated gene mutation were studied through tissue engineering of patient specific fibroblasts. The current results serve to partially unveil the mystery of why these inherited, nuclear lamina mutations result in patients presenting with symptoms of heart disease without other organ pathologies. Through both of these stories, we show how applying engineering strategies to the multi-scale intricacies of the myocardium can deepen our understanding of the heart as well as impact real patients in the future.

HOST:

Dr. Parag Katira

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