STRUCTURE AND FUNCTION OF MYB ONCOGENE IN NEURONAL CELLS

  • Press, Richard (PI)

Project: Research project

Project Details

Description

As I have long been committed to a career as an academic biomedical
researcher, a primary factor in my choice of pathology as a specialty was
its substantial research opportunities. Despite my strong scientific
background, the three and one half years I have spent in clinical service
have left me in need of additional research training before attempting
an academic career on my own. Having finished the clinical phase of my
pathology residency, I am now devoting essentially all of my time to
continuing my inquiries into the molecular basis of tumorigenesis. In both fetal brain in vivo, and retinoic acid-treated neuroblastoma in
vitro, neuronal differentiation is accompanied by a significant decrease
in the expression of the c-myb oncogene. This decline of c-myb RNA
precedes both growth cessation and loss of phenotypic transformation,
implying a potential biologic role for this gene product. Our
preliminary observation of a neuroblastoma cell c-myb protein that is
larger in size than its hematopoietic cell counterpart suggests a
possible neuron-specific structural alteration. The experiments proposed
here are designed to: 1) characterize the structure of this
alternatively-sized neuronal myb protein, and 2) determine its function
in the processes of neuronal cell growth, differentiation and
tumorigenicity. Structural studies will involve cloning the c-myb cDNA
from both normal fetal brain and human neuroblastomas as well as RNase
protection, RNA-PCR, and immunoprecipitation. C-myb function will be
assessed by measuring proliferation, differentiation, and transformation
of neuroblastoma cells in which c-myb has either been artificially
inhibited or induced. In addition, c-myb expression will be examined in
neural tissue from developing rat embryos and from human-neural
crest-derived tumors. These studies should allow a characterization of
the amount, location,and timing of c-myb expression during the maturation
and transformation of neuronal cells both in vitro and in vivo. Although these aims are ambitious, the structural studies in particular
should be hastened by the substantial expertise of this lab in all areas
of molecular biology. Innumerable technical and intellectual benefits
should result from my association with this highly successful research
team. The productive nature of the entire lab environment will serve as
an excellent role model upon which to base my plans for an academic
career as an independent biomedical scientist.
StatusFinished
Effective start/end date7/1/916/30/94

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Neuroscience(all)

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