Cheryl Maslen, PhD

Rare disorders studied

Biographical information

Cheryl Maslen received her doctorate from OHSU’s Department of Medical Genetics in 1987.  She did her postdoctoral training in molecular genetics and biochemistry at Shriners Hospital for Children. Dr. Maslen joined the faculty at OHSU in 1991, and was awarded the Richard T. Jones, MD, PhD, Distinguished Alumni Scientist Award in 2007.  Dr. Maslen is currently a professor of Cardiovascular Medicine, and Molecular & Medical Genetics in the OHSU School of Medicine, and is Associate Director of the OHSU Heart Research Center.  She is also a principal investigator for The National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Related Conditions (GenTAC) and directs the project’s Northwest Center, one of five regional clinical centers.

Research interests

The major research focus of the Maslen laboratory is on the determining the molecular genetic basis of congenital heart defects. Since the majority of congenital heart defects occur sporadically, it is clear that they are complex traits with oligogenic inheritance.  This indicates that multiple genes acting as risk factors or susceptibility traits will collectively be the causative factors for most heart malformations.  In a major advance in this field we identified a new cell adhesion protein, CRELD1, and demonstrated that mutations in the CRELD1 gene act as genetic risk factors for atrioventricular septal defects, a common heart malformation.  This is the first identified susceptibility gene for a sporadically occurring cardiac septal defect, and as such expands our understanding of congenital heart defects as genetically complex traits.  We have created and are characterizing a mouse model, and have identified mutations in CRELD2 as an additional risk factor.  More recently we have determined that CRELD1 mutations contribute to the occurrence of heart defects in Down syndrome.  This led to the development of a national level program, The National Down Syndrome Heart Project, with investigators at Johns Hopkins and Emory Universities.  This project is based on the concept that children with Down syndrome are at a 2000-fold increased risk for having a heart defect. This provides an opportunity for identifying genetic risk factors in this highly sensitized population through patient-oriented research coordinated with basic investigations using mouse models.

Another area of interest is in the genetic basis of conditions that predispose to thoracic aortic aneurysms.  As a principal investigator for GenTAC I am participating in developing the national registry for thoracic aortic aneurysm/dissection (TAAD), and the research projects that are fundamental to this study. We will be doing analyses of genetic risk factors that are associated with TAAD. This study involves several rare disorders including Marfan syndrome, Turner syndrome, familial TAAD, Loeys-Dietz syndrome, vascular Ehler-Danlos syndrome (EDS IV), bicuspid aortic valve disease, and congenital heart disease with aortic enlargement.  The goal of of this study is to identify the genetic and environmental risk factors underlying genetically triggered thoracic aortic aneurysms.


Rare disorders activities

Co-investigator, CTSA supplement award for “Virtual Biobanks for Multicenter Research on Pediatric Rare Diseases”

Online reviews and articles of interest

Frederic M, Monino C, Marschall C, et al.  The FBN2 gene: new mutations, locus-specific database (UMD-FBN2) and genotype-phenotype correlations.  Hum Mutat. 2008 Sep 2. [Epub ahead of print]

Maslen CL. The molecular genetics of atrioventricular septal defects.  Current Opinion in Cardiology 2004; 19(3): 205-210.

Maslen CL, Babcock D, Redig JK, et al. CRELD2: Gene mapping, alternate splicing, and comparative genomic identification of the promoter region.  Gene 2006; 382: 111-20.

Maslen CL, Babcock D, Robinson SW, et al. CRELD1 mutations contribute to the occurrence of cardiac atrioventricular septal defects in Down syndrome.  Am J Med Genet ; 140(22): 2501-5.

Pearson GD, Devereux R, Loeys B, et al.  Report of the National Heart, Lung and Blood Institute and National Marfan Foundation Working Group on research in Marfan syndrome and related disorders.  Circulation 2008;118(7):785-91.

Robinson SW, Morris CD, Goldmuntz E, et al. Missense mutations in CRELD1 are associated with cardiac atrioventricular septal defects.  Am J Hum Genet 2003; 72: 1047-1052. 

Rupp PA, Fouad GT, Egelston CA, et al. Identification, genomic organization and mRNA expression of CRELD1, the founding member of a unique family of matricellular proteins. Gene 2002; 293: 47-57. 

Tomita-Mitchell A, Maslen CL, Morris CD, et al.  GATA4 mutations in patients with congenital heart disease.  J Med Genet 2007; 44:779-783.