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
|
