CARDIOLOGY
Fish and humans have similar circulatory systems . Molecular biologist Christian Mosimann , PhD , and team can color-code them to understand how they develop .
Circulating Cast
Q : What can aquarium sealant , fish embryos and immune cells tell researchers about pediatric heart failure ?
Pediatric heart disease is rare and heterogenous , which makes it difficult to study . Across several labs at Children ’ s Hospital Colorado and the Anschutz Medical Campus , teams of researchers , many of them post-doctorate and junior faculty , are investigating the early heart from an ever-growing array of angles .
Pediatric cardiologist Stephanie Nakano , MD , is gluing a heart cell to a machine . The cell came from a tissue bank of diseased hearts taken , with consent , from nearly every patient who gets a heart transplant at Children ’ s Colorado . The glue is regular old aquarium sealant , the kind you can get at a pet store .
Dr . Nakano first isolates the individual heart muscle cells . Under a microscope , she can identify the proteins that make them contact . Then she aligns the cell with the needle tips of the machine and pilots a pair of motorized micropositioners to either end of the cell . She ’ ll need to make it happen inside of three minutes , before the glue starts to cure .
“ It ’ s a pretty delicate technique ,” she says . “ It took me a long time to learn .”
Once attached , the machine will measure the precise amount of contractile force this particular cell can generate . The technique itself has been around nearly 50 years , and it ’ s been used to generate a lot of mechanical data about adult heart cells , giving rise to treatments that have led to vastly better outcomes in many forms of adult heart failure .
But those medications don ’ t work as well in kids , even for the same conditions .
Comparing the cells of kids with dilated cardiomyopathy with the literature on their adult counterparts , Dr . Nakano , along with her mentor , pediatric cardiologist Shelly Miyamoto , MD , is making progress understanding why .
“ We found some similarities between pediatric and adult patients in the failing phenotype , but also differences ,” Dr . Nakano says . “ The amount of calcium it takes to make the cells contract is similar , but the amount of cooperativity between these filament proteins is less , meaning it ’ s more difficult for the necessary proteins to bind ( 1 ). That hints at differences at the protein level .”
Understanding those differences could eventually help researchers develop new drugs , or figure out ways to tweak existing drugs , to increase their effectiveness in kids . It ’ s just one way into the deep and complex web of problems that can affect a child ’ s heart .
“ We ’ re trying to understand these problems , but we ’ re also investing in these researchers ,” Dr . Miyamoto says . “ I was a junior researcher when we started this whole thing , and the idea is that it ’ s constant turnover and growth . Leadership evolves . Projects evolve . Different labs branch off and become independent . It ’ s complementary and collaborative .”
8 | CHILDREN ’ S HOSPITAL COLORADO