powering cures, realizing futures

Kyle MacQuarrie, MD, PhD

Kyle MacQuarrie, MD, PhD

Designated Research Grant

– Chemotherapy resistance and nuclear organization in rhabdomyosarcoma

Ann & Robert H. Lurie Children’s Hospital of Chicago Foundation

Children's Hospital of Chicago

Dr. MacQuarrie has been working in rhabdomyosarcoma biology since 2007 and has published numerous papers about research in this area.

Rhabdomyosarcoma is a pediatric tumor of skeletal muscle that sometimes possesses a ‘fusion’ between two genes that leads to poor survival. In patients with metastatic tumors that have the gene fusion, survival is <10%. Studies that focus on the biology of these gene fusions have the potential to be useful in a variety of ways in improving the survival of children with rhabdomyosarcoma. While many studies on the fusion have focused on specific things that it affects (like individual genes), there is also reason to believe the fusion affects the way the parts of the cell nucleus – the control center of the cell – are organized. Dr. MacQuarrie’s recent work suggests that parts of the nucleus that change their organization in normal skeletal muscle cells fail to make these changes in rhabdomyosarcomas, and that these organizational changes may help explain why gene fusions occur in these cells. Dr. MacQuarrie is trying to understand the differences in organization that are present between the tumor cells and normal cells, relate that organization to how the cells function, and then hopefully explain the origin of these fusions.

In addition, Dr. MacQuarrie is beginning a project to look at how organization in the cells affects resistance of the tumors to chemotherapy. Many studies of chemotherapy resistance in rhabdomyosarcoma has focused on individual factors and their impact, and Dr. MacQuarrie’s work will instead focus on the changes that occur in organization as a whole over time, not just the individual factors. He hopes understanding that organization will identify new ways to make resistant tumor cells sensitive to chemotherapy and improve our treatment of children with tumors that reoccur or are resistant to treatment when they first occur.

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