Maegen A. Ackermann Borzok, Ph.D.
Department: Physiology and Cell Biology
Campus Address: Graves Hall rm 5198, 333 W. 10th Ave
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
Research in our lab focuses on cytoskeletal and structural elements of cardiac muscle necessary to maintain beat-to-beat synchrony and normal cardiomyocyte coupling with the overall objective of understanding the mechanisms of select cardiomyopathies and human cardiac arrhythmias. The goals of our program are threefold:
1. to define novel mechanisms of cardiac dysfunction
2. to understand the link between structural proteins and the development of pathological mechanisms
3. to define novel signaling mechanisms linking cytoskeletal proteins and cardiomyocyte dysfunction
Current projects in the lab include:
1. Elucidating novel mechanisms of arrhythmogenic cardiomyopathy linked to clinical variants of desmoplakin.
Using a patient-specific approach we focus on developing a targeted therapy through understanding the precise molecular pathology of select clinical variants. Using a directed bilateral in silico and in vitro workflow we can bin clinical variants based on their susceptibility to calpain-mediated degradation. Using iPSC and engineered heart tissue along with mouse models we are assessing functional phenotypes of the binned variants.
1. Understanding the role that an imbalance of obscurin polypeptides plays in cardiac dysfunction.
Obscurin polypeptides are a family of multifunctional cytoskeletal proteins that function as molecular scaffolds through their structural domains and mediate signaling through their signaling motifs. Using human heart explants, we identify a decrease in giant obscurins but an increase in small signaling obscurins in failing hearts compared to donor controls. This phenomenon of an imbalance of obscurin polypeptides has also been observed in other disease states, including, obscurin-linked cardiomyopathies and select cancers. Using biochemical in vitro assays and in vivo transgenic models we are elucidating the mechanisms of obscurin polypeptide imbalance.
- Ackermann MA.*, Petrosino JM., Manring HR., Wright P., Shettigar V., Kilic A., Janssen PML., Ziolo MT., Accornero F.* “TGF-β1 affects cell-cell adhesion in the heart in an NCAM-dependent mechanism.” J Mol Cell Cardiol. 112:49-57. 2017.
- Ackermann, MA*., King, B., Lieberman, NAP., Bobbili, PJ., Rudloff, M., Berndsen, CE., Wright, NT., Hecker, PA., Kontrogianni-Konstantopoulos, A.* “Novel obscurins mediate cardiomyocyte adhesion and size via the PIEK/AKT/mTOR signaling pathway.” J Mol Cell Cardiol. 111:27-39. 2017.
- Hu LR*., Ackermann MA*., Hecker PA., Prosser BL., King B., O'Connell KA., Grogan A., Meyer LC., Berndsen CE., Wright NT., Jonathan Lederer W., Kontrogianni-Konstantopoulos A. “Deregulated Ca2+ cycling underlies the development of arrhythmia and heart disease dues to mutant obscurin.” Science Advances. 3(6). 2017.
- 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., 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.
- 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.
*denotes equal contribution