Maegen A. Ackermann Borzok, Ph.D.
The Ohio State University Wexner Medical Center
Department of Physiology and Cell Biology
473 W. 12 Ave
Davis Heart and Lung Research Institute, rm 405B
Columbus, OH 43210
Education & Training:
Elizabethtown College, Elizabethtown, PA 2002, BS Biochemistry
University of Maryland, School of Medicine, Baltimore, MD 2007, PhD Biochemistry
University of Maryland, School of Medicine, Baltimore, MD 2008-2012, Postdoctoral Fellow
My research interests focus on the intricate structural organization and functionality of striated muscle physiology and pathophysiology, with a focus on the obscurin family of proteins. The obscurin family of cytoskeletal proteins is composed of giant (~800 kDa) and smaller (~40-250 kDa) isoforms that were originally identified in striated muscles, where they have known essential roles in cytoskeletal organization, myofibrillogenesis, and Ca2+ homeostasis. Obscurins’ distinct subcellular distributions and specific binding partners dictate the functions of individual isoforms.
Recently we have characterized two novel obscurin isoforms that localize to the cardiac intercalated disc (ID). The ID is a unique membrane microdomain that mediates coupling through protein-protein interactions and signal transduction between neighboring cells, allowing the synchronous beating of the heart. A disruption of ID complexes interrupts regular heart function and can lead to arrhythmias and heart disease.
With the recent advancement of innovative proteomic technologies, many new members of the giant ID proteome have been identified, including two novel obscurin isoforms. These obscurin isoforms localize to the ID where they interact with other ID proteins as well as specific phospholipids. Through their interaction with phospholipids, obscurins regulate the PI3 kinase, AKT, and mTOR signaling pathways, leading to down stream effects on cell aggregation and size, implicating obscurins in the prevention of cardiac hypertrophy. Using biochemistry and molecular biology with complementary in vivo studies and translation work our lab is currently investigating the mechanisms that novel obscurins play cardiac signaling and cell-cell coupling.
Additional research areas of interest for the lab include the intercalated disc proteome in health and disease and the role of novel obscurins in skeletal muscle signaling and atrophy.
- Ackermann, M.A., Kerr, J., Ward, C.W., and Kontrogianni-Konstantopoulos A. “The Phosphorylation Profile of Myosin binding protein-C Slow is Dynamically Regulated in slow twitch muscles in Health and Disease.” Scientific Reports. 2015.
- Ackermann, M.A., Ward, C.W., Gurnett, C., and Kontrogianni-Konstantopoulos A. “Myosin binding protein-C slow phosphorylation is Altered in Duchenne Dystrophy and Arthrogryposis Myopathy in fast twitch skeletal muscles.” Scientific Reports. 2015.
- Ackermann, M.A.*, Shriver, M.*, Perry, N.A.*, Hu, L.-Y.R. and Kontrogianni-Konstantopoulos, A. “Obscurins: Goliaths and Davids take over non-muscle tissues.” PLoS One. 9(2):e88162. 2014.
- Ackermann, M.A. and Kontrogianni-Konstantopoulos, A. “Myosin binding protein-C slow: a multifaceted family of protein with a complex expression profile in fast and slow twitch skeletal muscles.” Frontiers in Physiology. 4:391. 2013.
- Ackermann, M.A., Patel, P.D., Valenti, J., Takagi, Y., Homsher, E., Sellers, J.R., and Kontrogianni-Konstantopoulos A. “Loss of actomyosin regulation in distal arthrogryposis myopathy due to mutant myosin binding protein-C slow.” FASEB J. 27(8):3217-3228. 2013.
- Ackermann, M.A., Ziman, A., Strong, J., Zhang, Y., Hartford, A.K., Ward, C.W., Randall, W.R., Kontrogianni-Konstantopoulos, A., and Bloch, R.J., "Integrity of the network sarcoplasmic reticulum in skeletal muscle requires small ankyrin 1", J. Cell Sci. 124(Pt 21):3619-30. 2011.
- Ackermann, M.A., and Kontrogianni-Konstantopoulos, A. “Myosin Binding Protein C slow is a Novel Substrate for Protein Kinase A (PKA) and C (PKC) in skeletal muscle”, J. Proteome. Res. 10(10):4547-55. 2011
- Busby, B.R, Oashi, T., Willis, C.D., Ackermann, M.A., Kontrogianni-Konstantopoulos, A., MacKerell, A.D., and Bloch, R.J., “Electrostatic Interactions Mediate Binding of Obscurin to Small Ankyin 1: Biochemical and Molecular Modeling Studies”, J. Mol. Biol. 408(2):321-34. 2011.
- Busby, B.R, Willis, C.D., Ackermann, M.A., Kontrogianni-Konstantopoulos, A., and Bloch, R.J., “Characterization and Comparison of the Binding Sites on Obscurin for Small Ankyrin 1” Biochemistry. 49(46), 9948-56. 2010.
- Ackermann, M.A., Hu, L.Y., Bowman, A.L., Bloch, R.J. and Kontrogianni-Konstantopoulos, A., " Obscurin Interacts with a Novel Isoform of Myosin Binding Protein C at the Periphery of the Sarcomeric M-Band and Regulates Thick Filament Assembly", Mol. Biol. Cell. 20(12), 2963-78. 2009.
- Borzok, M.A., Catino, D.H., Nicholson, J., Kontrogianni-Konstantopoulos, A., and Bloch, R.J., "Mapping the Binding Site on Small Ankyrin 1 for Obscurin", J. Biol. Chem. 282(44), 32384-96, 2007.