Laboratory of Molecular and Developmental Biology

Building 7, Room 100
7 Memorial Drive, MSC 0704
Bethesda, Maryland 20892-0704
Phone: (301) 496-4343
Fax: (301) 402-0781

• Mission
• Structure

Mission Statement

Overall, the Laboratory of Molecular and Developmental Biology (LMDB), headed by Dr. Joram Piatigorsky, comprises four Sections that conduct basic research on cellular and molecular aspects of the eye. Much of the LMDB research concerns development, evolution and glaucoma. The focus is on the expression and function of genes. Eye tissues under investigation include lens, cornea, trabecular meshwork and retina. A brief overview of interests of the Sections is given below; more detailed information is supplied with the specific Sections.

The Section on Molecular Genetics (SMG) is directed by Dr. Joram Piatigorsky; the research in this Section centers on gene expression in the lens and cornea. Particular attention is given to the diverse lens crystallins, especially small heat shock protein/aB-crystallin, and the abundant water-soluble corneal proteins. Research by the SMG concentrates on understanding the molecular mechanisms of gene expression and the numerous function(s) of the encoded proteins. Global gene expression during corneal development is also being investigated via serial analysis of gene expression (SAGE) and microarrays. These analyses are providing molecular signatures of cornea, revealing the dynamics of gene expression during corneal development, and identifying genes of interest for further study to understand normal and diseased cornea. Humans, mice, zebrafish and jellyfish are being investigated, giving an evolutionary perspective to the work.

The research in Dr. Ana Chepelinsky's group, formally a part of the SMG, operates independently and is directed toward understanding the mechanisms involved in the regulation of gene expression in the eye, with emphasis on the lens. An area of major interest is lens fiber membrane channel proteins. Much of the research in this group is focused on MIP/aquaporin 0. MIP/aquaporin is the major intrinsic protein of the lens fiber membrane; moreover, it is expressed specifically in the ocular lens fibers. Signaling pathways under investigation include the regulation of the transcriptional activation of the MIP/aquaporin 0 gene during differentiation of the lens epithelial cells into fibers, the translocation of MIP/aquaporin O to the plasma membrane, and the recruitment of soluble proteins to plasma membrane. The study of MIP/aquaporin 0 contributes to the understanding of gene expression required for normal lens development and homeostasis essential for lens transparency.

The Section of Molecular Mechanisms of Glaucoma (SMMG) is directed by Dr. Stanislav Tomarev; it conducts basic research on glaucoma, one of the leading causes of blindness in the world. Recent studies have focused on the development of novel mouse models of glaucoma. Another main area of research is the identification of new genes responsible for glaucoma as well as those important for normal eye development and function. Several novel genes were identified that are expressed in different eye structures. One encodes a novel olfactomedin domain-containing protein that was named optimedin. Functions of optimedin and other olfactomedin-containing genes in the eye are under study.

The Transgenic Animal and Genome Manipulation Section (TAGMS) is directed by Dr. Eric Wawrousek; it performs both research and service functions. This Section is the home of the NEI Central Transgenic Facility, which provides, to NEI researchers, intellectual and technical expertise for the generation and maintenance of transgenic and gene knockout mouse lines. Research activities involve the use of genetically altered mice to probe ocular development, function and disease. The Section has been particularly interested in small heat shock proteins, members of the alpha-crystallin family, which are abundantly expressed in the eye, and perform many protective functions in ocular tissues, as well as many other tissues of the body. The TAGMS also investigates new methodologies for introducing point mutations into the mouse genome, to advance the field, and make genetic modeling in the mouse easier and more available to researchers.

The Section on Cell Differentiation (SCD) is directed by Dr. Peggy Zelenka; it studies signaling mechanisms that regulate adhesion, proliferation and differentiation in epithelial cells of the lens and cornea. A major focus of the SCD is to determine the function of the protein kinase, Cdk5, in the lens and cornea. Previous studies have shown that Cdk5 regulates cell-matrix and cell-cell adhesion in both tissues, while more recent work has concentrated on determining the mechanism of these effects. The SCD explores these questions in cultured cells and in animal models, including transgenic mice and mice with homozygous gene deletions. Current results indicate that Cdk5 affects cell adhesion by modulating the subcellular localization and activity of Src, a tyrosine protein kinase involved in cytoskeletal regulation. Src activity promotes focal adhesion turnover, stimulates cell migration, and disrupts cadherin-dependent cell-cell adhesion. By limiting Src activity, Cdk5 maintains the balance between focal adhesion formation and disassembly, and prevents disruption of the epithelial cell sheet during wound healing. In search of other clues about Cdk5 function, the laboratory has used yeast two hybrid screening to identify a specific interaction between the Cdk5 activator, p39, and muskelin, a protein thought to be involved in adhesion and signaling. Future experiments will address the significance of Cdk5 activity and of the p39-muskelin interaction in the cell movements that accompany embryogenesis, differentiation, and wound healing.

Structure

The Laboratory of Molecular and Developmental Biology Office is composed of the following staff:

The Laboratory of Molecular and Developmental Biology is composed of the following Sections: (Click on the name of the Section to see its home page)

Section:	Chief:	E-mail:	Phone:
Molecular Genetics	Joram Piatigorsky, Ph.D.	joramp@nei.nih.gov	(301) 496-9467
Cellular Differentiation	Peggy S. Zelenka, Ph.D.	zelenkap@nei.nih.gov	(301) 496-7490
Transgenics and Genome Manipulation	Eric Wawrousek, Ph.D.	wawrouseke@nei.nih.gov	(301) 496-8841
Molecular Mechanisms of Glaucoma	Stanislav Tomarev, Ph.D	tomarevs@nei.nih.gov	(301) 496-8524