Laurie A. Milner, M.D.

See information for Patients. Viewing information for Researchers.

Dr. Milner's research interests are:

1) Stem Cells

2) Hematopoiesis

3) Transplantation

4) The role of Notch signaling during hematopoietic differentiation of embryonic stem cells.

Research in her laboratory is guided by two fundamental questions: what are the molecular mechanisms responsible for the generation of diverse cell types from pluripotent stem cells, and how do aberrations in normal developmental pathways contribute to pediatric malignancies?

As a model system, they are using embryonic stem (ES) cells to evaluate the role of Notch signaling in hematopoietic cell fate decisions. Signaling through the Notch pathway is critical for appropriate cell fate specification during a variety of developmental processes. The unique capacity of Notch to function both as a cell-surface receptor and transcriptional regulator provides a mechanism by which cell-cell interactions can directly influence gene expression in neighboring cells. This direct communication between cells has two important effects: promoting the self-renewal of uncommitted progenitors and directing equipotent progenitors in the same microenvironmental context to adopt distinct cell fates.

Mammalian hematopoiesis is a unique developmental process in which stem cells continue to generate vast numbers of diverse cell types throughout adult life. As in other systems, Notch appears to influence cell fate decisions at multiple steps during hematopoiesis, having effects that are determined by the presence of specific inductive signals and the precise maturational state of the cell. Defining the role of Notch signaling during hematopoiesis is complicated both by the number of Notch receptors and DSL ligands expressed by hematopoietic and stromal cells, and by the interactions of Notch with other signaling pathways within the intricate hematopoietic regulatory network.

Using a gene targeting strategy to conditionally express the different Notch receptors and DSL ligands at defined stages of in vitro ES cell differentiation and in vivo hematopoiesis, they hope to delineate the effects of Notch signaling on lineage specification and self-renewal of progenitors at various stages of hematopoietic commitment. Their previous studies, as well as those of other investigators, suggest that, in the appropriate context, Notch signaling delays differentiation and promotes expansion of hematopoietic stem/progenitor cells.

Therefore, one of their immediate goals is to use Notch signaling to generate large numbers of hematopoietic stem cells from ES cells; these ES cell-dervived HSCs could provide a versatile alternative stem cell source for transplantation. Given the pervasive role of Notch during development, it's not surprising that aberrations in Notch signaling have been associated with a number of malignancies, including leukemias and lymphomas.

Thus, Dr. Milner hopes that their work will also provide insights as to how alterations in Notch signaling may contribute to pediatric malignancies, many of which represent normal developmental processes gone awry.

Specialty

Hematology / Oncology

Current Appointments

• Associate Professor - Department of Pediatrics (SMD)
• Associate Professor - Department of Pathology and Laboratory Medicine (SMD)
• Associate Professor - Cancer Center (SMD)

Education
MD Pediatrics	University of Texas - Southwestern Medical School	1986
BS Microbiology	University of Montana	1978

Post-Doctoral Training & Residency
Pediatric Hematology/Oncology Fellowship, University of Washington/ Children's Hospital & Medical Center and The Fred Hutchinson Cancer Research Center, Seattle, WA	1990 - 1994
Research Fellow, Virginia Mason Research Center, Seattle, WA	1989 - 1990
Assistant Chief Resident in Pediatrics, University of Washington Affiliated Hospitals/Children's Hospital and Medical Center, Seattle, WA	1989
Residency in Pediatrics, University of Washington Affiliated Hospitals/ Children's Hospital and Medical Center, Seattle, WA	1986 - 1989

Fellowship Awards
Leukemia Society of America Fellowship; Annual Award: $27,000	1993 - 1996
NIH Training Grant	1991 - 1993
American Cancer Society Clinical Fellowship	1990 - 1991

Board Certifications
American Board of Pediatrics, Pediatric Hematology/Oncology	1994 - Present
American Board of Pediatrics	1989 - 2004

Recent Journal Articles
Showing the 5 most recent journal articles. (20 available)
Weber JM; Forsythe SR; Christianson CA; Frisch BJ; Gigliotti BJ; Jordan CT; Milner LA; Guzman ML; Calvi LM. "Parathyroid hormone stimulates expression of the Notch ligand Jagged1 in osteoblastic cells." Bone. 2006; 39(3):485-93. Epub 2006 May 02.
Milner LA. "Revascularization and hematopoeitic recovery following myelosuppression as "Tied" together." Blood (Invited commentary) 106 (2005): 391-392.
Milner LA. "Notch signaling: a key to the pathogeneis of mutiple myeloma?". Blood (Invited commentary) 103 (2004): 3253-3254.
Calvi LM; Adams GB; Weibrecht KW; Weber JM; Olson DP; Knight MC; Martin RP; Schipani E; Divieti P; Bringhurst FR; Milner LA; Kronenberg HM; Scadden DT. "Osteoblastic cells regulate the haematopoietic stem cell niche." Nature. 2003; 425(6960):841-6.
Woolfrey AE; Anasetti C; Storer B; Doney K; Milner LA; Sievers EL; Carpenter P; Martin P; Petersdorf E; Appelbaum FR; Hansen JA; Sanders JE. "Factors associated with outcome after unrelated marrow transplantation for treatment of acute lymphoblastic leukemia in children." Blood. 2002; 99(6):2002-8.