Adam N. Goldfarb, M.D.
Professor of Pathology
Chief, Division of Experimental Pathology
Associate Director of Clinical Hematology Laboratory
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
Hematopathology, including morphologic and immunophenotypic classification of bone marrow and lymph node disorders.
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.
Elagib KE, Goldfarb AN: Megakaryocytic irreversible P-TEFb activation. Cell Cycle 2014, 13:1827-1828.http://www.ncbi.nlm.nih.gov/pubmed/24866976. DOI: 10.4161/cc.29324.
Richardson CL, Delehanty LL, Bullock GC, Rival CM, Tung KS, Kimpel DL, Gardenghi S, Rivella S, Goldfarb AN: Isocitrate ameliorates anemia by suppressing the erythroid iron restriction response. J Clin Invest 2013, 123:3614-3623. http://www.ncbi.nlm.nih.gov/pubmed/23863711. DOI: 10.1172/JCI68487.
Elagib KE, Rubinstein JD, Delehanty LL, Ngoh VS, Greer PA, Li S, Lee JK, Li Z, Orkin SH, Mihaylov IS, Goldfarb AN: Calpain 2 activation of P-TEFb drives megakaryocyte morphogenesis and is disrupted by leukemogenic GATA1 mutation. Dev Cell 2013, 27:607-620. http://www.ncbi.nlm.nih.gov/pubmed/24369834. DOI: 10.1016/j.devcel.2013.11.013.
Delehanty LL, Bullock GC, Goldfarb AN: Protein kinase D-HDAC5 signaling regulates erythropoiesis and contributes to erythropoietin cross-talk with GATA1. Blood 2012, 120:4219-4228.http://www.ncbi.nlm.nih.gov/pubmed/22983445. DOI: 10.1182/blood-2011-10-387050.
Rubinstein JD, Elagib KE, Goldfarb AN: Cyclic AMP signaling inhibits megakaryocytic differentiation by targeting transcription factor 3 (E2A) cyclin-dependent kinase inhibitor 1A (CDKN1A) transcriptional axis. J Biol Chem 2012, 287:19207-19215. http://www.ncbi.nlm.nih.gov/pubmed/22514271. DOI: 10.1074/jbc.M112.366476.
Talbot AL, Bullock GC, Delehanty LL, Sattler M, Zhao ZJ, Goldfarb AN: Aconitase regulation of erythropoiesis correlates with a novel licensing function in erythropoietin-induced ERK signaling. PLoS One 2011, 6:e23850.http://www.ncbi.nlm.nih.gov/pubmed/21887333. DOI: 10.1371/journal.pone.0023850.
Bullock GC, Delehanty LL, Talbot AL, Gonias SL, Tong WH, Rouault TA, Dewar B, Macdonald JM, Chruma JJ,Goldfarb AN: Iron control of erythroid development by a novel aconitase-associated regulatory pathway. Blood 2010, 116:97-108. http://www.ncbi.nlm.nih.gov/pubmed/20407036. DOI: 10.1182/blood-2009-10-251496.
Goldfarb AN: Coordinating red cell differentiation with cell cycle arrest: GATA-1 activation of p21. Cell Cycle 2010, 9:2061. http://www.ncbi.nlm.nih.gov/pubmed/20559028.
Goldfarb AN: Megakaryocytic programming by a transcriptional regulatory loop: A circle connecting RUNX1, GATA-1, and P-TEFb. J Cell Biochem 2009, 107:377-382. http://www.ncbi.nlm.nih.gov/pubmed/19350569. DOI: 10.1002/jcb.22142.
Yeh JR, Munson KM, Elagib KE, Goldfarb AN, Sweetser DA, Peterson RT: Discovering chemical modifiers of oncogene-regulated hematopoietic differentiation. Nat Chem Biol 2009, 5:236-243.http://www.ncbi.nlm.nih.gov/pubmed/19172146. DOI: 10.1038/nchembio.147.
Elagib KE, Mihaylov IS, Delehanty LL, Bullock GC, Ouma KD, Caronia JF, Gonias SL, Goldfarb AN: Cross-talk of GATA-1 and P-TEFb in megakaryocyte differentiation. Blood 2008, 112:4884-4894.http://www.ncbi.nlm.nih.gov/pubmed/18780834. DOI: 10.1182/blood-2008-03-145722.
A current list of Dr. Goldfarb’s publications can be found at PubMed