91大香蕉

My main areas of research focus are blood coagulation and pregnancy complications. Blood clots are necessary to protect us from excessive bleeding when we get injured. Blood clots can also cause conditions such as stroke and heart attack. While I enjoy studying all aspects of blood clotting, my focus is on thrombophilia, a condition that leads to pathological blood clot formation. I am most passionate about understanding the mechanisms by which thrombophilia adversely affects placental function and maternal-fetal health.

Abnormalities in placental function causes complications such as abruption, fetal growth restriction, stillbirth, preterm birth, and preeclampsia, which collectively impact more than 15% of human pregnancies. These complications carry a heavy burden of immediate adverse outcomes for mothers and babies, and a life-long impact on the cardiovascular, neurological, and metabolic health. Thrombophilia has long been suspected to be associated with pregnancy complications. My laboratory has developed and utilized murine models of fetal and maternal thrombophilia to investigate this epidemiological association and have contributed to the field by establishing causation. We have shown that fetal thrombophilia impairs placental function due to reduced or absent anticoagulant gene expression on extraembryonic cells that reside in the placenta and invade the mother’s uterus. The impairment of placental function in turn causes intrauterine growth restriction, fetal demise, and poor neonatal survival. Blood clots in venous return channels of the placenta are one potential cause of poor placental function due to fetal thrombophilia. Importantly, our studies show that fetal/neonatal demise due to fetal thrombophilia is caused by suboptimal placental function and there are potential approaches to treat this condition and prevent an adverse outcome. In contrast to fetal thrombophilia, we found that maternal thrombophilia results in blood clots in the decidua, the innermost lining of the uterus to which the placenta is attached. Pregnant mice with thrombophilia exhibit midterm uterine bleeding and fetal growth restriction, both hallmarks of placental abruption. Our studies further indicate that maternal platelets and thrombin receptor Par4 play key roles in placental dysfunction due to maternal or fetal thrombophilia. Through these studies, we have demonstrated that endogenous anticoagulants play a critical role in maintaining uterine and placental health. While thrombotic events such as strokes, heart attacks, and pulmonary embolism are a leading cause of adult morbidity and mortality, thrombotic events in the placenta could be equally devastating for the unborn fetus.

I highlight here two research projects being currently pursued in my laboratory. One NIH funded project is focused on studying the role of coagulation components, immune cells and inflammatory mediators in the onset and progression of placental abruption. A second research project is funded through the Clinical and Translational Research Institute and is focused on identifying biomarkers that can be used to predict preterm birth and time-to-delivery.

In addition to research, I enjoy teaching in MCW’s graduate and medical school programs and mentoring students and junior faculty at all stages of career and from diverse backgrounds. My laboratory supports summer training of high school and undergraduate interns selected through the internship programs on our campus. All members of my laboratory including two postdoctoral fellows, two graduate students, and a laboratory technician participate in mentoring others at stages of career earlier than their own. Together, we strive to address outstanding problems in maternal-fetal health and help build the next generation of scientists.

Basil O鈥� Connor Starter Scholar Award, March of Dimes Foundation
Scientist Development Grant, American Heart Association
Fellow of the American Heart Association
R01HL112873 鈥淩ole of maternal platelets in placental and pregnancy complications鈥�, National Institutes of Health
Research Award 鈥淚mmune crosstalk in preterm birth鈥�, Advancing a Healthier Wisconsin Endowment
R01HL163623 鈥淐oagulation-inflammation crosstalk in placental abruption鈥�, National Institutes of Health

• Blood coagulation
• Uterine and placental hemostasis
• Thrombophilia and pregnancy complications
• Placental abruption
• Birth timing and biomarkers of preterm birth
• Coagulation-inflammation crosstalk
• Extraembryonic tissue development
• Maternal-placental-fetal health