Faculty > HODZIC

Didier Hodzic, Ph.D.

Assistant Professor, Ophthalmology and Visual Sciences
E-mail: Hodzicd@vision.wustl.edu
(314) 362-7037 (office)

(314) 362-6800 (lab)

B.S. Biochemistry, University of Liege, Belgium (1991)

Ph.D., Molecular Oncology, University of Liege, Belgium(1999)

Fellow, Cell Biology, Washington University School of Medicine (2000-2005)

Research Assistant Professor, Cell Biology, Washington University School of Medicine (2006-2008)

 

Research Area:

Retina

Research Interests:

My laboratory focuses on LINC complexes (Linkers of the Nucleoskeleton to the Cytoskeleton), a family of macromolecular assemblies of the nuclear envelope that physically connects the nucleus to the surrounding cytoskeleton. LINC complexes assemble through the interaction between two families of proteins:

1) Sun proteins, a family of inner nuclear membrane (INM) proteins whose N-terminal region

protrudes in the nucleoplasm interacts with the nuclear lamina.

2) Nesprins, a family of outer nuclear membrane (ONM) proteins whose N-terminal region interacts with cytoskeletal components such as actin and plectin.

It is within the perinuclear space between the INM and ONM that C-terminal evolutionary-conserved domains of both Sun proteins and Nesprins interact directly to connect the nuclear lamina to the cytoskeleton.

In lower organisms, LINC complexes are involved in nuclear migration and anchorage. Using various approaches to disrupt endogenous LINC complexes in cell culture and in vivo transgenic mouse models, my laboratory investigates the role of LINC complexes in nucleokinesis of various mammalian neurons. Because retinogenesis requires the coordinated migration of different types of neurons and their ensuing spatial positioning (3 distinct nuclear layers!) to form a fully functional laminated retina, we mostly use the mouse retina as our main model. The use of time-lapse video microscopy coupled to primary neurons and organotypic culture systems as well as the development of nucleokinesis assays both in vivo and in vitro will provide new insight into the molecular mechanisms the physiological significance of nuclear dynamics in the CNS.

Selected Publications:

  1. Hale, C.M., Shrestha A.L., Khatau, S.B., Stewart-Hutchinson, P.J., Hernandez, L., Stewart, C.L., Hodzic, D. and Wirtz, D. Dysfunctional connections between the nucleus and the actin and microtubule networks in laminopathic models. Biophysical J. 95:5462-75 (2008).

  2. Stewart-Hutchinson, P.J, Hale, C.M., Wirtz D., Hodzic, D. Structural requirements for the assembly of LINC complexes and their function in cellular mechanical stiffness. Exp. Cell Res. 31:1892-1905 (2008).

  3. Lee, J.S.H., Panorchan, P., Hale, C.M., Khatau, S.B., George, J., Stewart, C.L., Hodzic, D., Wirtz, D. Effects of Nuclear lamin A/C deficiency on cell mechanics, polarization and migration. Biophysical J. 93: 2542-2552 (2007).

  4. Crisp, M., Liu, Q., Roux, K., Rattner, J.B., Shanahan, C., Burke, B., Stahl, P.D., Hodzic, D.  Coupling of the nucleus and cytoplasm:  role of the LINC complex.   J. Cell Biol. 172: 41-53 (2006)

  5. Hodzic, D., Yeater, D.B., Bengtsson, L., Otto, H. & Stahl, P.D. Sun2 is a novel mammalian inner nuclear membrane protein. J. Biol. Chem. 279: 25805-25812 (2004).

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