PROGRAM IN CELL BIOLOGY AND REGULATION 
The Program in Cell Biology and Regulation is 
largely concerned with the structure and biology of 
individual cells, the factors that regulate their nor- 
mal growth and distinctive functions, and the ways 
in which cells interact with each other. It is a contin- 
uation of the Institute's oldest research program. 
Formed in 1976 as the Metabolic Regulation Pro- 
gram, it was renamed in 1985 to reflect the Insti- 
tute's growing research activity in the area of molec- 
ular cell biology. 
Investigators working in this program are located 
at the University of California at Berkeley, at Los An- 
geles, at San Diego, and at San Francisco; the Univer- 
sity of Southern California at Los Angeles; Stanford 
University; the University of Colorado at Boulder; 
the University of Colorado Health Sciences Center at 
Denver; Yale University; the University of Chicago; 
Northwestern University in Evanston; the University 
of Iowa College of Medicine in Iowa City; the Johns 
Hopkins University; the Carnegie Institution of 
Washington at Baltimore; the University of Massa- 
chusetts at Worcester; Brigham and Women's Hospi- 
tal in Boston; Massachusetts General Hospital; Tufts 
University School of Medicine in Boston; the Massa- 
chusetts Institute of Technology; the University of 
Michigan Medical School; Washington University 
School of Medicine in St. Louis; Princeton Univer- 
sity; Cold Spring Harbor Laboratory; Rockefeller 
University; Memorial Sloan-Kettering Cancer Center 
in New York City; Cornell University Medical Col- 
lege in New York City; Duke University School of 
Medicine; Oklahoma Medical Research Foundation 
in Oklahoma City; the University of Pennsylvania; 
St. Jude Children's Research Hospital in Memphis; 
Vanderbilt University; the University of Texas South- 
western Medical Center at Dallas; Rice University; 
the University of Washington at Seattle; and the Uni- 
versity of Wisconsin-Madison. 
Research of Investigator G. Vann Bennett, M.D., 
Ph.D. (Duke University) and his colleagues has fo- 
cused on the structure, regulation, and identifica- 
tion of the nearest neighbors of ankyrins, a family of 
structural proteins strategically located on the cyto- 
plasmic surface of the plasma membrane with recog- 
nition sites for both membrane-spanning integral 
proteins and cytoplasmic structural proteins. A ma- 
jor class of ankyrin-binding proteins has been identi- 
fied in adult rat brain and determined to be related 
closely to a membrane-spanning neural cell adhe- 
sion molecule in the immunoglobulin superfamily 
previously implicated in axonal bundling in devel- 
opment of embryonic brain. A physiological conse- 
quence of the convergence of cytoskeletal, trans- 
membrane, and intercellular connections in adult 
brain may be stabilization of the structure of the 
nervous system so that this intricate arrangement of 
cells can survive the traumas of everyday life. 
Cells in the body are attached to adhesive proteins 
via the cell surface receptors called integrins. This 
attachment is vital for proper cell function; plays 
important roles in embryogenesis, hemostasis, and 
wound healing; and is aberrant in thrombosis and 
cancer. The laboratory of Investigator Richard O. 
Hynes, Ph.D. (Massachusetts Institute of Technol- 
ogy) studies several of the adhesive proteins, espe- 
cially the fibronectins. In the past year the group has 
made progress in 1) developing strains of mice with 
alterations in genes encoding fibronectins and inte- 
grins, and another adhesive protein, P-selectin, in- 
volved in inflammation; 2) analyzing the roles in 
embryonic development of integrins and fibronec- 
tins in both fruit flies and mice; 3) understanding 
the regulation of expression and function of these 
proteins; and 4) analyzing the nature of connections 
between fibronectins, integrins, and the cytoskele- 
ton. The laboratory continues to study the molecu- 
lar details of these proteins and their roles in normal 
physiology and abnormal pathology. 
Vascular endothelial cells form a nearly continu- 
ous cobblestone-like lining of blood vessels 
throughout the body. The laboratory of Associate In- 
vestigator Michael P. Bevilacqua, M.D., Ph.D. (Uni- 
versity of California, San Diego) studies the mecha- 
nisms by which leukocytes (white blood cells) bind 
to the vascular endothelium. Although beneficial in 
fighting infection and in wound healing, this bind- 
ing process can contribute to human disease under 
certain conditions, such as in heart attacks, acute 
lung injury, and rheumatoid arthritis. One group of 
molecules that support the binding of leukocytes to 
the endothelial lining are the selectins. E-selectin is 
displayed on the surface of endothelium at sites of 
inflammation and binds to sugars on the surface of 
leukocytes. Dr. Bevilacqua's laboratory is using 
synthetic sugars to assess binding to selectins di- 
rectly and to identify anti-inflammatory therapeutic 
agents. In a related project, the eff'orts of the group 
have demonstrated that blood-borne tumor cells, in- 
cluding those derived from colon cancers and mela- 
nomas, may use endothelial adhesion molecules to 
spread to distant sites (metastasize). Eff'orts are 
under way to understand the molecular mechanisms 
of these processes, in the hope of identifying new 
anticancer therapies. 
CELL BIOLOGY AND REGULATION 5 
