with puberty. Genetic analyses of the children of 
FHC probands has confirmed the difficulty of clini- 
cal diagnosis of FHC in children. Approximately 
50% of FHC in North America results from ;0-cardiac 
myosin heavy-chain missense mutations, and early 
genetic diagnosis will be useful to patients and 
physicians. 
The research carried out in the laboratory of In- 
vestigator Bernardo Nadal-Ginard, M.D., Ph.D. 
(Children's Hospital, Boston) is directed toward un- 
derstanding how the contractile apparatus of mam- 
malian cells is produced and regulated. These cells 
and their contractile apparatus are responsible for 
the structure and function of skeletal muscle and 
the cardiovascular system. First, the group seeks to 
identify and characterize genes responsible for the 
activation and repression of other genes that are re- 
sponsible for the production of the building blocks 
of the contractile system, the contractile proteins. 
Second, they wish to understand why muscle cells 
have lost the ability to divide and, therefore, to re- 
generate after an injury such as a myocardial infarc- 
tion. Third, they are exploring the basic mecha- 
nisms that allow a single gene to produce several 
different proteins that, in many cases, can have quite 
different functional properties. 
MyoD activates what appears to be the entire pro- 
gram for muscle cell differentiation when its ex- 
pression is experimentally forced in a number of 
cell types. Investigator Harold M. Weintraub, M.D., 
Ph.D. (Fred Hutchinson Cancer Research Center) 
and his colleagues have focused on how MyoD acti- 
vates the hundreds to thousands of genes responsi- 
ble for making a muscle cell, and how MyoD is acti- 
vated during development. They have obtained 
evidence for a new type of regulatory element — a 
protein that recognizes that MyoD has bound to the 
proper DNA site by interacting with both the MyoD 
protein and the MyoD DNA-binding site. The group 
will continue their studies of MyoD expression in 
development of frogs and worms, focusing on classi- 
cal embryological approaches in the former and ge- 
netic approaches in the latter. In frog development, 
MyoD transcription is first activated throughout the 
entire blastula, only to be stabilized in presumptive 
mesoderm when induction occurs. In worms, MyoD 
is activated when a cell first becomes committed 
solely to the muscle lineage, and this requires only 
500 base pairs of the upstream MyoD control region. 
The laboratory of Associate Investigator Rebecca 
A. Taub, M.D. (University of Pennsylvania) is study- 
ing the molecular biology of liver growth by charac- 
terizing the response as the liver initiates regenera- 
tion immediately after partial hepatectomy. Under 
study are a particular growth factor-like molecule 
that may play a major role in coordinating the 
growth of multiple hepatic cell types during liver 
development and regeneration, proteins that regu- 
late the genes expressed in regenerating liver, and 
proteins that regulate signals transmitted in hepatic 
cells. 
Senior Investigator Philip Leder, M.D. (Harvard 
Medical School) and his colleagues have directed 
their efforts toward understanding malignant dis- 
ease at the genetic level. In studies that often in- 
volve the use of transgenic (or genetically engi- 
neered) mice, the group examines the action of 
genes not just in cells, but in the organism as a 
whole. Recent work has focused on factors that mod- 
ify tumorigenesis by either provoking or inhibiting 
tumor formation. Particularly important have been 
discoveries regarding the potent antitumor effects 
of a biologically active product of the immune sys- 
tem, interleukin-4. These studies have also shed 
light on the fundamental process of development in 
the mammalian embryo and the developing immune 
system. 
The aim of the laboratory of Associate Investigator 
Andrew P. Feinberg, M.D., M.P.H. (University of 
Michigan) is to identify tumor suppressor genes on 
human chromosome 1 1 . The group has found that at 
least two genes on chromosomal band llpl3 are 
involved in Wilms' tumor (WT) , a childhood kidney 
cancer. They have shown the existence of a second 
WT gene on band llpl5, which appears to be 
involved in many common adult cancers. Also 
localized to this band is the hereditary disorder 
Beckwith-Wiedemann syndrome, which causes Wilms' 
and other childhood cancers. A novel strategy for 
identifying and isolating tumor suppressor genes 
has been developed that may have application to 
other areas of genetics, including efforts to clone 
genes involved in cellular aging. Through this new 
approach a subchromosomal fragment from 1 lpl5 
has been isolated, which causes cessation of growth 
when transferred into tumor cells. 
The laboratory of Assistant Investigator Vikas P. 
Sukhatme, M.D., Ph.D. (University of Chicago) stud- 
ies transcription factors in two different contexts. 
They have isolated and characterized genes induced 
by mitogenic signals. Some of these genes are stimu- 
lated in every mammalian cell type tested. Impor- 
tantly, the proteins encoded by these genes encode 
transcription factors containing zinc finger motifs, 
thereby regulating transcription of a distal set of 
genes. These proteins therefore serve as nuclear sig- 
nal transducers. Their expression is modulated in a 
wide range of biological processes in addition to 
cellular proliferation. Recently, Dr. Sukhatme's lab- 
oratory has identified similar genes expressed in the 
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