Professor, Stem Cell Biology
Dr. rer. nat., Universität Köln
Postdoctoral training:
Stanford University
Eli Lilly Research Laboratory, La Jolla
Research Interests:
Stem Cell Biology, Regenerative Medicine.
Dr. Muller-Sieburg’s research is focused on understanding the cellular and molecular mechanisms that regulate hematopoietic stem cells (HSC). The defining features of all stem cells are self-renewal and differentiation capacity. These features make HSC ideally suited for replacement therapy. HSC are an important model for tissue specification and regeneration. The Muller-Sieburg group found that adult HSC are heterogeneous in self-renewal and differentiation capacity. Mathematical modeling revealed a limited number of different types of HSC. Differences in these types of HSC are epigenetically fixed, and this fixation is acquired early in embryonic development. They also demonstrated that ageing leads to a reduction of HSC types. The aged HSC compartment has lost rapidly repopulating lymphoid-biased HSC and is dominated by slow myeloid-biased HSC. Both genetic mechanisms and epigenetic modifications contribute to the regulation of stem cell behavior. How these epigenetic and genetic programs are established during development and how they are altered in aging are questions addressed by that group. Another interest of the Muller-Sieburg group is to define why certain types of normal stem cells can transform into leukemic cancer stem cells. They are using computer simulation and mathematical approaches to predict which genes and which modifications will make a stem cell susceptible to become a leukemic stem cell.
Representative Publications:
1. Muller-Sieburg CE, Whitlock CA, Weissman IL. 1986. Isolation of two early lymphocyte progenitors from mouse marrow: a committed pre-pre B cell and a clonogenic Thy-1lo hematopoietic stem cell. Cell, 44:653.
2. Muller-Sieburg CE. 1991. Separation of pluripotent stem cells and early B lymphocyte precursors with antibody Fall-3. J Exp Med, 174 : 161.
3. Wineman JP, Moore K, Lemischka IA, Muller-Sieburg CE. 1996. Functional heterogeneity of the hematopoietic microenvironment: Rare stromal elements maintain long-term repopulating stem cells. Blood 87:4082-4090
4. Muller-Sieburg CE, Cho RH, Karlsson L, Huang J-F, Sieburg HB. 2004. Myeloid-Biased Hematopoietic Stem Cells have Extensive Self-Renewal Capacity but Generate Diminished Lymphoid Progeny with Impaired IL-7 Responsiveness. Blood, 103: 4111-8
5. Cho RH, Sieburg HB, Muller-Sieburg CE. 2008. A New Mechanism For The Aging of Hematopoietic Stem Cells: Aging Changes the Clonal Composition of The Stem Cell Compartment but Not Individual Stem Cells. Blood, 111: 5553-5561
Biography:
Dr. Muller-Sieburg is a Professor at the Sidney Kimmel Cancer Center. Before Joining SKCC she was an Associate Professor at the Medical Biology Institute in La Jolla. Dr Muller-Sieburg graduated from the Institute of Genetics at the University of Cologne. Her graduate work with Klaus Rajewsky focused on the regulation of the immune response by anti-idiotope antibodies. She worked with Irv Weissman at Stanford as postdoctoral fellow. During that time she developed the first antigenic profile of hematopoietic stem cells and demonstrated that stem cells can be enriched as Lin-Thy-1lo cells. This laid the foundation for stem cell work in the Weissman lab. Dr. Muller-Sieburg joined the Eli Lilly research lab in La Jolla where she continued to develop new cell surface markers for HSC. She also developed a system where mesenchymal stem cells/ stromal cells are used to support HSC ex vivo. She pursued these studies as NIH funded projects when she joined the Medical Biology as Assistant Professor. At that time, she became a Leukemia Society Scholar and in 1992 won the Stohlman Memorial Scholar Award. She was the first to identify and map genes that control the frequency of HSC. In 1998 she joined the Sidney Kimmel Cancer Center as a Professor, where she started programs in HSC ageing and epigenetics. Her program has been funded by NIH, the American Cancer Society, the Leukemia Society, and DOD.
