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Merav Socolovsky, Ph.D.,MBBSAcademic Role: Assistant Professor
Faculty Appointment(s) In:
Other Affiliation(s):
Molecular mechanisms regulating the homeostasis of hematopoietic progenitros
A major obstacle to molecular study of red-cell progenitors had been the lack of direct means with which to identify these cells within the blood forming tissue. We have recently developed novel methodology that overcomes this difficulty. Using cell-surface markers, we are able to identify red cell progenitors at specific maturation stages directly within tissue (Figure 2). We are employing this novel methodology in combination with other molecular and genetic tools in the mouse, to identify rate-determining steps and new stress-responsive genes in red cell progenitors. Genes identified by this work may shed light on mechanisms of leukemic transformation and red cell production disorders. They may offer ways to increase the efficiency of stem cell- based therapies, in conditions such as anemias, recovery from chemotherapy or bone -marrow transplantation.
Selected PublicationsSocolovsky, M., Dusanter-Fourt, I., Lodish, H.F. The prolactin receptor and severly truncated erythropoietin receptors support differentiation of erythroid progenitors. J Biol. Chem. (Communication), 1997; 272:14009-14012. Socolovsky, M.,Fallon, A.E.J., Lodish, H.F. The prolactin receptor rescues EpoR -/- erythroid progenitors and replaces EpoR in a synergistic interaction with c-kit. Blood, (Rapid Communication), 1998; 92(5):1491-1496. Socolovsky, M., Fallon, A.E.J., Wang, S., Brugnara, C., Lodish, H.F. Fetal anemia and apoptosis of red-cell progenitors in Stat5a-/-Stat5b-/- mice: a direct role for Stat5 in Bcl-xL - induction. Cell, 1999; 98:181-191. Brisken, C.*, Socolovsky, M.*, Lodish, H.F., Weinberg. R.A. The Signaling Domain of the Erythropoietin Receptor Rescues Prolactin Receptor-Mutant Mammary Epithelium. PNAS, 2002; 99:14241-14245*contributed equally to this work Zhang. J., Socolovsky, M. Gross. A., Lodish., H.F. Role of Ras signaling in erythroid differentiation of fetal liver cells: functional analysis by a flow-cytometry- based novel culture system. Blood, 2003; 102:3938-3946. Liu, Y., Pop, R., Sadegh, C., Brugnara, C., Haase, V.H., Socolovsky, M. Suppression of Fas-FasL co-expression by erythropoietin mediates erythroblast expansion during the erythropoietic stress-response in vivo.Blood, 2006; 108:123-133 Socolovsky, M. Molecular Insights into Erythropoietic Stress. Current Opinion in Hematology, in press. Socolovsky, M.,Murrell, M., Liu, Y., Pop, R., Porpiglia, E., and Levchenko, A. Negative Autoregulation by Fas Mediates Robust Fetal Erytrhopoiesis . PLoS Biology, 2007; 5(10): e252.doi:10 Rotation projects includeIdentification of candidate cell-cycle and apoptosis genes, as well as novel genes, expressed differentially in red-cell progenitors, in tissue derived from mouse-models of increased erythropoietic rate. These projects will include a combination of cell culture, flow-cytometry and 'gene chip' microarray analysis. BiographyMerav Socolovsky received her BA degree (1983) from the University of Cambridge, UK, and her MBBS degree (equivalent to MD in the USA) from University College, London, U.K. (1986). She became Member of the Royal College of Physicians (1989) and received a Medical Research Council (U.K.) Training Fellowship to study for her Ph.D. degree at the Physiological Laboratory, University of Cambridge, U.K. (1994). She received a Howard Hughes Training Fellowship for Physicians (1994) to pursue postgraduate work in the laboratory of Harvey Lodish at the Whitehead Institute, Cambridge MA. She joined the faculty of the Department of Pediatrics and Department of Cancer Biology at the University of Massachuesettes Medical School in 2004. She is the recipient of a National Cancer Institute Howard Temin (KO1) Career Development Award (2002), a Charles Hood Foundation Child Health Research Award (2004), an award from the Robert Leet and Clara Guthrie Patterson Trust (2005), and an American Cancer Society Scholar grant (2006).
Office: LRB 403
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The production of differentiated blood cells requires tight coordination of three processes: cell division, cell survival, and expression of lineage-specific genes (maturation). Coordination of these three processes is critical for the production of exactly the right number of blood cell progeny per unit time (blood cell production rate). Conversely, lack of coordination between cell division, cell survival and cell maturation is characteristic of leukemic cells. Our lab is focusing on understanding how cell-cycle progression, cell survival and cell maturation are coordinated within red-cell progenitors. We are using mouse models in which the rate of red cell formation is vastly increased over the normal rate, in order to elucidate the molecular mechanisms that control progenitor cell homeostasis.
55 Lake Avenue North Worcester, MA 01605