Richard F. Ambinder, MD

Professional Titles

• Director, Division of Hematologic Malignancies
• Co-Leader, Hematologic Malignancies and Bone Marrow Transplantation Program (HMBMT)
• James B. Murphy Professor

Primary Academic Title

Professor of Oncology

Background

Centers and Institutes

Sidney Kimmel Comprehensive Cancer Center

Clinical Trial Keywords

Epstein-Barr Virus; Lymphoma; Kaposi's sarcoma

Clinical Trials Summary

Learn more about clinical trials at the Johns Hopkins Kimmel Cancer Center.

Additional Academic Titles

Professor of Pathology, Professor of Medicine, Professor of Pharmacology and Molecular Sciences

Contact for Research Inquiries

1650 Orleans Street,
Room 389
Baltimore, MD 21287

ambinder@jhu.edu

Research Interests

AIDS Associated Cancers, Antitumor therapy, Antiviral therapy, Epstein-Barr Virus and Cancer, Kaposi's Sarcoma, Lymphoma, Lymphoma biology, Virology in human cancer

Lab Website

Richard F. Ambinder Lab - Lab Website

• Epstein-Barr virus and Kaposi's sarcoma herpesvirus are found in association with a variety of cancers. Our laboratory studies are aimed at better defining the role(s) of the virus in the pathogenesis of these diseases and the development of strategies to prevent, diagnose or treat them. We have become particularly interested in the unfolded protein response in activation of latent viral infection. Among the notions that we are exploring is the possibility that activation of virus-encoded enzymes will allow the targeted delivery of radation. In addition, we are investigating a variety of virus-related biomarkers including viral DNA, antibody responses, and cytokine measurements that may be clinically relevant.

PubMed

http://www.ncbi.nlm.nih.gov/sites/myncbi/richard.ambinder.1/bibliography/44377751/public/?sort=date&direction=ascending

Selected Publications

• 1. Yang J, Lemas VM, Flinn IW, Krone C, Ambinder RF. Application of the ELISPOT Assay to the Characterization of CD8+ Responses to Epstein-Barr Virus Antigens. Blood 95:241-248, 2000. (PMID: 10607708)
  2. Cannon JS, Ciufo D, Hawkins AL, Griffin CA, Borowitz MJ, Hayward GS and Ambinder RF. A New Primary Effusion Lymphoma - Derived Cell Line Yields Highly Infectious Kaposis Sarcoma Herpesvirus Supernatant. J Virol, 74:10187-10193, 2000. (PMID: 11024147)
  3. Yang J, Tao Q, Flinn IW, Murray PG, Post LE, Ma H, Piantadosi S, Caligiuri MA, Ambinder RF. Characterization of Epstein Barr Virus-infected B Cells in Patients with Posttransplantation Lymphoproliferative Disease: Disappearance after Rituximab Therapy does not Predict Clinical Response. Blood, 96:4055-4063, 2000. (PMID: 11110673)
  4. Flinn IW, ODonnell PV, Goodrich A, Vogelsang G, Abrams R, Noga S, Marcellus D, Borowitz M, Jones R, Ambinder RF. Immunotherapy with Rituximab during Peripheral Blood Stem Cell Transplantation for Non-Hodgkins Lymphoma. Biology of Blood and Marrow Transplantation, 6:628-632, 2000. (PMID: 11128813)
  5. Moore SM, Cannon JS, Tanhehco YC, Hamzeh FM, Ambinder RF. Induction of Epstein-Barr Virus Kinases to Sensitize Tumor Cells to Nucleoside Analogues. Antimicrob Agents Chemother. 45:2082-2091, 2001. (PMID: 11408227)
  6. Glaser SL, Clarke CA, Gulley ML, Craig FE, DiGiuseppe JA, Dorfman RF, Mann RB, Ambinder RF. Population-Based Patterns of Human Immunodeficiency Virus-Related Hodgkin Lymphoma in the Greater San Francisco Bay Area. Cancer, 98:300-309, 2003. (PMID: 12872349)
  7. Chan AT, Tao Q, Robertson KD, Flinn IW, Mann RB, Klencke B, Kwan WH, Leung TW, Johnson PJ, Ambinder RF. Azacitidine Induces Demethylation of the Epstein-Barr Virus Genome in Tumors in Patients. J Clin Oncol: 22: 1373-81, 2004. (PMID: 15007085)
  8. Glaser SL, Keegan THM, Clarke CA, Trinh M, Dorfman RF, Mann RB, DiGiuseppe JA, Ambinder RF. Exposure to Childhood Infections and Risk of Epstein-Barr Virus-Defined Hodgkins Lymphoma in Women. Int J Cancer 115 : 599-605, 2005. (PMID: 15700307)
  9. Keegan TH, Glaser SL, Clarke CA, Gulley ML, Craig FE, Digiuseppe JA, Dorfman RF, Mann RB, Ambinder RF. Epstein Barr Virus as a Marker of Survival after Hodgkin's Lymphoma: a Population Based Study. J Clin Oncol. 23: 7604 13, 2005. (PMID: 16186595)
  10. Keegan TH, Glaser SL, Clarke CA, Dorfman RF, Mann RB, DiGiuseppe JA, Chang ET, Ambinder RF. Body Size, Physical Activity, and Risk of Hodgkin's Lymphoma in Women. Cancer Epidemiology Biomarkers & Prevention 15:1095-1101, 2006. (PMID: 16775165)
  11. Fu D X, Tanhehco YC, Chen J, Foss CA, Fox JJ, Lemas V, Chong JM, Ambinder R F, Pomper MG. Virus-Associated Tumor Imaging by Induction of Viral Gene Expression. Clin Cancer Res. 13: 1453-8, 2007. (PMID: 17332288)
  12. Glaser SL, Gully ML, Clarke CA, Keegan TH, Chang ET, Shema SJ, Craig FE, DiGiuseppe JA, Dorfman RF, Mann RB, Culver HA, Coszen W, Ambinder, RF. Racial/Ethnic Variation in EBV-Positive Classical Hodgkin Lymphoma in California Populations. Int J Cancer. 123:1499-1507, 2008. (PMID: 18646185)
  13. Fu D, Tanhehco Y, Chen J, Foss CA, Fos JF, Chong J, Hobbs RF, Fukayama M, Sgouros G, Kowalski J, Pomper MG, Ambinder RF. Bortezomib-Induced Enzyme-Targeted Radiotherapy in Herpesvirus-Associated Tumors. Nat Med. 14:1118-22, 2008. (PMID: 18776891)
  14. Jones RJ, Gocke CD, Kasamon YL, Miller CB, Perkins B, Barber JP, Vala MS, Gerber JM, Gellert LL, Siedner M, Lemas MV, Brennan S, Ambinder RF, Matsui W. Circulating Clonotypic B Cells in Classical Hodgkin's Lymphoma. Blood .113:5920-6, 2009. (PMID: 19188663)
  15. Lin L, Lee JY, Kaplan LD, Dezube BJ, Noy A, Krown SE, Levine AM, Yu Y, Hayward GS, Ambinder RF. Effects of Chemotherapy in AIDS-Associated Non-Hodgkins Lymphoma on KSHV DNA in Blood. J Clin Oncol. 27: 2496-502, 2009. (PMID: 1934954)
  16. Aksentijevich, I.; Jones, R.J.; Ambinder, R.F.; Garrett-Mayer, E.; Flinn, I.W. Clinical outcome following autologous and allogeneic blood and marrow transplantation for relapsed diffuse large-cell non-Hodgkin's lymphoma. Biol Blood Marrow Transplant. 2006 Sep;12(9):965-972.
  17. Ambinder, R.F. Epstein-Barr virus and HIV. In: Tselis, A.; Jenson, H.B., editors, Epstein-Barr Virus. New York, NY: Taylor and Francis Group; 2006.
  18. Huff, C.A.; Fuchs, E.J.; Smith, B.D.; Blackford, A.; Garrett-Mayer, E.; Brodsky, R.A.; Flinn, I.W.; Ambinder, R.F.; Borrello, I.M.; Matsui, W.H.; Vogelsang, G.B.; Griffin, C.A.; Luznik, L.; Jones, R.J. Graft-versus-host reactions and the effectiveness of donor lymphocyte infusions. Biol Blood Marrow Transplant. 2006 Apr;12(4):414-421.
  19. Keegan, T.H.; Glaser, S.L.; Clarke, C.A.; Dorfman, R.F.; Mann, R.B.; DiGiuseppe, J.A.; Chang, E.T.; Ambinder, R.F. Body size, physical activity, and risk of Hodgkin's lymphoma in women. Cancer Epidemiol Biomarkers Prev. 2006 Jun;15(6):1095-1101.
  20. Krown, S.E.; Lee, J.Y.; Lin, L.; Fischl, M.A.; Ambinder, R.; Von Roenn, J.H. Interferon-alpha2b with protease inhibitor-based antiretroviral therapy in patients with AIDS-associated Kaposi sarcoma: an AIDS malignancy consortium phase I trial. J Acquir Immune Defic Syndr. 2006 Feb 1;41(2):149-153.
  21. Ambinder, R.F. Epstein-barr virus and hodgkin lymphoma. Hematology / the Education Program of the American Society of Hematology American Society of Hematology. 2007;2007:204-209.
  22. Berdeja, J.G.; Hess, A.; Lucas, D.M.; O'Donnell, P.; Ambinder, R.F.; Diehl, L.F.; Carter-Brookins, D.; Newton, S.; Flinn, I.W. Systemic interleukin-2 and adoptive transfer of lymphokine-activated killer cells improves antibody-dependent cellular cytotoxicity in patients with relapsed B-cell lymphoma treated with rituximab. Clin Cancer Res. 2007 Apr 15;13(8):2392-2399.
  23. Bolanos-Meade, J.; Garrett-Mayer, E.; Luznik, L.; Anders, V.; Webb, J.; Fuchs, E.J.; Huff, C.A.; Matsui, W.; Borrello, I.M.; Brodsky, R.; Kasamon, Y.L.; Swinnen, L.J.; Flinn, I.W.; Ambinder, R.F.; Jones, R.J.; Hess, A.D.; Vogelsang, G.B. Induction of autologous graft-versus-host disease: results of a randomized prospective clinical trial in patients with poor risk lymphoma. Biol Blood Marrow Transplant. 2007 Oct;13(10):1185-1191.
  24. Epeldegui, M.; Hung, Y.P.; McQuay, A.; Ambinder, R.F.; Martinez-Maza, O. Infection of human B cells with Epstein-Barr virus results in the expression of somatic hypermutation-inducing molecules and in the accrual of oncogene mutations. Mol Immunol. 2007 Feb;44(5):934-942.
  25. Fu, D.X.; Tanhehco, Y.C.; Chen, J.; Foss, C.A.; Fox, J.J.; Lemas, V.; Chong, J.M.; Ambinder, R.F.; Pomper, M.G. Virus-associated tumor imaging by induction of viral gene expression. Clin Cancer Res. 2007 Mar 1;13(5):1453-1458.
  26. Seng, T.J.; Low, J.S.; Li, H.; Cui, Y.; Goh, H.K.; Wong, M.L.; Srivastava, G.; Sidransky, D.; Califano, J.; Steenbergen, R.D.; Rha, S.Y.; Tan, J.; Hsieh, W.S.; Ambinder, R.F.; Lin, X.; Chan, A.T.; Tao, Q. The major 8p22 tumor suppressor DLC1 is frequently silenced by methylation in both endemic and sporadic nasopharyngeal, esophageal, and cervical carcinomas, and inhibits tumor cell colony formation. Oncogene. 2007 Feb 8;26(6):934-944.
  27. Ying, J.; Gao, Z.; Li, H.; Srivastava, G.; Murray, P.G.; Goh, H.K.; Lim, C.Y.; Wang, Y.; Marafioti, T.; Mason, D.Y.; Ambinder, R.F.; Chan, A.T.; Tao, Q. Frequent epigenetic silencing of protocadherin 10 by methylation in multiple haematologic malignancies. Br J Haematol. 2007 Mar;136(6):829-832.
  28. Ying, J.; Li, H.; Murray, P.; Gao, Z.; Chen, Y.W.; Wang, Y.; Lee, K.Y.; Chan, A.T.; Ambinder, R.F.; Srivastava, G.; Tao, Q. Tumor-specific methylation of the 8p22 tumor suppressor gene DLC1 is an epigenetic biomarker for Hodgkin, nasal NK/T-cell and other types of lymphomas. Epigenetics. 2007 Jan-Mar;2(1):15-21.
  29. Fu, D.X.; Foss, C.A.; Nimmagadda, S.; Ambinder, R.F.; Pomper, M.G. Imaging virus-associated cancer. Current pharmaceutical design. 2008;14(28):3048-3065.
  30. Fu, D.-X.; Tanhehco, Y.; Chen, J.; Foss, C.A.; Fox, J.J.; Chong, J.-M.; Hobbs, R.F.; Fukayama, M.; Sgouros, G.; Kowalski, J.; Pomper, M.G.; Ambinder, R.F. Bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors. Nat Med (N Y, NY, U S). 2008;14(10):1118-1122.
  31. Kasamon, Y.L.; Ambinder, R.F. Immunotherapies for Hodgkin's lymphoma. Critical reviews in oncology/hematology. 2008 May;66(2):135-144.
  32. Luznik, L.; O'Donnell, P.V.; Symons, H.J.; Chen, A.R.; Leffell, M.S.; Zahurak, M.; Gooley, T.A.; Piantadosi, S.; Kaup, M.; Ambinder, R.F.; Huff, C.A.; Matsui, W.; Bolanos-Meade, J.; Borrello, I.; Powell, J.D.; Harrington, E.; Warnock, S.; Flowers, M.; Brodsky, R.A.; Sandmaier, B.M.; Storb, R.F.; Jones, R.J.; Fuchs, E.J. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008 Jun;14(6):641-650.
  33. Matsui, W.; Wang, Q.; Barber, J.P.; Brennan, S.; Smith, B.D.; Borrello, I.; McNiece, I.; Lin, L.; Ambinder, R.F.; Peacock, C.; Watkins, D.N.; Huff, C.A.; Jones, R.J. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res. 2008 Jan 1;68(1):190-197.
  34. Perkins, E.M.; Anacker, D.; Davis, A.; Sankar, V.; Ambinder, R.F.; Desai, P. Small capsid protein pORF65 is essential for assembly of Kaposi's sarcoma-associated herpesvirus capsids. J Virol. 2008 Jul;82(14):7201-7211.
  35. Spitzer, T.R.; Ambinder, R.F.; Lee, J.Y.; Kaplan, L.D.; Wachsman, W.; Straus, D.J.; Aboulafia, D.M.; Scadden, D.T. Dose-reduced busulfan, cyclophosphamide, and autologous stem cell transplantation for human immunodeficiency virus-associated lymphoma: AIDS Malignancy Consortium study 020. Biol Blood Marrow Transplant. 2008 Jan;14(1):59-66.
  36. Wagner-Johnston, N.D.; Ambinder, R.F. Blood and marrow transplant for lymphoma patients with HIV/AIDS. Curr Opin Oncol. 2008 Mar;20(2):201-205.
  37. Warlick, E.D.; O'Donnell, P.V.; Borowitz, M.; Grupka, N.; Decloe, L.; Garrett-Mayer, E.; Borrello, I.; Brodsky, R.; Fuchs, E.; Huff, C.A.; Luznik, L.; Matsui, W.; Ambinder, R.; Jones, R.J.; Douglas Smith, B. Myeloablative allogeneic bone marrow transplant using T cell depleted allografts followed by post-transplant GM-CSF in high-risk myelodysplastic syndromes. Leuk Res. 2008 Sep;32(9):1439-1447.
  38. Aissani, B.; Ogwaro, K.M.; Shrestha, S.; Tang, J.; Breen, E.C.; Wong, H.L.; Jacobson, L.P.; Rabkin, C.S.; Ambinder, R.F.; Martinez-Maza, O.; Kaslow, R.A. The major histocompatibility complex conserved extended haplotype 8.1 in AIDS-related non-Hodgkin lymphoma. J Acquir Immune Defic Syndr. 2009 Oct 1;52(2):170-179.
  39. Ambinder, R.F. The same but different: autologous hematopoietic stem cell transplantation for patients with lymphoma and HIV infection. Bone Marrow Transplant. 2009 Jul;44(1):1-5.
  40. Ambinder, R.F. Evaluation of T- and NK-cell-targeted therapies: is there a role for rituximab prophylaxis? Clin Cancer Res. 2009 Apr 1;15(7):2205-2206.
  41. Ambinder, R.F.; Hayward, S.D. Kaposis Sarcoma. In: Lang, F., editor, Encyclopedia of Molecular Mechanisms of Disease: Springer-Verlag 2009. p. 1110-1112.
  42. Bolanos-Meade, J.; Luznik, L.; Muth, M.; Matsui, W.H.; Huff, C.A.; Smith, B.D.; Levy, M.Y.; Kasamon, Y.L.; Swinnen, L.J.; Powell, J.D.; Brodsky, R.A.; Ambinder, R.F.; Jones, R.J.; Fuchs, E.J. Salvage transplantation for allograft failure using fludarabine and alemtuzumab as conditioning regimen. Bone Marrow Transplant. 2009 Mar;43(6):477-480.
  43. Chang, E.T.; Birmann, B.M.; Kasperzyk, J.L.; Conti, D.V.; Kraft, P.; Ambinder, R.F.; Zheng, T.; Mueller, N.E. Polymorphic variation in NFKB1 and other aspirin-related genes and risk of Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev. 2009 Mar;18(3):976-986.
  44. Fuchs, E.J.; Luznik, L.; Bolanos-Meade, J.; Miller, C.B.; Brodsky, R.A.; Ambinder, R.F.; Jones, R.J. Successful pregnancy and childbirth after reduced-intensity conditioning and partially HLA-mismatched BMT. Bone Marrow Transplant. 2009 Jun;43(12):969-970.
  45. Jones, R.J.; Gocke, C.D.; Kasamon, Y.L.; Miller, C.B.; Perkins, B.; Barber, J.P.; Vala, M.S.; Gerber, J.M.; Gellert, L.L.; Siedner, M.; Lemas, M.V.; Brennan, S.; Ambinder, R.F.; Matsui, W. Circulating clonotypic B cells in classic Hodgkin lymphoma. Blood. 2009 Jun 4;113(23):5920-5926.
  46. Kasamon, Y.L.; Luznik, L.; Leffell, M.S.; Kowalski, J.; Tsai, H.L.; Bolanos-Meade, J.; Morris, L.E.; Crilley, P.A.; O'Donnell, P.V.; Rossiter, N.; Huff, C.A.; Brodsky, R.A.; Matsui, W.H.; Swinnen, L.J.; Borrello, I.; Powell, J.D.; Ambinder, R.F.; Jones, R.J.; Fuchs, E.J. Nonmyeloablative HLA-Haploidentical BMT with High-Dose Posttransplantation Cyclophosphamide: Effect of HLA Disparity on Outcome. Biol Blood Marrow Transplant. 2009 Nov 16.
  47. Kasamon, Y.L.; Wahl, R.L.; Ziessman, H.A.; Blackford, A.L.; Goodman, S.N.; Fidyk, C.A.; Rogers, K.M.; Bolanos-Meade, J.; Borowitz, M.J.; Ambinder, R.F.; Jones, R.J.; Swinnen, L.J. Phase II study of risk-adapted therapy of newly diagnosed, aggressive non-Hodgkin lymphoma based on midtreatment FDG-PET scanning. Biol Blood Marrow Transplant. 2009 Feb;15(2):242-248.
  48. Lechowicz, M.; Dittmer, D.P.; Lee, J.Y.; Krown, S.E.; Wachsman, W.; Aboulafia, D.; Dezube, B.J.; Ratner, L.; Said, J.; Ambinder, R.F. Molecular and clinical assessment in the treatment of AIDS Kaposi sarcoma with valproic Acid. Clin Infect Dis. 2009 Dec 15;49(12):1946-1949.
  49. Lin, J.; Gilbert, J.; Rudek, M.A.; Zwiebel, J.A.; Gore, S.; Jiemjit, A.; Zhao, M.; Baker, S.D.; Ambinder, R.F.; Herman, J.G.; Donehower, R.C.; Carducci, M.A. A phase I dose-finding study of 5-azacytidine in combination with sodium phenylbutyrate in patients with refractory solid tumors. Clin Cancer Res. 2009 Oct 1;15(19):6241-6249.
  50. Lin, L.; Lee, J.Y.; Kaplan, L.D.; Dezube, B.J.; Noy, A.; Krown, S.E.; Levine, A.M.; Yu, Y.; Hayward, G.S.; Ambinder, R.F. Effects of chemotherapy in AIDS-associated non-Hodgkin's lymphoma on Kaposi's sarcoma herpesvirus DNA in blood. J Clin Oncol. 2009 May 20;27(15):2496-2502.
  51. Ratner, L.; Harrington, W.; Feng, X.; Grant, C.; Jacobson, S.; Noy, A.; Sparano, J.; Lee, J.; Ambinder, R.; Campbell, N.; Lairmore, M.; Consortium, A.M. Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma. PLoS One. 2009;4(2):e4420.
  52. Ambinder, R.F. Mystery of the missing target. Blood. 2010 Nov 11;116(19):3691-3692.
  53. Ambinder, R.F.; Bhatia, K.; Martinez-Maza, O.; Mitsuyasu, R. Cancer biomarkers in HIV patients. Curr Opin HIV AIDS. 2010 Nov;5(6):531-537.
  54. Brodsky, R.A.; Chen, A.R.; Dorr, D.; Fuchs, E.J.; Huff, C.A.; Luznik, L.; Smith, B.D.; Matsui, W.H.; Goodman, S.N.; Ambinder, R.F.; Jones, R.J. High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up. Blood. 2010 Mar 18;115(11):2136-2141.
  55. Kasamon, Y.L.; Jones, R.J.; Brodsky, R.A.; Fuchs, E.J.; Matsui, W.; Luznik, L.; Powell, J.D.; Blackford, A.L.; Goodrich, A.; Gocke, C.D.; Abrams, R.A.; Ambinder, R.F.; Flinn, I.W. Immunologic recovery following autologous stem-cell transplantation with pre- and posttransplantation rituximab for low-grade or mantle cell lymphoma. Ann Oncol. 2010 Jun;21(6):1203-1210.
  56. Kasamon, Y.L.; Jones, R.J.; Gocke, C.D.; Blackford, A.L.; Seifter, E.J.; Davis-Sproul, J.M.; Gore, S.D.; Ambinder, R.F. Extended Follow-Up of Autologous Bone Marrow Transplantation with 4-Hydroperoxycyclophosphamide (4-HC) Purging for Indolent or Transformed Non-Hodgkin's Lymphomas. Biol Blood Marrow Transplant. 2010 Jul 21.
  57. Kasamon, Y.L.; Luznik, L.; Leffell, M.S.; Kowalski, J.; Tsai, H.L.; Bolanos-Meade, J.; Morris, L.E.; Crilley, P.A.; O'Donnell, P.V.; Rossiter, N.; Huff, C.A.; Brodsky, R.A.; Matsui, W.H.; Swinnen, L.J.; Borrello, I.; Powell, J.D.; Ambinder, R.F.; Jones, R.J.; Fuchs, E.J. Nonmyeloablative HLA-haploidentical bone marrow transplantation with high-dose posttransplantation cyclophosphamide: effect of HLA disparity on outcome. Biol Blood Marrow Transplant. 2010 Apr;16(4):482-489.
  58. Luznik, L.; Bolanos-Meade, J.; Zahurak, M.; Chen, A.R.; Smith, B.D.; Brodsky, R.; Huff, C.A.; Borrello, I.; Matsui, W.; Powell, J.D.; Kasamon, Y.; Goodman, S.N.; Hess, A.; Levitsky, H.I.; Ambinder, R.F.; Jones, R.J.; Fuchs, E.J. High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Blood. 2010 Apr 22;115(16):3224-3230.
  59. Shamay, M.; Greenway, M.; Liao, G.; Ambinder, R.F.; Hayward, S.D. De novo DNA methyltransferase DNMT3b interacts with NEDD8-modified proteins. J Biol Chem. 2010 Nov 19;285(47):36377-36386.

Graduate Program Affiliations

• BCMB Program
  Cellular and Molecular Medicine Graduate Program