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Diane Krause, MD, PhD
Professor of Laboratory Medicine and Cell Biology
Associate Director, Yale Stem Cell Center
Associate Director, Transfusion
Medicine Service
Director, Frisbee
Laboratory for Hematopoietic Graft Engineering
Director, Yale Center of Excellence in Molecular Hematology
Krause
Laboratory
Amistad 237
203-737-1678
diane.krause@yale.edu
Undergraduate:
ScB, 1982, Brown University
MD: 1990, University of Pennsylvania
PhD: 1990, University of Pennsylvania
Clinical Pathology Residency: University of Pennsylvania
Research Fellowship: Johns Hopkins Oncology Center
Community
of Science Biosketch
Research Interests
The overall goals of my research are to characterize hematopoietic
stem and progenitor cells, and to define the molecular mechanisms
that regulate the self-renewal and differentiation of these cells.
These findings may then be used in the development of improved strategies
for bone marrow/stem cell transplantation as well as for developing
novel strategies for treating leukemia and lymphoma. CD34, a cell-surface
glycophosphoprotein, is expressed in the hematopoietic system exclusively
on stem and progenitor cells, and represents the only such molecule
yet identified.
Specifically,
my laboratory is pursuing three projects. The first is focused
on defining the molecular mechanism(s) that regulate gene expression
during developmental hematopoiesis. Using molecular biological techniques,
I am identifying promoter and silencer regions upstream of the CD34
gene, and defining the protein factors that regulate CD34
expression via interaction with these critical regions. In addition,
we are using PCR subtraction techniques and cDNA arrays to identify
additional genes that are expressed exclusively on hematopoietic
stem cells. The second focus in my laboratory is the development
and use of murine bone marrow transplantation models for a.) selection
of stem cells, b.) purging of unwanted cells (in the autologous
setting), c.) gene therapy, and d.) as a predictive model for human
cell engraftment in clinical transplantation. Projects include using
limiting numbers of CD34+
and CD34- bone
marrow cells to engraft lethally irradiated mice, and characterizing
gene expression in the confirmed stem cell populations by RT-PCR,
Northern analysis, screening arrays and FACS analysis. Also, related
to this focus are studies in which we use human stem cells to engraft
in highly immunodeficient mice to determine the functional capacity
of the human cells. The third focus in the lab is the identification
of cells in the bone marrow that are capable of differentiating
into nonhematopoietic tissues including chondrocytes, osteoblasts,
myocytes, pneumocytes and hepatocytes.
References
- Krause
DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R,
Neutzel S, Sharkis SJ. Multi-organ, multi-lineage engraftment
by a single bone marrow-derived stem cell. Cell 105:369-377, 2001.
- Perez
L, Rinder HM, Wang C, Tracey JB, Maun N, Krause DS. Xenotransplantation
of immunodeficient mice with human CD34+
cells provides an in-vivo model for munam megakaryocytopoiesis
and platelet production . Blood 97:1635-43, 2001.
- Taranenko
N, Krause DS. Regulation of CD34
transcription by Sp1 requires sites upstream and downstream of
the transcription start site. Experimental Hematology, 28: 974-984,
2000.
- Theise
ND, Nimmakayalu M, Gardner R, Illei PB, Morgan G, Teperman L,
Henegariu O, Krause DS. Liver from bone marrow in humans. Hepatology,
32: 11-16, 2000.
- Theise
ND, Badve S, Saxena R, Henegariu O, Sell S, Crawford JM, Krause
DS. Derivation of hepatocytes from bone marrow cells in mice after
radiation-induced myeloablation. Hepatology, 31: 235-240, 2000.
For
more information, please visit the Krause
Laboratory. |