Lemischka Lab
The laboratory of Ihor R. Lemischka is in the Department of Gene and Cell Therapy and
the Black Family Stem Cell Institute of Mount Sinai School of Medicine. The major interests of the laboratory
are focused on the biological regulation of stem cells. Traditionally,
the interests of the lab have been in the hematopoietic stem cell
system. More recently, a more general approach that includes embryonic
stem cells and neural stem cells has evolved. The laboratory uses whole
animal, cellular, molecular, genomic, and computational methodologies.
A major effort that is now nearing completion is the definition of
global molecular "parts lists" of stem cell populations. That is, the
laboratory has sought to identify most. if not all gene products that
are preferentially expressed in undifferentiated stem cells, but not in
their more mature progeny. The technologies employed involve
high-throughput DNA sequencing of subtracted cDNA libraries constructed
from highly enriched stem cells, as well as microarray analyses. A
major emphasis has been placed on in-depth bioinformatic analyses. The
current efforts of the laboratory are focused on developing ways to
assemble the "parts lists" into regulatory pathways and networks. The
strategies to facilitate this include inhibitory RNA technologies
interfaced with global gene expression analyses. Other more traditional
approaches include the production of transgenic animals, and engineered
mutations.
Moore Lab
Research in the Moore laboratory is focused on defining the
microenvironmental elements of the hematopoietic stem cell niche at the
cellular and molecular level. We are using a fetal liver-derived
stromal cell line, AFT024, as a surrogate system for the stem cell
niche. Previous studies have shown that AFT024 can maintain competitive
repopulating stem cell activity that is quantitatively identical to that
present in freshly purified stem cells. We suggest that the AFT024
stromal cell line provides a unique and positively acting molecular
milieu that maintains self-renewing stem cells. A subtracted cDNA
library enriched for gene products expressed by AFT024 was made and over
6000 cDNAs have been sequenced, informatically analyzed, and assembled
into the SCDb and a stand alone Stromal Cell Database
(http://stromalcell.princeton.edu).
We are using various strategies to
further characterize the cDNAs in this library, such as lentiviral
vector-mediated RNAi loss of function and retroviral vector-mediated
gain of function approaches in biological assays, RNA in situ studies,
and development of antibodies. Molecular cross-talk between stem and
stromal cells is also under investigation by combining functional
assays, cell-sorting and microarray technologies. We intend to develop
a profile of the genetic networks responsible for the extrinsic
signaling in the stem cell niche.
Stoeckert Lab
Dr. Christian Stoeckert is head of the Computational Biology and Informatics
Laboratory (CBIL) in the Penn Center for Bioinformatics. Research in
the lab has largely been on data integration in the form of a Genomics
Unified Schema (GUS) database system. Major components of GUS are DoTS
(Database of Transcribed Sequences), RAD (RNA Abundance Database), and
TESS (Transcription Element Search Software). Our goal in building this
system has been to discover new genes, understand how groups of genes
are regulated in specific tissue, cell, or conditions, and to place
these genes into the context of regulatory networks. Systems under
study include the human and mouse transcriptome (http://www.allgenes.org),
pancreas development (http://www.cbil.upenn.edu/EPConDB),
hematopoietic stem cells (http://www.cbil.upenn.edu/SCGAP)
and Plasmodium falciparum (http://plasmodb.org).
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