Stem Cells, Differentiation and Cancer

Program Leader: Ulrich Steidl, M.D., Ph.D.
Co-Program Leader: Amit Verma, M.B.B.S.

Stem Cells, Differentiation and Cancer is a newly configured Cancer Center program that has brought together investigators working on B-cell leukemia/lymphomas with investigators that study myeloid malignancies along with recently recruited researchers focused on cancer stem cells. While there has been an increasing focus on translation in the hematological malignancies, this program continues to remain an important resource of basic science discovery on mechanisms of transcription (including histone and chromatin biology), lineage determination and differentiation, splicing and translation at the biochemical and molecular levels. Research extends to precursors of neural, hepatic, and mammary origin and their differentiation.

There have been important discoveries regarding the pathogenesis of myelodysplasia, signal-transduction strategies to stimulate hematopoiesis and delay transformation into acute leukemia. High resolution genomic studies using assays developed at Einstein have characterized the methylome in leukemia, myelodysplasia, myeloproliferative neoplasms, and lymphomas, revealing novel prognostic and pathogenic insights. Quantitative and qualitative alterations in stem and progenitor cells were identified in myelodysplastic syndromes and leukemia implicating primitive specific cells in disease-relapse.

The discovery of Skp2 as a critical proliferative signal in pituitary tumors, in which retinoblastoma protein has been inactivated, has identified it as a novel therapeutic target with potential relevance to other malignancies such as prostate cancer. Finally, groundbreaking studies have revealed the role of the sympathetic nervous system in the regulation of the hematopoietic stem cell niche with the potential to pharmacologically augment the circadian mobilization of hematopoietic stem cells from the bone marrow.

These studies are also linked to the role of the sympathetic nervous system in the migration of monocyte/macrophages and the role of macrophages in the bone marrow stem cell niche as a determinant of breast and other cancer metastasis. Many of these basic studies have been translated into correlative and clinical therapeutic trials at AECC and have identified novel targets for drug development pursued by investigators in the Experimental Therapeutics Program.