Diane  Krause, M.D., Ph.D.

Training:

Sc.B., Honors, Biology, Brown University , 1982
M.D., University of Pennsylvania, Cell Biology, 1990
Ph.D., University of Pennsylvania, Cell and Molecular Biology, 1990
Residency, Clinical Pathology, University of Pennsylvania, 1990-1993
Fellowship, Johns Hopkins Oncology Center, 1992-1995
Chief Resident, Clinical Pathology, University of Pennsylvania, 1992

Expertise:

Hematopoiesis, Stem cell Biology, Blood Banking

Research Interests:

The major focus of work in my laboratory is on the identification and regulation of stem cells. Projects are available that focus on 1.) molecular mechanisms that regulate early hematopoiesis, 2.) murine and xenogeneic transplantation models to study stem cell function, and 3.) bone marrow transplantation to identify stem cells in the bone marrow, and to identify their "transdifferentiation" ability. Each of these projects requires multiple cellular and molecular laboratory techniques, and the development of vectors to obtain tissue-specific transgene expression. The projects are outlined below.

1.) Stem cell regulation
The overall goals of this work are to characterize hematopoietic stem and progenitor cells, and to define the molecular mechanisms that regulate the self-renewal and differentiation of these cells. The first project is focused on studying genes expressed early in developmental hematopoiesis. Using molecular biological techniques, you will identify promoter and silencer regions upstream of multiple genes that are uniquely expressed on hematopoietic stem cells, and define the transcription factors that regulate gene expression via interaction with these critical regions. In addition, using PCR subtraction techniques and cDNA arrays, you will identify additional genes that are expressed exclusively on hematopoietic stem cells.

2.) Bone Marrow Transplantation and Stem Cell Biology
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 recipient 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 xenogeneic transplant studies in which you will transplant human stem cells into highly immunodeficient mice to determine the functional capacity of the human cells.

3.) Transdifferentiation of bone marrow cells into nonhematopoietic tissues
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. Gene therapy vectors (viral and nonviral) will be used to obtain liver-specific and lung-specific transgene expression. The clinical applications of this work include treatment of enzyme deficiencies the liver and lung such as Gaucher's disease and cystic fibrosis.

Professional Service:

American Medical Women's Association
Physicians for Social Responsibility (President, Philadelphia Chapter, 1990-1992)
American Society of Clinical Pathologists
International Society for Hematotherapy and Graft Engineering
American Association of Blood Banks
International Society of Experimental Hematology
American Society of Hematology

Selected Publications: