relative deficiency of insulin, it seems likely that de- 
creased levels of this glucose transporter contribute 
to the increased blood glucose levels that are an 
important clinical feature of diabetes. 
The laboratory of Associate Investigator Rebecca 
A. Taub, M.D. (University of Pennsylvania) is explor- 
ing three main areas of interest. 1) The genes and 
proteins that are expressed in liver cells immedi- 
ately after the initiation of hepatic regeneration are 
being examined. Some of these genes may be re- 
sponsible for the many subsequent steps occurring 
within a cell that result in cellular proliferation. 
2) The laboratory is studying how the level of the 
insulin receptor gene expression is controlled 
within cells. In some diabetic conditions, decreased 
numbers of cellular insulin receptors may contrib- 
ute to the diabetes. Knowing what controls the 
level of insulin receptors on a normal cell will facili- 
tate understanding receptor abnormalities in diabe- 
tes. 3) The molecular makeup of antibodies di- 
rected against a receptor on platelets involved in 
blood clotting has been analyzed to learn about the 
region of the fibrinogen protein that normally 
binds to the platelet receptor. 
Assistant Investigator Andrew E Feinberg, M.D., 
M.EH. (University of Michigan) and his colleagues 
are investigating the molecular genetics of human 
cancer and report progress in two areas of cancer 
genetics. The first involves alterations in DNA meth- 
ylation, a modification of the nucleic acid cytosine 
in DNA that may play an important role in both 
normal gene regulation and the abnormal regula- 
tion that characterizes cancer. A novel system was 
developed for capturing cells in which the DNA is 
hypomethylated, but before the cells have become 
malignantly transformed. The laboratory has begun 
to identify genes that mediate the role of altered 
DNA methylation in carcinogenesis, as well as some 
of the earliest changes in gene expression in cancer. 
Second, the laboratory has localized tumor sup- 
pressor genes in several types of human cancer. 
Using molecular methods, they have identified sev- 
eral genetic alterations that may mediate the multi- 
ple steps in the development of colon and rectal 
cancer. They have also identified the location of the 
gene for Beckwith-Wiedemann syndrome, a disor- 
der of abnormal growth that predisposes to several 
solid tumors of childhood. This gene is also in- 
volved in the progression of childhood and adult 
malignancies. 
Research of Assistant Investigator Laimonis A. 
Laimins, Ph.D. (The University of Chicago) centers 
on the molecular biology of human papil- 
lomaviruses. Human papillomavirus (HPV) types 16 
and 18 have been implicated as the causative 
agents of cancers of the cervix and penis. In vitro 
transformation studies have identified a new viral 
transforming gene E7 that together with the E6 
gene product may play a principal role in the in- 
duction of cervical intraepithelial neoplasias by 
these viruses. In vitro alteration of differentiation is 
assayed in a system where epithelial cells are grown 
at an air- to-liquid interface, and papillomaviruses 
were observed to induce morphological changes 
similar to those seen in genital intraepithelial neo- 
plasias in vivo. To examine the tissue tropism of 
HPV viruses. Dr. Laimins and his colleagues have 
studied the transcriptional regulatory mechanisms. 
Three distinct enhancer elements have been identi- 
fied that may play different roles in the life cycle of 
these viruses. Furthermore, viral transactivators 
from herpes simplex virus, as well as a phorbol 
ester, have been shown to be capable of increasing 
papillomavirus expression. Studies are continuing 
on the structure and function of the viral proteins, 
as well as on a transgenic mouse model for HPV- 
induced malignancies. 
Research in the laboratory of Assistant Investiga- 
tor Donna L. George, Ph.D. (University of Pennsyl- 
vania) has led to the identification of one gene, and 
possibly another, with a potential for altering cellu- 
lar growth patterns. In one case the introduction 
and subsequent overexpression of the gene in ap- 
propriate recipient cells results in a distinctive 
change in morphology characteristic of transformed 
cells. In the second case, a different expression pat- 
tern in transformed cells versus nontransformed 
cells may reflect a central role for this gene in some 
pathways of tumorigenesis. Progress also has been 
made in identifying DNA sequence elements impor- 
tant for the expression of the cKi-ras proto- 
oncogene and in isolating cDNA clones encoding 
their cognate DNA-binding proteins. 
Growth factors induce a genetic program in tar- 
get cells. Among the genes initially activated are 
several that encode known or probable transcrip- 
tion factors that are thought to regulate the genetic 
program, including Nur77, a new member of the 
steroid/thyroid hormone receptor family; Zif268, a 
zinc finger protein; and two members of the Jun 
family, c-Jun and Jun-B. Zif268 has been shown by 
Senior Investigator Daniel Nathans, M.D. (The 
Johns Hopkins University) and his associates to be 
a sequence-specific DNA-binding protein, and its 
consensus binding site has been defined. Jun-B, 
c-Jun, and a newly discovered member of the jun 
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