Dr. Holly LaVoie, SC INBRE Program Coordinator and UofSC School of Medicine Columbia (USC SOMC) Professor of Cell Biology & Anatomy, recently received National Institutes of Health National Institute of General Medical Sciences (NIGMS) IDeA Co-Funding as one of the Institute’s “Administrative Supplements for Research on Women’s Health in the IDeA States.” The supplement was for LaVoie’s project entitled, “Cardiac extracellular matrix remodeling failure in postpartum maternal health" and was co-funded by NIGMS and the National Heart, Lung, and Blood Institute (NHLBI).
We are building off our previous SC INBRE DRP work with tissue inhibitor of metalloproteinase 4 (TIMP4) cardiac overexpression and gene deletion and the effects on the heart during pregnancy and lactation in mice. For the supplement, we propose studies with mice that overexpress MT-MMP1 also known as MMP14, a membrane inserted metalloproteinase. Metalloproteinases cleave proteins in the extracellular matrix and the TIMPs inhibit them. Normal tissue remodeling occurs through a balance of MMP activity and TIMP inhibition of their activity; when this gets out of balance fibrosis or other pathology can occur.
My lab is interested in the stress that pregnancy and lactation put on the heart, heart remodeling during pregnancy and how the heart remodels to a normal pre-pregnant state during the postpartum period. When the heart of pregnancy fails to remodel to the pre-pregnant state in humans, a condition called postpartum cardiomyopathy can occur which can lead to heart failure if not quickly treated. We are using mouse models to better understand this disease in women. My previous SC INBRE DRP mentor, Frank Spinale, MD, PhD, UofSC School of Medicine Associate Dean for Research and Graduate Education, had several mouse models, which overexpressed or have reduced MMPs and TIMPs levels and exhibit cardiac problems under stressed conditions, that he offered to share with my lab.
For this supplement study, I will be examining the effect of human MMP14 transgene overexpression on cardiac function and remodeling in mice during pregnancy and the postpartum period as a model for postpartum cardiomyopathy. We will evaluate heart function with the use of small animal cardiac ultrasound, protein and gene expression level changes in extracellular matrix proteins, and activity of other metalloproteinases in the heart.
About NIGMS IDeA Co-Funding
NIGMS provides IDeA co-funding to support research project grant applications from investigators within IDeA-eligible states whose proposals received meritorious scores through the peer review process but fall short of the Institute’s or Center’s payline. IDeA Co-funding is conducted once per year. More information: https://www.nigms.nih.gov/Research/DRCB/IDeA/Pages/IDeA-Co-funding.aspx
About SC INBRE
Funded by The National Institutes of Health, SC INBRE bringing together colleges and universities from across South Carolina advance biomedical research by addressing the need for increased understanding of, and treatment options for, many human diseases while training the next generation of biomedical scientists. SC INBRE provides opportunities for education, pipeline development, career development, research, infrastructure and financial support for faculty and students at the 14 member and 4 outreach intuitions in SC INBRE’s statewide network institutions. Additional opportunities for all statewide biomedical research are also provided. http://scinbre.org
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