Aladin M Boriek
Aladin M Boriek
- Research Interests
Professional StatementMechanical signal transduction
We have been interested in the anisotropic regulation of the mechanosensitive genes, the Ankrd2. We found that axial stretch activated Akt, which up-regulated Ankrd2 expression through NF-kappaB. However, stretch in the orthogonal direction to the muscle fibers activated Ras-GTP, Raf-1, and Erk1/2 proteins, which up-regulated Ankrd2 expression through AP-1. Our data show the anisotropic regulation of Ankrd2 gene expression in the diaphragm muscles occurs via two distinct mechanosensitive signaling pathways. This work was conducted in collaboration with my colleague Dr. Junaith Mohamed, a Research Associate in the Department of Medicine, and a member of our research group.
We have been interested in the physiologic role of Sirt1 in skeletal muscles. We have recently unraveled a mechanism of transcription regulation of the Sirt1 gene by the EGR1 (early growth response factor 1), which occurs in response to mechanical stretch. This stretch-responsive gene activation program is required to eliminate ROS generated during stretch. This work was conducted in collaboration with my colleague Dr. Patricia Pardo, a Research Associate in the Department of Medicine, and a member of our research group. Assessment of respiratory muscle function in mouse models of muscular dystrophy
A complex rearrangement mutation in the mouse titin gene leads to an in-frame 83-amino acid deletion in the N2A region of titin. Autosomal recessive inheritance of the titin muscular dystrophy with myositis (Ttn(mdm/mdm)) mutation leads to a severe early-onset muscular dystrophy and premature death. We have tested the hypothesis that the titin N2A deletion in the mdm mouse diaphragm would have a deleterious impact on the force-generating capacity and altered passive mechanical properties, independent of major histopathology. Our data show significant structural and functional aberrations of the respiratory pump in the mdm mouse that may be attributable to a critical function of titin's N2A region. This work was part of the PhD thesis of Dr. Michael Lopez who has been a member of our research group. Modeling and assessing diaphragm mechanics
Investigation of the determinants of diaphragm muscle mechanics and kinematics, including the unique mechanical properties of the diaphragm and structural issues such as the geodesic properties of diaphragm muscle fibers. Current works describe numerous approaches to dealing with these determinants, including measuring diaphragm curvature, displacement and muscle shortening, as well as computational modeling of the effect of muscle anisotropic properties on diaphragm shape. This work is established in collaboration with Drs. Rolf Hubmayr at Mayo Clinic.
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