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Structural and Computational Biology and Molecular Biophysics

Houston, Texas

A BCM research lab.
Structural and Computational Biology & Molecular Biophysics
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Aladin Boriek, Ph.D.

Aladin Boriek, Ph.D.

Professor, Medicine-Pulmonary

Baylor College of Medicine

Education:

Ph.D., Computational Mechanics, Rice University (1990)
Post-doctoral training, Respiratory muscle mechanics, Baylor College of Medicine (1992)

Research Interests:

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.

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.

Mechanical 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.

Selected Publications:

  • Pardo PS and Boriek AM. An autoregulatory loop reverts the mechanosensitive Sirt 1 induction by EGR1 in skeletal muscle cells. Aging (Albany NY), 4(7):456-61 (2012). PubMed
  • Mohamed JS and Boriek AM. Loss of desmin triggers mechanosensitivity and up-regulation of Ankrd1 expression through Akt-NF-kB signaling pathway in smooth muscle cells. FASEB J, 26(2):757-65 (2012). PubMed
  • Mohamed JS, Hajira A, Li Z, Paulin D and Boriek AM. Desmin regulates airway smooth muscle hypertrophy through early growth-responsive protein-1 and microRNA-26a. J Biol Chem, 286(50):43394-404 (2011). PubMed
  • Pardo PS and Boriek AM. The physiological roles of Sirt1 in skeletal muscle. Aging (Albany NY), 3(4):430-7 (2011). PubMed
  • Greybeck BJ, Wettergreen M, Hubmayr RD and Boriek AM. Diaphraghm curvature modulates the relationship between muscle shortening and volume displacement. Am J Physiol Regul Integr Comp Physiol, 301(1):R76-82 (2011). PubMed
  • Pardo PS, Mohamed JS, Lopez MA and Boriek AM. Induction of Sirt1 by mechanical stretch of skeletal muscle through the early response factor EGR1 triggers an antioxidative response. J Biol Chem, 286(4):2559-66 (2011). PubMed
  • Chu I, Fernandez C, Rodowicz KA, Lopez MA, Lu R, Hubmayr RD and Boriek AM. Diaphraghm muscle shortening modulates kinematics of lower rib cage in dogs. Am J Physiol Regul Integr Comp Physiol, 299(6):R1456-62 (2011). PubMed

For more publications, see listing on PubMed.

Contact Information:

Department: Medicine - Pulmonary
Address: Room 825E
Baylor College of Medicine
One Baylor Plaza
Houston, Texas 77030
Phone: 713-798-6091
Fax: 713-798-2050
E-mail: boriek@bcm.edu

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