2016 SADII-SCORE Awardee, Johns Hopkins
Dr. Rosanne Rouf , Assistant Professor of Medicine, is investigating not only the reason mitral valve prolapsed, but why the disorder is so much more common in women than in men. She has developed a mouse which has a mutation in a gene associated with the development of the mitral valve. Female mice with the mutation have a much more severe type of mitral valve prolapse than males with the same mutation. Dr. Rouf’s work is an interesting illustration of how complicated it is to try to link a single gene to illness: the same gene is often expressed differently in males and females. The sex chromosomes themselves, hormones, age and environment also impact gene expression and play a role, as in this case of the uneven impact of the mutation, which by itself does not explain its different consequences in males and females. Dr. Rouf is investigating the mechanism of sex disparity in the pathogenesis of myxomatous valvular disease by using a mouse model that harbors a gene mutation that causes severe mitral valve prolapse in female mice. Male mice that harbor the same mutation have mitral valve prolapsed but to a much milder degree. To examine this difference between the sexes, Dr. Rouf and collaborators have developed high resolution imaging techniques to quantify structural and functional mitral valve disease in mice. She will employ genetic and pharmacologic strategies to identify signaling pathways which are differentially regulated between the sexes. Given the concordant association of MVP with female sex in both this murine model and in people, she expects that this research program will also serve a long-range aim of identifying novel pathways in sex-dependent mechanisms of disease.