*Columbia Genome Center
FY 1995 $500,000
FY 1996 $750,000
FY 1997 $750,000 |
|
Project Description and Goals: The Columbia Genome
Center (CGC) is a consortium of Columbia
University scientists and their laboratories working together for the
purposes of gene discovery and technology development related to the human
genome. Integrated genomic mapping and sequencing is being used to facilitate
gene discovery and gene therapy strategies. The aim is to encourage the
rapid clinical application of new developments by providing all areas of
expertise and resources that are necessary for the development of novel
diagnostics and therapeutics. It is anticipated that the Center will promote
new developments in clinical genetics and molecular medicine and contribute
significantly to genetic analysis in all branches of basic biology, including
molecular biology of development, differentiation, speciation and ecology.
The goal is to eventually bring the various laboratories together under
one roof. The Center’s Board of Advisors also works to promote the importance
of gene discovery in a manner understandable to the general public, works
with pharmaceutical companies interested in the financing of the search
for specific genes, and advises on ethical and social issues incumbent
in gene discovery.
Status and Accomplishments
FY 1995: SIP funding contributed to the acquisition
of equipment and other start-up related efforts. A proposal was submitted
to the NIH for the Human
Genome Project.
FY 1996: The CGC assembled all of the laboratories
and technologies needed to pursue its goals, including: Molecular Genetics
under Conrad
Gilliam, Physical Mapping under Stuart G. Fisher, DNA Sequencing under
James J. Russo, Cancer Genetics under Riccardo
Dalla-Favera, Genomic Informatics under Peisen Zhang, and Molecular
Bioinformatics under Barry
Honig. Two affiliated laboratories have been recruited; Cytogenetics
under Dorothy
Warburton and Animal Models of Human Diseases under Argiris
Efstratiadis. In FY 1996, the CGC completed a high resolution map of
human chromosome 13, an ultra-fine map of the human breast cancer locus
(BRCA2) on chromosome 13, an extended characterization of the Zinc ATPase
in follow-up to the discovery of the Wilson’s Disease Copper-ATPase, and
98% complete sequence and annotation of the Kaposi’s Sarcoma Herpesvirus
genome.
FY 1997: In FY 1997, 12 gene discovery projects
have been added to the Columbia Genome Center. The following is a representative
sample of recent research accomplishments:
-
Chromosome 6q harbors a tumor suppresser implicated in a
variety of cancers, including breast and lymphoma. The gene involved has
been mapped to a 70,000 base pair segment and the DNA sequence of this
locus has been completed to 99.95% accuracy. This extended sequence is
now being used to identify the gene and the mutations that result in carcinogenesis.
-
A region on chromosome 13,300,000 base pairs in length has
been identified and mapped as the locus of a gene implicated in Chronic
Lymphatic Leukemia. A highly annotated physical map of this region has
been constructed and is being used as a framework for DNA sequencing and
mutation analysis.
-
A novel hypothesis is being explored in the pathogenesis
of the most common solid tumor in children, Wilm’s Tumor. The mapped region
contains a number of imprinted genes one of which may be the basis for
the disease. The Center recently identified two new imprinted genes in
this locus, one of which is an active candidate in Wilm’s Tumor.
-
Substantial progress has been made in extending the genetic
map of kindreds with a high incidence of Manic-Depression. These maps are
being assembled at an unprecedented rate compared to our earlier efforts.
To realize its full potential, the CGC is now consolidating
and expanding its complement of laboratories, and has secured multi-year
operational funding. The former is being accomplished by moving three laboratories,
molecular genetics/genotyping, physical mapping, and statistical genetics,
and most of the administration of the CGC into 11,500 sq. ft. of new space
on the 5th floor of the new Berrie Pavilion. This move will be completed
in October, 1997. The 4th floor of this building is under construction
and will house most of the remainder of the CGC, including DNA sequencing,
genomic informatics, part of the molecular bioinformatics group, and the
rest of the administrative offices of the CGC. The move to the 4th floor
is scheduled for August, 1998. Occupancy of these two floors (a total of
23,000 sq.ft.)will consolidate almost all of the laboratories of the CGC
in the Berrie Pavilion. Plans are also underway to assign the 3rd floor
of the Pavilion to the Cancer Genetics Division of the Department of Pathology.
This would bring the CGC Section on Cancer Genetics under the direction
of Dr. Dalla Favera into proximity with the rest of the CGC. It would also
promote our ongoing collaborations with other members of the Division of
Cancer Genetics, including Drs.
B. Tycko and R. Parsons.
In March 1997, the CGC entered into a contract with VIMRx
Genomics, Inc. which provides $30,000,000, distributed over a five year
period (1/1/97 to 12/31/2002). Of this amount, the CGC receives direct
funding of $22,500,000 and Columbia receives $7,500,000. These funds are
being used to prosecute a range of disease gene discovery projects, including
chronic lymphatic leukemia, non-Hodgkins lymphoma, breast cancer, multiple
myeloma, Wilm’s tumor, progressive familial epilepsy, adult-onset glaucoma,
bipolar disorder (manic-depression), and radiation toxicity (breast cancer
and prostate cancer).
The CGC participates actively in applications for funding
from a variety of agencies, especially the NIH. The Center is currently
awaiting the decision on a PO1 application on Tumor Suppressers, sent to
the NIH, with Dr. R. Dalla Favera as the Principle Investigator. Plans
are also underway on sending an application to the NIH, to map and sequence
the Legionella genome, in collaboration with Dr.H.Shuman.
Project Leader: Isidore
Edelman, Robert W. Johnson Professor, Biochemistry and Molecular Biophysics