Adam N. Goldfarb, M.D.

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Adam N. Goldfarb, M.D.

Adam N. Goldfarb, M.D. Faculty Profile

GoldfarbAdam

Adam N. Goldfarb, M.D.

Professor of Pathology

Associate Director of Clinical Hematology Laboratory


EDUCATION:

Medical School: Tufts University School of Medicine, MD, 1986

Residency: Anatomic and Clinical Pathology, University of Minnesota Hospital, 1986-1993
Fellowship: Hematopathology, University of Minnesotal Hospital, 1988-1989


CLINICAL:

Hematopathology, including morphologic and immunophenotypic classification of bone marrow and lymph node disorders.

RESEARCH:

Understanding the molecular basis of hematopoiesis and leukemogenesis. The laboratory is focused on two specific issues relevant to these topics: 1) structural and functional characterization of the SCL/tal transcription factor, which plays key roles in normal stem cell development and in human leukemia development; and 2) unraveling signaling pathways that direct multipotent progenitor cells toward megakaryocyte development.

SCL/tal participates in a large multiprotein complex--a hematopoietic transcriptosome--which programs, through target gene regulation, the development of hematopoietic tissue during embryogenesis. This same multiprotein complex also contributes to disease, becoming inappropriately expressed in thymocytes in most cases of T cell acute lymphoblastic leukemia. Current research projects in the lab aim at defining relevant components of this transcriptional complex and at understanding the structural basis for the physical interaction of SCL/tal with other components of the complex. Techniques include site-directed mutagenesis, protein expression in yeast and in mammalian cells, in vivo and in vitro protein interaction assays, immunofluorescence microscopy, immunoprecipitation, assays for DNA binding by protein, promoter assays, and computational molecular modeling.

Platelet producing cells, megakaryocytes, arise from a bipotential progenitor cell, the BFU-E/Meg which can give rise to erythroid cells (red blood cells) or to megakaryocytes. The signals which determine the pathway chosen--erythroid versus megakaryocytic-- remain uncharacterized. The laboratory is currently developing a series of mutant cell lines selected for specific defects in megakaryocytic differentiation. An array of molecular and cell biologic techniques will be employed to define at the molecular level the defects in these mutants and thereby gain some understanding of the key molecular players in megakaryocytic signaling pathways.

REFERENCES:

  • Choi, Y., Elagib, K. E., Delehanty, L. L., Goldfarb, A. N. : Erythroid inhibition by the leukemic fusion AML1-ETO is associated with impaired acetylation of the major erythroid transcription factor GATA-1.  Cancer Res., In Press, 2006.
  • Elagib, K. E., Xiao, M., Hussaini, I. M., Delehanty, L. L., Palmer, L. A., Racke, F. K., Birrer, M. J., Shanmugasundaram, G., McDevitt, M. A., Goldfarb, A. N.: Jun blockade of erythropoiesis: a role for repression of GATA-1 by HERP2. Mol. Cell. Biol., 24:7779-7794, 2004.
  • Elagib, K.E., Racke, F.K., Mogass, M., Khetawat, R., Delehanty, L.L., Goldfarb, A.N.: RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation. Blood, 101:4333-4341, 2003.
  • Delehanty, L.L., Mogass, M., Gonias, S.L., Racke, F.K., Johnstone, B., Goldfarb, A.N.: Stromal inhibition of megakaryocytic differentiation is associated with blockade of sustained Rap1 activation.   Blood, 101:1744-1751, 2003.
  • Goldfarb, A.N., Delehanty, L.L., Wang, D., Racke, F.K., Hussaini, I.M.: Stromal inhibition of megakaryocytic differentiation correlates with blockade of signaling by PKC-e and ERK/MAPK. J. Biol. Chem., 276:29526-29530, 2001.
  • Goldfarb, A.N., Wang, D., Racke, F.K.: Induction of megakaryocytic differentiation in primary human erythroblasts: a physiologic basis for leukemic lineage plasticity. Am. J. Pathol., 158(4):1191-1198, 2001.
  • Racke, F.K., Wang, D., Zaidi, Z, Kelley, J., Visvader, J., Soh, J-W., Goldfarb, A.N.: A potential role for protein kinase C-e in regulating megakaryocytic lineage commitment.  J. Biol. Chem., 276:522-528, 2001.

A current list of Dr. Goldfarb's publications can be found at PubMed