Research Directions in the Patterson Lab
Validation of the genetic underpinnings of cardiomyocyte ploidy and heart regeneration
Michaela’s postdoctoral work examined the relationship between cardiomyocyte ploidy and myocardial regeneration. Using a collection of 120 inbred mouse strains known as the Hybrid Mouse Diversity Panel, she uncovered multiple genetic loci associated with cardiomyocyte ploidy. She went on to validate the causative gene from the first locus, which proved to be Tnni3k.
The Patterson Lab has multiple projects underway (along with others still looking for a project lead) surrounding the other loci to arise from this screen. Using a variety of reverse genetic tools, including genetically engineered mice, viral induction, and more, some of the questions we commonly ask are:
Is a candidate gene in the locus responsible for cardiomyocyte ploidy phenotypes AND what role do they play post-MI?
Do the candidate genes have “functional” variants and what effect do they have on the gene’s molecular function and on ploidy?
How do multiple genes, which individually influence ploidy, act together?
Not all candidate genes function in cardiomyocytes, but instead act indirectly through another cell. What other cell types influence cardiomyocyte ploidy and MI outcomes?
Developmental progression of cardiomyocyte ploidy and its function
Outside of regeneration and post-MI outcomes, we’re very interested in how polyploidy is established in development and what physiological role it plays in the naïve heart.
Recent work from the lab uncovered that the establishment of polyploidy in postnatal mammalian development can take quite distinct paths depending on the genetic background of the individual. Further, we report the first example of ploidy reversal in cardiomyocytes. Swift et al., Development, 2023.
Unique genetic resources to identify more players in cardiomyocyte polyploidization and MI outcomes
Michaela’s postdoctoral research utilized the Hybrid Mouse Diversity Panel, a collection of inbred mouse strains designed to support genome-wide association studies. Our colleagues at the Medical College of Wisconsin have recently rederived the rat equivalent resource - the Hybrid Rat Diversity Panel. The rat panel has many benefits that make it a superior genetic resource to the mouse panel, most notably that it is four times more genetically diverse. We have multiple projects underway, many of them collaborative, to examine a multitude of phenotypes across the Rat Panel. Phenotypes range from assessment of relevant cell populations, to basal heart physiology, to MI outcomes, and more. This arm of the Patterson lab has endless possibilities for expansion.
Polyploidy in other cell types
Cardiomyocytes are not the only somatic cell in the body that displays substantial polyploidy. By examining the frequency of polyploid cells in other tissues we hope to better understand the overarching function of polyploidy in cell biology and determine if cell types utilize overlapping or distinct molecular mechanisms to drive polyploidization.