Alan D. D'Andrea, M.D.

Alvan T. and Viola D. Fuller Amer. Cancer Society Prof. of Radiation Oncology

Department of Medicine
Dana-Farber Cancer Institute
44 Binney St., Mayer Building, Room 640
Boston, MA 02115
Tel: 617-632-2080
Fax: 617-632-5757
e-mail:a_dandrea@dfci.harvard.edu
8 research fellows, 2 graduate students

A primary focus of our laboratory is signal transduction by hematopoietic growth factor receptors. We study the erythropoietin receptor and its interaction with the Friend Virus envelope protein, gp55. The erythropoietin receptor (EPO-R), which is a member of the cytokine receptor superfamily, plays a central role in murine erythroleukemia (EL). Several independent murine erythroleukemia cells lines have been isolated and, in each case, there is a constitutive activation of the EPO-R. The EPO-R can be inactivated by coexpression of EPO (autocrine leukemic cell growth), a point mutation in the EPO-R primary sequence, or coexpression of the Friend Spleen Focus-Forming Virus gp55 glycoprotein.

Following activation, the EPO-R (and other cytokine receptors) activates multiple signal transduction pathways leading to cell proliferation and cell growth. For instance, the EPO-R activates the JAK/STAT signaling pathway and the Ras/Raf/MAPk signaling pathway. More recently, we have identified a family of ubiquitin-specific proteases that regulate cytokine mediated cellular growth. How these ubiquitin-specific proteases modulate signal transduction is a major focus of our efforts.

References:

1. Zhu Y, Carroll M, Papa FR, Hochstrasser M, D’Andrea AD. DUB-1, a deubiquitinating enzyme with growth-suppressing activity. Proc Natl Acad Sci USA 93:3275-3279, 1996.
2. Zhu Y, Lambert K, Corless C, D’Andrea AD. DUB-2 Is a member of a novel family of cytokine-inducible deubiquitinating enzymes. J Biol Chem 272:51-57, 1997.
3. Ney PA, D’Andrea AD. Friend erythroleukemia revisited. Blood 96:3675-3680, 2000.