Genetics has fascinated Cheryl Maslen, PhD, since the very earliest stages of her academic career. Lately, her focus has been on the Down syndrome (DS) population as a potential avenue to uncovering genetic factors causing heart defects in the general population.

Dr. Maslen is a professor of Medicine and Molecular Genetics in the School of Medicine. She is also associate director of the OHSU Heart Research Center.

One in every 100 children is born with a heart defect. In the past, there were few options for these children. Now, the dramatic success of surgical interventions has resulted in an emerging adult population living with heart defects.

"While the hole may be surgically repaired in the infant, the underlying genetic defect remains," said Dr. Maslen. "As this new adult population increases, we need to better understand the genetic basis of the disease to be able to help these families."

Down syndrome individuals – whose condition is the result of being born with three copies of chromosome 21 instead of the normal pair – are 2,000 times more likely than the general population to develop an atrioventricular septal defect (AVSD). Dr. Maslen's research showed that mutations of the CRELD1 gene occur in about five percent of DS individuals with a complete AVSD, and appear to play a role in development of AVSD in the general population.

CRELD1 – on chromosome 3 – encodes a cell surface protein that may function as a cell adhesion molecule that is, in turn, key in embryonic development. Previous studies in the Maslen lab showed that CRELD1 mutations are a likely genetic risk factor for defects in the walls separating the heart's chambers.

Dr. Maslen has recently branched off in a novel direction, building on the infrastructure and patient recruitment of DS individuals for the heart research. Funded in part by a grant from the Oregon Clinical & Translational Research Institute, better known by it acronym, OCTRI, the new research focuses on cognitive issues.

"These kids have a broad range of mental ability – some can hold jobs and even advance through high school," said Dr. Maslen. "We want to understand why that is from a genetic perspective."

The pilot study will clinically classify the DS population based on cognitive ability and then perform a genetic analysis to characterize this variability.

"Once identified, these genetic sources of variability may become therapeutic targets for improving the lives of these individuals, and perhaps for people with other conditions that manifest cognitively," said Dr. Maslen.

Dr. Maslen is also a principal investigator in a NIH-sponsored initiative to build a national program dedicated to the study of thoracic aortic aneurysm, a commonly occurring and often deadly cardiovascular condition. The National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Related Conditions (GenTAC) consist of five regional clinical centers. Dr. Maslen directs the Northwest Center, the only in the western U.S.

In recognition of her distinguished work, Dr. Maslen received the Richard T. Jones, MD, PhD, Distinguished Alumni Scientist Award in 2007. The award honors a graduate from the OHSU School of Medicine's Masters or PhD programs. Dr. Maslen received her doctorate in 1987 from what was then the Department of Medical Genetics.