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Adam N. Goldfarb

Adam N. Goldfarb

Professor, Pathology

Primary Location
PO Box 800904
3232 MR-5
Primary Phone Number
982.059.3
Email
[email protected]

Bio & Overview

The lab has two related areas of interest: 1) development of red cells and platelets within bone marrow precursors, and 2) the effects of iron deprivation on red cell and platelet development. The platelet producing cells in the bone marrow, megakaryocytes, develop from a precursor cell that also gives rise to red blood cells. The genetic programming events that dictate the development of megakaryocytes along a pathway different from the red blood cells remain poorly understood. Nevertheless, these programming events are clearly disrupted in some types of human leukemia and in several human disorders of platelet production. Previous work in our lab has identified two proteins, RUNX1 and GATA-1, as key players in programming megakaryocyte development. These two proteins communicate with one another in this process using a novel signaling mechanism involving an enzyme known as Cdk9. Future experiments will provide a detailed understanding of how RUNX1, GATA-1, and Cdk9 cooperate in programming megakaryocyte development in mice and in human marrow cells. Importantly, several drugs currently in human trials are known to affect Cdk9 function and could profoundly influence megakaryocyte development. Iron deficiency represents a frequent cause of anemia and causes the bone marrow to decrease production of red blood cells. In addition to iron deficiency anemia, anemias associated with cancer, kidney disease, chronic inflammation, and aging also are associated with impaired red cell production by the bone marrow. These latter anemias arise in part because of inadequate transport of iron from storage cells to the red cell precursors in the marrow. In particular, red cell precursors sense an iron deficiency even though total body iron stores are frequently increased.This project has identified the mechanisms by which bone marrow cells sense iron availability and adjust red cell production accordingly. Preliminary studies have led to compounds which can either reverse or mimic the response of marrow cells to diminished iron availability. These studies therefore offer novel approaches for the treatment of several types of chronic anemia and for the treatment of diseases associated with excessive red cell production such as polycythemia.

Academic Information

Department
Pathology
Academic Title
Professor

Primary Education

  • BA, English, Brown University, 1982
  • MD, Medicine, Tufts University, Boston, MA, 1986

Other Appointments

  • Pharmacology
  • Professor, MOMD

Other Affiliations

  • Member, Immunology/Immunotherapy Program
  • MSTP
  • Professor, BIMS

Research Interests

Hematopathology and Understanding the Molecular Basis of Hematopoiesis and Leukemogenesis

Research Disciplines

  • Biochemistry
  • Cancer Biology
  • Epigenetics
  • Experimental Pathology
  • Metabolism
  • Molecular Biology
  • Translational Science

Research Opportunities

  • Biochemistry
  • Cancer Biology
  • Cellular and Molecular Metabolism
  • Epigenetics
  • Experimental Pathology
  • Molecular Biology

PhD Programs

  • Experimental Pathology

Selected Publications

2022

Elagib, K. E., Brock, A., Clementelli, C. M., Mosoyan, G., Delehanty, L. L., Sahu, R. K., . . . Goldfarb, A. N. (2022). Relieving DYRK1A repression of MKL1 confers an adult- like phenotype to human infantile megakaryocytes. JOURNAL OF CLINICAL INVESTIGATION, 132(19). doi:10.1172/JCI154839

White, Z. I. I. I., Gru, A. A., & Goldfarb, A. N. (2022). Liver kinase B1 (LKB1) in murine erythroid progenitors modulates erythropoietin setpoint in association with maturation control. BLOOD CELLS MOLECULES AND DISEASES, 97. doi:10.1016/j.bcmd.2022.102688

2021

Goldfarb, A. N., Freeman, K. C., Sahu, R. K., Elagib, K. E., Holy, M., Arneja, A., . . . Delehanty, L. L. (2021). Iron control of erythroid microtubule cytoskeleton as a potential target in treatment of iron-restricted anemia. NATURE COMMUNICATIONS, 12(1). doi:10.1038/s41467-021-21938-2

2019

Balogh, P., Adelman, E. R., Pluvinage, J. V., Capaldo, B. J., Freeman, K. C., Singh, S., . . . Goldfarb, A. N. (2020). RUNX3 levels in human hematopoietic progenitors are regulated by aging and dictate erythroid-myeloid balance. HAEMATOLOGICA, 105(4), 905-913. doi:10.3324/haematol.2018.208918

2018

Elagib, K. E., Brock, A. T., & Goldfarb, A. N. (2018). Megakaryocyte ontogeny: Clinical and molecular significance. EXPERIMENTAL HEMATOLOGY, 61, 1-9. doi:10.1016/j.exphem.2018.02.003

2017

Elagib, K. E., Lu, C. -H., Mosoyan, G., Khalil, S., Zasadzinska, E., Foltz, D. R., . . . Goldfarb, A. N. (2017). Neonatal expression of RNA-binding protein IGF2BP3 regulates the human fetal-adult megakaryocyte transition. JOURNAL OF CLINICAL INVESTIGATION, 127(6), 2365-2377. doi:10.1172/JCI88936

2014

Elagib, K. E., & Goldfarb, A. N. (2014). Megakaryocytic irreversible P-TEFb activation. CELL CYCLE, 13(12), 1827-1828. doi:10.4161/cc.29324

2013

Elagib, K. E., Rubinstein, J. D., Delehanty, L. L., Ngoh, V. S., Greer, P. A., Li, S., . . . Goldfarb, A. N. (2013). Calpain 2 Activation of P-TEFb Drives Megakaryocyte Morphogenesis and Is Disrupted by Leukemogenic GATA1 Mutation. DEVELOPMENTAL CELL, 27(6), 607-620. doi:10.1016/j.devcel.2013.11.013

Richardson, C. L., Delehanty, L. L., Bullock, G. C., Rival, C. M., Tung, K. S., Kimpel, D. L., . . . Goldfarb, A. N. (2013). Isocitrate ameliorates anemia by suppressing the erythroid iron restriction response. JOURNAL OF CLINICAL INVESTIGATION, 123(8), 3614-3623. doi:10.1172/JCI68487

2012

Delehanty, L. L., Bullock, G. C., & Goldfarb, A. N. (2012). Protein kinase D-HDAC5 signaling regulates erythropoiesis and contributes to erythropoietin cross-talk with GATA1. BLOOD, 120(20), 4219-4228. doi:10.1182/blood-2011-10-387050

Rubinstein, J. D., Elagib, K. E., & Goldfarb, A. N. (2012). Cyclic AMP Signaling Inhibits Megakaryocytic Differentiation by Targeting Transcription Factor 3 (E2A) Cyclin-dependent Kinase Inhibitor 1A (CDKN1A) Transcriptional Axis. JOURNAL OF BIOLOGICAL CHEMISTRY, 287(23), 19207-19215. doi:10.1074/jbc.M112.366476

2011

Talbot, A. -L., Bullock, G. C., Delehanty, L. L., Sattler, M., Zhao, Z. J., & Goldfarb, A. N. (2011). Aconitase Regulation of Erythropoiesis Correlates with a Novel Licensing Function in Erythropoietin-Induced ERK Signaling. PLOS ONE, 6(8). doi:10.1371/journal.pone.0023850

2010

Goldfarb, A. N. (2010). Coordinating red cell differentiation with cell cycle arrest: GATA-1 activation of p21 Comment on: Papetti M, et al. Cell Cycle 2010; 9: 1972-80. CELL CYCLE, 9(11), 2061. Retrieved from https://www.webofscience.com/

Bullock, G. C., Delehanty, L. L., Talbot, A. -L., Gonias, S. L., Tong, W. -H., Rouault, T. A., . . . Goldfarb, A. N. (2010). Iron control of erythroid development by a novel aconitase-associated regulatory pathway. BLOOD, 116(1), 97-108. doi:10.1182/blood-2009-10-251496