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Emily Nguyen

Mentor: Isabella Grumbach, M.D./Ph.D.
Lab Room: 4336 PBDB
Lab Phone: 319-384-4689

Mitochondrial CaMKII in Vascular Smooth Muscle Cells

Diabetic patients are at increased risk of morbidity and mortality from coronary artery disease (CAD). Diabetics experience higher rates of adverse outcomes after percutaneous balloon angioplasty (PCI), driven by stent restenosis through neointimal formation. Previous studies have postulated mitochondrial overproduction of reactive oxygen species (mitoROS) as the initiator of pathways invoked in diabetic vascular complications. However, whether inhibiting mitoROS production prevents neointima formation in diabetes remains unknown.

CaMKII is a multi-subunit kinase that can be activated by autophosphorylation or oxidation after associating with Ca2+-bound calmodulin. Recently, CaMKII was detected in mitochondria (mitoCaMKII) where it increases mitochondrial Ca2+ influx through the mitochondrial Ca2+ uniporter, which stimulates mitochondrial ROS generation.

We will examine whether mitoCaMKII regulates mitochondrial ROS and dynamics, and affects VSMC proliferation, migration, and apoptosis. Understanding the role of mitoCaMKII in neointimal hyperplasia may be a critical step towards designing a CaMKII inhibitor with the potential to prevent restenosis with particular benefit in diabetics.

Nguyen EK, Koval OM, Noble P, Broadhurst K, Allamargot C, Wu M, Strack S, Thiel WH, Grumbach IM. CaMKII (Ca(2+)/Calmodulin-Dependent Kinase II) in Mitochondria of Smooth Muscle Cells Controls Mitochondrial Mobility, Migration, and Neointima Formation. Arterioscler Thromb Vasc Biol. 2018 Mar 29. pii:ATVBAHA.118.310951. doi: 10.1161/ATVBAHA.118.310951. [Epub ahead of print] PubMed PMID: 29599132.

Zhu LJ, Klutho PJ, Scott JA, Xie L, Luczak ED, Dibbern ME, Prasad AM, Jaffer OA, Venema AN, Nguyen EK, Guan X, Anderson ME, Grumbach IM. Oxidative activation of the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) regulates vascular smooth muscle migration and apoptosis. Vascul Pharmacol. 2014 Feb;60(2):75-83. doi:10.1016/j.vph.2014.01.001. Epub 2014 Jan 10. PubMed PMID: 24418021; PubMed Central PMCID: PMC3955051.

Scott JA, Klutho PJ, El Accaoui R, Nguyen E, Venema AN, Xie L, Jiang S, Dibbern M, Scroggins S, Prasad AM, Luczak ED, Davis MK, Li W, Guan X, Backs J, Schlueter AJ, Weiss RM, Miller FJ, Anderson ME, Grumbach IM. The multifunctional Ca²⁺/calmodulin-dependent kinase IIδ (CaMKIIδ) regulates arteriogenesis in a mouse model of flow-mediated remodeling. PLoS One. 2013 Aug 8;8(8):e71550. doi:10.1371/journal.pone.0071550. eCollection 2013. PubMed PMID: 23951185; PubMed Central PMCID: PMC3738514.

Honors and Awards

  • Graduate College Post-Comprehensive Award