JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE
Dr. Jennifer Mammen, Dr. Kendall Moseley, Dr. Marlene Williams, Doctor Rosanne Rouf, Dr. Kristin Voegtline.
We now have increasing evidence that hormones impact the formation of the embryonic and fetal brain; Doctor Voegtline is looking into the impact of the hormones that cross the placenta and target that brain while the baby is still in the uterus. She believes that testosterone may have a different impact on boy and girl fetuses. Dr. Kristin Voegtline, Assistant Professor of Pediatrics, is a developmental psychobiologist studying the organizational effects of the prenatal period on development after birth. Among organizing signals of the intrauterine environment, she is particularly interested in maternal sex steroids which may cross the placenta and target the fetal brain. In prior work, she has shown prenatal maternal testosterone levels are related to altered growth and neural maturation in fetuses and infants, and that effects are most pronounced for males. Dr. Voegtline will now test the hypothesis that prenatal testosterone exposure leaves an epigenetic mark via alterations to DNA methylation, a measure of gene functional capacity, and that testosterone action at the genetic level may be different for males and females.
Doctor Rosanne Rouf
Doctor 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.
Dr. Jennifer Mammen
Dr. Jennifer Mammen, Instructor in Endocrinology, is studying the ways in which gender affects autoimmune disorders, or conditions that occur when the immune system mistakenly attacks and destroys healthy body tissue. These disorders affect women more frequently than men, but the specific effects of gender are not clear. Dr. Mammen and her team focus their research on thyroid disease, which shows an overwhelming female bias. Biphasic thyroiditis, for example, frequently appears in women after pregnancy. Characterized by lymphocytic gland infiltration, this postpartum thyroid disease usually occurs in women with anti-thyroid peroxidase (anti-TPO) antibodies. Dr. Mammen’s team has found that interferon (IFNa) causes high rates of biphasic thyroiditis in women more often than men at a ratio of 8:1. This suggests the direct role of interferon in causing or spreading thyroid autoimmunity. Dr. Mammen’s team is using both in vitro and in vivo techniques to study the effects of inflammatory activation (mediated by interferons) on the autoimmune target itself. The study looks at gender-specific variability in the expression of thyroid genes such as those regulated by IFNa and/or estradiol.
Dr. Kendall Moseley
Dr. Kendall Moseley, Assistant Professor of Medicine, has set out to demystify sex-specific differences in bone quality in men and women with type 2 diabetes mellitus (T2DM). Despite high bone mineral density (BMD), persons with T2DM are at increased risk for hip fracture compared to those without diabetes. Hip geometry is one measure of bone quality that has not been evaluated in men and women with T2DM. Insufficient hip geometry, or how bones withstand outside bending and crushing forces, could cause men or women to be at higher risk for fracture. Dr. Moseley and her team suspect that with worsening glucose control, hip geometry measurements of bone quality decline despite good bone density. Moreover, they suspect there are important gender differences in the hip geometry of men and women with T2DM that could make one group at greater fracture risk as blood glucose soars out of control. Read More
Dr. Marlene Williams
Dr. Marlene Williams, Assistant Professor of Medicine, is investigating the gender differences in depression and heart disease. People with cardiovascular disease and depression are at higher risk for heart attacks and death. Since women are twice as likely to suffer from depression, the question remains whether depressed women with heart disease are also more likely than depressed men with heart disease to have more complications of heart disease. Dr. Williams thinks the answer lies with her research on the role of platelets in coronary artery disease. Depletion of a protein called brain-derived neurotrophic factor (BDNF) can lead to decreased survival of brain cells found in depression. BDNF is a member of the nerve growth factor family. It encourages neural and synaptic growth and plays a critical role in the survival, differentiation, neuronal strength, and morphology of neurons. The vast majority of blood BDNF is stored in platelets. If successful, Dr. Williams’s research could have major clinical implications. Medications that normalize BDNF levels could treat both heart disease and depression.