Professor of Pediatrics
Education and Experience
- Harvard Medical School (Boston MA)/ (1983)
- Children's Hospital (Boston MA)/ Pediatrics (1986)
- The Johns Hopkins Hospital (Baltimore MD)/ Pediatric Hematology/Oncology (1989)
- Pediatric Hematology/Oncology, American Board of Pediatrics (2005)
- Pediatrics, American Board of Pediatrics (1987)
- Pediatric Oncology
- Sidney Kimmel Comprehensive Cancer Center
1983 cum laude, Harvard Medical School
1991-1996 Searle Scholar Award, Chicago Community Trust
1998-2003 Scholar Award, Leukemia and Lymphoma Society
2003 Stohlman Scholar, Leukemia and Lymphoma Society
2004 Oncology Center Director''s Teaching Award in Basic Science, Johns Hopkins University
- Acute Lymphoblastic Leukemia
- Acute Myeloid Leukemia
- Chronic Myeloid Leukemia
- General Pediatrics
- Germ Cell Tumors
- Hodgkin's Disease
- Myelodysplastic Syndrome
- Non-Hodgkin's Lymphoma
- Pediatric Oncology
- Wilms tumor
Lay Summary -
Dr. Friedman investigates mechanisms through which normal proteins control the formation of bone marrow stem cells and how these stem cells then develop into neutrophils and monocytes. He is also studying how normal bone marrow cells become transformed into acute myeloid leukemia (AML). In conducting these studies he focuses on two proteins, RUNX1 and C/EBPa, which regulate normal bone marrow development but are also commonly mutated in AML. Dr. Friedman is attempting to build on his basic research to develop useful clinical applications. In particular, he is pursuing small molecules that interfere with the action of leukemic RUNX1 or C/EBPa proteins as potential novel therapies for AML, and he is investigating means to expand normal blood stem cells to benefit patients with marrow failure or those many patients receiving chemotherapy who would benefit from blood product support to avoid anemia, bleeding, and infections.
Technical Summary -
RUNX1 is a transcription factor required for the formation of the hematopoietic stem cell (HSC) and for its further maturation. RUNX1 is commonly mutated or involved in chromosomal translocations associated with AML or ALL. Dr. Friedman''s laboratory is investigating the mechanisms that allow RUNX1 to regulate normal hematopoietic stem cells and myeloid differentiation and to stimulate cell cycle progression. He ultimately envisions developing means to manipulate RUNX1 to assist formation and expansion of HSC from embryonic stem cells and to assist formation of autologous neutrophils to benefit patients with neutropenia. In addition, Dr. Friedman is investigating how mutations of RUNX1 or its partner CBFb contribute to acute leukemia, focusing on CBFb-SMMHC, a fusion oncoprotein expressed from the inv(16) chromosome in a subset of AML patients. Ultimately, he would like to identify small molecules that target CBFb-SMMHC to assist in the therapy of AML.
C/EBPa is a transcription factor required for formation of normal neutrophils and monocytes. C/EBPa is also commonly mutated in blasts derived from patients with AML. Dr. Friedman''s laboratory is investigating how C/EBPa cooperates with other proteins, including cytokines such as G-CSF or M-CSF, to control normal myeloid development. In addition, he is investigating how mutant forms of C/EBPa contribute to AML, in particular focusing on how interaction between C/EBPa and another transcription factor, NF-kB, inhibits apoptosis. By mapping the amino acids through which these proteins interact, Dr. Friedman hopes to ultimately design small molecules that prevent their interaction to induce leukemic cell death and contribute to the therapy of AML. As C/EBPs and NF-kB are also expressed also in other malignancies and in inflammatory cells which contribute to cancer formation and progression, such a small molecule might in addition have broader utility as a novel therapeutic.
Chintagumpala, M.M.; Friedman, H.S.; Stewart, C.F.; Kepner, J.; McLendon, R.E.; Modrich, P.L.; McCluggage, C.; Burger, P.; Holmes, E.; Thompson, S.; Rutka, J.; Michalski, J.; Woo, S.; Blaney, S.M.; Kun, L.E.; Horowitz, M.E.; Pediatric Oncology Group, S. A phase II window trial of procarbazine and topotecan in children with high-grade glioma: a report from the children's oncology group. Journal of neuro-oncology. 2006 Apr;77(2):193-198.
Nguyen-Khac, F.; Della Valle, V.; Lopez, R.G.; Ravet, E.; Mauchauffe, M.; Friedman, A.D.; Huang, L.E.; Fichelson, S.; Ghysdael, J.; Bernard, O.A. Functional analyses of the TEL-ARNT fusion protein underscores a role for oxygen tension in hematopoietic cellular differentiation. Oncogene. 2006 Aug 10;25(35):4840-4847.
Suh, H.C.; Gooya, J.; Renn, K.; Friedman, A.D.; Johnson, P.F.; Keller, J.R. C/EBPalpha determines hematopoietic cell fate in multipotential progenitor cells by inhibiting erythroid differentiation and inducing myeloid differentiation. Blood. 2006 Jun 1;107(11):4308-4316.
Wang, D.; D'Costa, J.; Civin, C.I.; Friedman, A.D. C/EBPalpha directs monocytic commitment of primary myeloid progenitors. Blood. 2006 Aug 15;108(4):1223-1229.
Yu, X.; Alder, J.K.; Chun, J.H.; Friedman, A.D.; Heimfeld, S.; Cheng, L.; Civin, C.I. HES1 inhibits cycling of hematopoietic progenitor cells via DNA binding. Stem Cells. 2006 Apr;24(4):876-888.
Zhang, L.; D'Costa, J.; Kummalue, T.; Civin, C.I.; Friedman, A.D. Identification of a region on the outer surface of the CBFbeta-SMMHC myeloid oncoprotein assembly competence domain critical for multimerization. Oncogene. 2006 Nov 23;25(55):7289-7296.
Friedman, A.D. C/EBPalpha induces PU.1 and interacts with AP-1 and NF-kappaB to regulate myeloid development. Blood cells, molecules & diseases. 2007 Nov-Dec;39(3):340-343.
Friedman, A.D. Normal and malignant hematopoiesis. Oncogene. 2007 Oct 15;26(47):6686.
Friedman, A.D. Transcriptional control of granulocyte and monocyte development. Oncogene. 2007 Oct 15;26(47):6816-6828.
Parker, J.B.; Bianchet, M.A.; Krosky, D.J.; Friedman, J.I.; Amzel, L.M.; Stivers, J.T. Enzymatic capture of an extrahelical thymine in the search for uracil in DNA. Nature. 2007 Sep 27;449(7161):433-437.
Yeamans, C.; Wang, D.; Paz-Priel, I.; Torbett, B.E.; Tenen, D.G.; Friedman, A.D. C/EBPalpha binds and activates the PU.1 distal enhancer to induce monocyte lineage commitment. Blood. 2007 Nov 1;110(9):3136-3142.
Brem, S.S.; Bierman, P.J.; Black, P.; Brem, H.; Chamberlain, M.C.; Chiocca, E.A.; DeAngelis, L.M.; Fenstermaker, R.A.; Friedman, A.; Gilbert, M.R.; Glass, J.; Grossman, S.A.; Heimberger, A.B.; Junck, L.; Linette, G.P.; Loeffler, J.J.; Maor, M.H.; Moots, P.; Mrugala, M.; Nabors, L.B.; Newton, H.B.; Olivi, A.; Portnow, J.; Prados, M.; Raizer, J.J.; Shrieve, D.C.; Sills, A.K., Jr. Central nervous system cancers. Journal of the National Comprehensive Cancer Network : JNCCN. 2008 May;6(5):456-504.
Cai, D.H.; Wang, D.; Keefer, J.; Yeamans, C.; Hensley, K.; Friedman, A.D. C/EBP alpha:AP-1 leucine zipper heterodimers bind novel DNA elements, activate the PU.1 promoter and direct monocyte lineage commitment more potently than C/EBP alpha homodimers or AP-1. Oncogene. 2008 Apr 24;27(19):2772-2779.
Kuo, D.Z.; Milstone, A.M.; Omokaro, S.O.; Friedman, A.D.; Karanjawala, Z.E.; Borowitz, M.; Joyner, M.L.; Halsey, N.A.; Sibinga, E.M. Epstein-Barr virus-associated central nervous system lymphoproliferative disease in a patient with acquired immunodeficiency syndrome responsive to highly active antiretroviral therapy. Clin Infect Dis. 2008 May 1;46(9):1476-1478.
Zhang, L.; Fried, F.B.; Guo, H.; Friedman, A.D. Cyclin-dependent kinase phosphorylation of RUNX1/AML1 on 3 sites increases transactivation potency and stimulates cell proliferation. Blood. 2008 Feb 1;111(3):1193-1200.
Friedman, A.D. Cell cycle and developmental control of hematopoiesis by Runx1. J Cell Physiol. 2009 Jun;219(3):520-524.
Friedman, J.I.; Majumdar, A.; Stivers, J.T. Nontarget DNA binding shapes the dynamic landscape for enzymatic recognition of DNA damage. Nucleic Acids Res. 2009 Jun;37(11):3493-3500.
Jack, G.D.; Zhang, L.; Friedman, A.D. M-CSF elevates c-Fos and phospho-C/EBPalpha(S21) via ERK whereas G-CSF stimulates SHP2 phosphorylation in marrow progenitors to contribute to myeloid lineage specification. Blood. 2009 Sep 3;114(10):2172-2180.
Paz-Priel, I.; Ghosal, A.K.; Kowalski, J.; Friedman, A.D. C/EBPalpha or C/EBPalpha oncoproteins regulate the intrinsic and extrinsic apoptotic pathways by direct interaction with NF-kappaB p50 bound to the bcl-2 and FLIP gene promoters. Leukemia. 2009 Feb;23(2):365-374.
Wang, D.; Paz-Priel, I.; Friedman, A.D. NF-kappa B p50 regulates C/EBP alpha expression and inflammatory cytokine-induced neutrophil production. J Immunol. 2009 May 1;182(9):5757-5762.
Yan, H.; Parsons, D.W.; Jin, G.; McLendon, R.; Rasheed, B.A.; Yuan, W.; Kos, I.; Batinic-Haberle, I.; Jones, S.; Riggins, G.J.; Friedman, H.; Friedman, A.; Reardon, D.; Herndon, J.; Kinzler, K.W.; Velculescu, V.E.; Vogelstein, B.; Bigner, D.D. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009 Feb 19;360(8):765-773.
Zhou, J.; Trock, B.; Tsangaris, T.N.; Friedman, N.B.; Shapiro, D.; Brotzman, M.; Chan-Li, Y.; Chan, D.W.; Li, J. A unique proteolytic fragment of alpha1-antitrypsin is elevated in ductal fluid of breast cancer patient. Breast Cancer Res Treat. 2009 Nov 10.
Chudova, D.; Wilde, J.I.; Wang, E.T.; Wang, H.; Rabbee, N.; Egidio, C.M.; Reynolds, J.; Tom, E.; Pagan, M.; Rigl, C.T.; Friedman, L.; Wang, C.C.; Lanman, R.B.; Zeiger, M.; Kebebew, E.; Rosai, J.; Fellegara, G.; LiVolsi, V.A.; Kennedy, G.C. Molecular classification of thyroid nodules using high-dimensionality genomic data. J Clin Endocrinol Metab. 2010 Dec;95(12):5296-5304.
Friedman, A.D. Erythroid maturation and proliferation arrest: The GATA-1 connection. Cell Cycle. 2010 Dec 14;9(10):1873-1877.
Friedman, J.I.; McMahon, M.T.; Stivers, J.T.; Van Zijl, P.C. Indirect detection of labile solute proton spectra via the water signal using frequency-labeled exchange (FLEX) transfer. J Am Chem Soc. 2010 Feb 17;132(6):1813-1815.
Friedman, J.I.; Stivers, J.T. Detection of damaged DNA bases by DNA glycosylase enzymes. Biochemistry. 2010 Jun 22;49(24):4957-4967.
Parsons, D.W.; Li, M.; Zhang, X.; Jones, S.; Leary, R.J.; Lin, J.C.; Boca, S.M.; Carter, H.; Samayoa, J.; Bettegowda, C.; Gallia, G.L.; Jallo, G.I.; Binder, Z.A.; Nikolsky, Y.; Hartigan, J.; Smith, D.R.; Gerhard, D.S.; Fults, D.W.; Vandenberg, S.; Berger, M.S.; Marie, S.K.; Shinjo, S.M.; Clara, C.; Phillips, P.C.; Minturn, J.E.; Biegel, J.A.; Judkins, A.R.; Resnick, A.C.; Storm, P.B.; Curran, T.; He, Y.; Rasheed, B.A.; Friedman, H.S.; Keir, S.T.; McLendon, R.; Northcott, P.A.; Taylor, M.D.; Burger, P.C.; Riggins, G.J.; Karchin, R.; Parmigiani, G.; Bigner, D.D.; Yan, H.; Papadopoulos, N.; Vogelstein, B.; Kinzler, K.W.; Velculescu, V.E. The Genetic Landscape of the Childhood Cancer Medulloblastoma. Science. 2010 Dec 16.
Wang, C.C.; Friedman, L.; Kennedy, G.C.; Wang, H.; Kebebew, E.; Steward, D.L.; Zeiger, M.A.; Westra, W.H.; Wang, Y.; Khanafshar, E.; Fellegara, G.; Rosai, J.; Livolsi, V.; Lanman, R.B. A Large Multicenter Correlation Study of Thyroid Nodule Cytopathology and Histopathology. Thyroid. 2010 Dec 29.
Friedman, J.I.; Jiang, Y.L.; Miller, P.S.; Stivers, J.T. Unique dynamic properties of DNA duplexes containing interstrand cross-links. Biochemistry. 2011 Feb 8;50(5):882-890.
Guo, H.; Friedman, A.D. Phosphorylation of RUNX1 by cyclin-dependent kinase reduces direct interaction with HDAC1 and HDAC3. J Biol Chem. 2011 Jan 7;286(1):208-215.
D'Costa J., Chaudhuri S., Civin C.I., and Friedman A.D. (2005). CBFb-SMMHC slows proliferation of primary murine and human myeloid progenitors. Leukemia 19:921-9.
Paz-Priel I., Cai D.H., Wang D., Kowalski J., Blackford A., Liu H., Heckman C.A., Gombart A., Koeffler HP, Boxer LM, and Friedman AD. (2005). C/EBPa and C/EBPa myeloid oncoproteins induce bcl-2 via interaction of their basic regions with NF-kB p50. Mol. Cancer Res. 3:585-96.
Wang D., D''Costa J., Civin C.I., and Friedman A.D. (2006). C/EBPa directs monocytic commitment of primary myeloid progenitors. Blood 108:1223-29.
Zhang L., D''Costa J., Kummalue T., Civin C.I., and Friedman A.D. (2006). Identification of a Region on the Outer Surface of the CBFb-SMMHC Myeloid Oncoprotein Assembly Competence Domain Critical for Multimerization. Oncogene 25:7289-96.
Yeamans C., Wang D., Paz-Priel I., Torbett B.E., Tenen D.G., and Friedman A.D. (2007). C/EBPa binds and activates the PU.1 distal enhancer to induce monocyte lineage commitment. Blood 110;3136-42.
Friedman, A. D. (2007). Transcriptional control of granulocyte and monocyte development. Oncogene 26:6816-28. (review).
Zhang L., Fried F.B., Guo H., and Friedman A.D. (2008). Cyclin-dependent kinase phosphorylation of RUNX1/AML1 on three sites increases trans-activation potency and stimulates cell proliferation. Blood 111:1193-1200.
Cai D.H., Wang D., Keefer J., Yeamans C., Hensley K., and Friedman A.D. (2008). C/EBPa:AP-1 leucine zipper heterodimers bind novel DNA element, activate the PU.1 promoter, and direct monocyte lineage commitment more potently Than C/EBPa homodimers or AP-1. Oncogene 27:2772-9.
Paz-Priel I., Ghosal A.K, Kowalski J., and Friedman A.D. (2009). C/EBP? or C/EBP? oncoproteins regulate the intrinsic and extrinsic apoptotic pathways by direct interaction with NF-kB p50 bound to the bcl-2 and FLIP gene promoters. Leukemia 23:365-74.
Wang D., Paz-Priel I., and Friedman A.D. (2009). NF-kB p50 regulates C/EBPa expression and inflammatory cytokine-induced neutrophil production. J. Immunol. 2009; 182:5757-62.
Friedman A,D. (2009). Cell cycle and development control of hematopoiesis by Runx1. J. Cell. Physiol. 219:520-524. (review).
Jack G.D, Zhang L., Friedman A.D. (2009). M-CSF elevates c-Fos and phospho-C/EBPa(S21) via ERK whereas G-CSF stimulates SHP2 phosphorylation in marrow progenitors to contribute to myeloid lineage specification. Blood,114:2172-80.
- hematopoiesis, leukemia
1990-American Association for the Advancement of Science
1994-American Society of Pediatric Hematology-Oncology
1994-American Society of Hematology
1996-American Academy of Pediatrics