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Rafael Bejar

Title(s)Associate Professor Of Clinical, Medicine
SchoolHealth Sciences
Phone858-534-5204
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    Collapse Overview 
    Collapse Overview
    Research Interests
    Our lab is focused on understanding the genetic changes that drive the development and progression of hematologic malignancies like acute myeloid leukemia and myelodysplastic syndromes. Our goal is to translate our discoveries into clinically meaningful improvements in how we care for patients with these disorders.

    Our prior work helped characterize the range of genetic alterations that exist in patients with myelodysplastic syndromes (MDS). We studied bone marrow sample from over 400 patients with these disorders and examined them for mutations in over 20 recurrently mutated genes. We learned about the relative frequency of these mutations, how they can overlap with each other, and how they may better classify molecular subtypes of MDS. We demonstrated that mutations in several genes are associated with clinical features seen in patients with MDS, potentially explaining much of the heterogeneity associated with this disease. Most importantly, we identified mutations in several genes, that when present, are associated with a poorer prognosis than would otherwise be predicted using standard clinical scoring systems. This has helped accelerate the drive to include tumor sequencing in the standard evaluation of patients with MDS.

    Currently we are investigating how acquired mutations in the diseased cells from patients with myelodysplastic syndromes are associated with their response to treatment with drugs like azacitidine and decitabine. We hope to discover genes that physicians can test for mutations in order to select the best treatment options for their patients with MDS. These studies should also give us insight into the mechanisms of drug resistance and how we may be able to overcome them.

    In addition, we are interested in the functional consequence of the mutations we have characterized in patients with MDS. For example, we are studying how mutations in the EZH2 gene, which are associated with a poor prognosis, might affect the function neutrophils in patients with these abnormalities.

    Going forward, we plan to implement clinical sequencing of bone marrow specimens from patients with MDS and related hematologic malignancies. Our plan is work out how best to use this information to personalize the choice of therapy and overall care of our patients with these disorders.

    Benjamin Ebert, David Steensma, Guillermo Garcia Manero, and their colleagues at the Brigham and Women’s Hospital, the Dana-Farber Cancer Institute, and the MD Anderson Cancer Center – Examination of mutations that may predict response to hypomethylating agents in patients with MDS.
    Nancy Huang and Anjana Rao – La Jolla Institute for Allergy and Immunology – Examination of 5-hydroxymethycytosine in MDS.
    Derek Murphy and Mike Makrigiorgos – Dana-Farber Cancer Institute – High sensitivity methods for detecting rare, but clinically important mutations.

    Education and Training
    MD, PhD - University of California, San Diego, La Jolla, CA - 2003
    Internal Medicine Internship - University of Chicago Hospitals, Chicago, IL - 2003-2004
    Internal Medicine Residency - Brigham and Women's Hospital, Boston, MA - 2004-2006
    Hematology/Oncology Fellowship - Dana Farber Partners Cancer Care, Boston, MA - 2006-2011
    Post-Doctoral Research - Brigham and Women's Hospital, Boston, MA - 2008-2012

    Collapse Research 
    Collapse Research Activities and Funding
    Characterization of Genetic Abnormalities in MDS and Their Clinical Impact
    NIH/NIDDK K08DK091360Apr 2, 2012 - Jan 31, 2017
    Role: Principal Investigator

    Collapse ORNG Applications 
    Collapse Clinical Trials
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    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
    List All   |   Timeline
    1. Reilly B, Tanaka TN, Diep D, Yeerna H, Tamayo P, Zhang K, Bejar R. DNA methylation identifies genetically and prognostically distinct subtypes of myelodysplastic syndromes. Blood Adv. 2019 Oct 08; 3(19):2845-2858. PMID: 31582393.
      View in: PubMed
    2. Stoner SA, Yan M, Liu KTH, Arimoto KI, Shima T, Wang HY, Johnson DT, Bejar R, Jamieson C, Guan KL, Zhang DE. Hippo Kinase Loss Contributes to Del(20q) Hematologic Malignancies through Chronic Innate Immune Activation. Blood. 2019 Aug 21. PMID: 31434702.
      View in: PubMed
    3. Bell JA, Galaznik A, Pompilus F, Strzok S, Bejar R, Scipione F, Fram RJ, Faller DV, Cano S, Marquis P. A pragmatic patient-reported outcome strategy for rare disease clinical trials: application of the EORTC item library to myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. J Patient Rep Outcomes. 2019 Jun 19; 3(1):35. PMID: 31218454.
      View in: PubMed
    4. Sekeres MA, Gore SD, Stablein DM, DiFronzo N, Abel GA, DeZern AE, Troy JD, Rollison DE, Thomas JW, Waclawiw MA, Liu JJ, Al Baghdadi T, Walter MJ, Bejar R, Gorak EJ, Starczynowski DT, Foran JM, Cerhan JR, Moscinski LC, Komrokji RS, Deeg HJ, Epling-Burnette PK. The National MDS Natural History Study: design of an integrated data and sample biorepository to promote research studies in myelodysplastic syndromes. Leuk Lymphoma. 2019 May 21; 1-11. PMID: 31111762.
      View in: PubMed
    5. Adelman ER, Huang HT, Roisman A, Olsson A, Colaprico A, Qin T, Lindsley RC, Bejar R, Salomonis N, Grimes HL, Figueroa ME. Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia. Cancer Discov. 2019 May 13. PMID: 31085557.
      View in: PubMed
    6. Pollyea DA, Harris C, Rabe JL, Hedin BR, De Arras L, Katz S, Wheeler E, Bejar R, Walter MJ, Jordan CT, Pietras EM, Alper S. Myelodysplastic syndrome-associated spliceosome gene mutations enhance innate immune signaling. Haematologica. 2019 Mar 07. PMID: 30846499.
      View in: PubMed
    7. Tanaka TN, Bejar R. MDS overlap disorders and diagnostic boundaries. Blood. 2019 Mar 07; 133(10):1086-1095. PMID: 30670443.
      View in: PubMed
    8. Haase D, Stevenson KE, Neuberg D, Maciejewski JP, Nazha A, Sekeres MA, Ebert BL, Garcia-Manero G, Haferlach C, Haferlach T, Kern W, Ogawa S, Nagata Y, Yoshida K, Graubert TA, Walter MJ, List AF, Komrokji RS, Padron E, Sallman D, Papaemmanuil E, Campbell PJ, Savona MR, Seegmiller A, Adès L, Fenaux P, Shih LY, Bowen D, Groves MJ, Tauro S, Fontenay M, Kosmider O, Bar-Natan M, Steensma D, Stone R, Heuser M, Thol F, Cazzola M, Malcovati L, Karsan A, Ganster C, Hellström-Lindberg E, Boultwood J, Pellagatti A, Santini V, Quek L, Vyas P, Tüchler H, Greenberg PL, Bejar R. TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups. Leukemia. 2019 Jan 11. PMID: 30635634.
      View in: PubMed
    9. Galanina N, Bejar R, Choi M, Goodman A, Wieduwilt M, Mulroney C, Kim L, Yeerna H, Tamayo P, Vergilio JA, Mughal TI, Miller V, Jamieson C, Kurzrock R. Comprehensive Genomic Profiling Reveals Diverse but Actionable Molecular Portfolios across Hematologic Malignancies: Implications for Next Generation Clinical Trials. Cancers (Basel). 2018 Dec 21; 11(1). PMID: 30583461.
      View in: PubMed
    10. Bolton KL, Gillis NK, Coombs CC, Takahashi K, Zehir A, Bejar R, Garcia-Manero G, Futreal A, Jensen BC, Diaz LA, Gupta D, Mantha S, Klimek V, Papaemmanuil E, Levine R, Padron E. Managing Clonal Hematopoiesis in Patients With Solid Tumors. J Clin Oncol. 2019 Jan 01; 37(1):7-11. PMID: 30403571.
      View in: PubMed
    11. Bejar R. What biologic factors predict for transformation to AML? Best Pract Res Clin Haematol. 2018 12; 31(4):341-345. PMID: 30466744.
      View in: PubMed
    12. Wang HY, Dell'Aquila ML, Dvanajscak Z, Bejar R, Broome HE, Hsi E, Murray SS, Thorson JA. JAK2 double minutes with resultant simultaneous amplification of JAK2 and CD274 in a therapy-related myelodysplastic syndrome evolving into an acute myeloid leukaemia. Br J Haematol. 2018 Aug 21. PMID: 30132795.
      View in: PubMed
    13. Park SJ, Bejar R. Clonal Hematopoiesis in Aging. Curr Stem Cell Rep. 2018 Sep; 4(3):209-219. PMID: 30854305.
      View in: PubMed
    14. Ozturk K, Dow M, Carlin DE, Bejar R, Carter H. The Emerging Potential for Network Analysis to Inform Precision Cancer Medicine. J Mol Biol. 2018 Sep 14; 430(18 Pt A):2875-2899. PMID: 29908887.
      View in: PubMed
    15. Padron E, Ball MC, Teer JK, Painter JS, Yoder SJ, Zhang C, Zhang L, Moscinski LC, Rollison DE, Gore SD, Bejar R, Walter MJ, Sekeres MA, Komrokji RS, Epling-Burnette PK. Germ line tissues for optimal detection of somatic variants in myelodysplastic syndromes. Blood. 2018 May 24; 131(21):2402-2405. PMID: 29661788.
      View in: PubMed
    16. Nazha A, Bejar R. Molecular Data and the IPSS-R: How Mutational Burden Can Affect Prognostication in MDS. Curr Hematol Malig Rep. 2017 10; 12(5):461-467. PMID: 28844082.
      View in: PubMed
    17. Sallman DA, Tanaka TN, List A, Bejar R. SOHO State of the Art Update and Next Questions: Biology and Treatment of Myelodysplastic Syndromes. Clin Lymphoma Myeloma Leuk. 2017 10; 17(10):613-620. PMID: 29025689.
      View in: PubMed
    18. Bejar R. Implications of molecular genetic diversity in myelodysplastic syndromes. Curr Opin Hematol. 2017 03; 24(2):73-78. PMID: 27875374.
      View in: PubMed
    19. Greenberg PL, Stone RM, Al-Kali A, Barta SK, Bejar R, Bennett JM, Carraway H, De Castro CM, Deeg HJ, DeZern AE, Fathi AT, Frankfurt O, Gaensler K, Garcia-Manero G, Griffiths EA, Head D, Horsfall R, Johnson RA, Juckett M, Klimek VM, Komrokji R, Kujawski LA, Maness LJ, O'Donnell MR, Pollyea DA, Shami PJ, Stein BL, Walker AR, Westervelt P, Zeidan A, Shead DA, Smith C. Myelodysplastic Syndromes, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017 01; 15(1):60-87. PMID: 28040720.
      View in: PubMed
    20. Haider M, Duncavage EJ, Afaneh KF, Bejar R, List AF. New Insight Into the Biology, Risk Stratification, and Targeted Treatment of Myelodysplastic Syndromes. Am Soc Clin Oncol Educ Book. 2017; 37:480-494. PMID: 28561687.
      View in: PubMed
    21. Bejar R, Greenberg PL. The Impact of Somatic and Germline Mutations in Myelodysplastic Syndromes and Related Disorders. J Natl Compr Canc Netw. 2017 01; 15(1):131-135. PMID: 28040723.
      View in: PubMed
    22. Drusbosky L, Medina C, Martuscello R, Hawkins KE, Chang M, Lamba JK, Vali S, Kumar A, Singh NK, Abbasi T, Sekeres MA, Mallo M, Sole F, Bejar R, Cogle CR. Computational drug treatment simulations on projections of dysregulated protein networks derived from the myelodysplastic mutanome match clinical response in patients. Leuk Res. 2017 01; 52:1-7. PMID: 27855285.
      View in: PubMed
    23. Steensma DP, Abedi M, Bejar R, Cogle CR, Foucar K, Garcia-Manero G, George TI, Grinblatt D, Komrokji R, Ma X, Maciejewski J, Pollyea DA, Savona MR, Scott B, Sekeres MA, Thompson MA, Swern AS, Nifenecker M, Sugrue MM, Erba H. Connect MDS/AML: design of the myelodysplastic syndromes and acute myeloid leukemia disease registry, a prospective observational cohort study. BMC Cancer. 2016 08 19; 16:652. PMID: 27538433.
      View in: PubMed
    24. Qiu J, Zhou B, Thol F, Zhou Y, Chen L, Shao C, DeBoever C, Hou J, Li H, Chaturvedi A, Ganser A, Bejar R, Zhang DE, Fu XD, Heuser M. Distinct splicing signatures affect converged pathways in myelodysplastic syndrome patients carrying mutations in different splicing regulators. RNA. 2016 10; 22(10):1535-49. PMID: 27492256.
      View in: PubMed
    25. Bejar R. Splicing Factor Mutations in Cancer. Adv Exp Med Biol. 2016; 907:215-28. PMID: 27256388.
      View in: PubMed
    26. Song C, Castellanos-Rizaldos E, Bejar R, Ebert BL, Makrigiorgos GM. DMSO Increases Mutation Scanning Detection Sensitivity of High-Resolution Melting in Clinical Samples. Clin Chem. 2015 Nov; 61(11):1354-62. PMID: 26432802.
      View in: PubMed
    27. Kwok B, Hall JM, Witte JS, Xu Y, Reddy P, Lin K, Flamholz R, Dabbas B, Yung A, Al-Hafidh J, Balmert E, Vaupel C, El Hader C, McGinniss MJ, Nahas SA, Kines J, Bejar R. MDS-associated somatic mutations and clonal hematopoiesis are common in idiopathic cytopenias of undetermined significance. Blood. 2015 Nov 19; 126(21):2355-61. PMID: 26429975.
      View in: PubMed
    28. Bejar R. Myelodysplastic Syndromes Diagnosis: What Is the Role of Molecular Testing? Curr Hematol Malig Rep. 2015 Sep; 10(3):282-91. PMID: 26126599.
      View in: PubMed
    29. Steensma DP, Bejar R, Jaiswal S, Lindsley RC, Sekeres MA, Hasserjian RP, Ebert BL. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015 Jul 02; 126(1):9-16. PMID: 25931582.
      View in: PubMed
    30. Greenberg PL, Stone RM, Bejar R, Bennett JM, Bloomfield CD, Borate U, De Castro CM, Deeg HJ, DeZern AE, Fathi AT, Frankfurt O, Gaensler K, Garcia-Manero G, Griffiths EA, Head D, Klimek V, Komrokji R, Kujawski LA, Maness LJ, O'Donnell MR, Pollyea DA, Scott B, Shami PJ, Stein BL, Westervelt P, Wheeler B, Shead DA, Smith C. Myelodysplastic syndromes, version 2.2015. J Natl Compr Canc Netw. 2015 Mar; 13(3):261-72. PMID: 25736003.
      View in: PubMed
    31. Sankaran VG, Ulirsch JC, Tchaikovskii V, Ludwig LS, Wakabayashi A, Kadirvel S, Lindsley RC, Bejar R, Shi J, Lovitch SB, Bishop DF, Steensma DP. X-linked macrocytic dyserythropoietic anemia in females with an ALAS2 mutation. J Clin Invest. 2015 Apr; 125(4):1665-9. PMID: 25705881.
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    32. Bejar R, Steensma DP. Recent developments in myelodysplastic syndromes. Blood. 2014 Oct 30; 124(18):2793-803. PMID: 25237199.
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    33. Schneider RK, Ademà V, Heckl D, Järås M, Mallo M, Lord AM, Chu LP, McConkey ME, Kramann R, Mullally A, Bejar R, Solé F, Ebert BL. Role of casein kinase 1A1 in the biology and targeted therapy of del(5q) MDS. Cancer Cell. 2014 Oct 13; 26(4):509-20. PMID: 25242043.
      View in: PubMed
    34. Bejar R, Lord A, Stevenson K, Bar-Natan M, Pérez-Ladaga A, Zaneveld J, Wang H, Caughey B, Stojanov P, Getz G, Garcia-Manero G, Kantarjian H, Chen R, Stone RM, Neuberg D, Steensma DP, Ebert BL. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood. 2014 Oct 23; 124(17):2705-12. PMID: 25224413.
      View in: PubMed
    35. Bejar R, Stevenson KE, Caughey B, Lindsley RC, Mar BG, Stojanov P, Getz G, Steensma DP, Ritz J, Soiffer R, Antin JH, Alyea E, Armand P, Ho V, Koreth J, Neuberg D, Cutler CS, Ebert BL. Somatic mutations predict poor outcome in patients with myelodysplastic syndrome after hematopoietic stem-cell transplantation. J Clin Oncol. 2014 Sep 01; 32(25):2691-8. PMID: 25092778.
      View in: PubMed
    36. Bejar R. Clinical and genetic predictors of prognosis in myelodysplastic syndromes. Haematologica. 2014 Jun; 99(6):956-64. PMID: 24881041.
      View in: PubMed
    37. Adema V, Bejar R. What lies beyond del(5q) in myelodysplastic syndrome? Haematologica. 2013 Dec; 98(12):1819-21. PMID: 24323981.
      View in: PubMed
    38. Bejar R, Abdel-Wahab O. The importance of subclonal genetic events in MDS. Blood. 2013 Nov 21; 122(22):3550-1. PMID: 24263953.
      View in: PubMed
    39. Bejar R. Prognostic models in myelodysplastic syndromes. Hematology Am Soc Hematol Educ Program. 2013; 2013:504-10. PMID: 24319225.
      View in: PubMed
    40. Bejar R, Tiu RV, Sekeres MA, Komrokji RS. Myelodysplastic syndromes: recent advancements in risk stratification and unmet therapeutic challenges. Am Soc Clin Oncol Educ Book. 2013. PMID: 23714517.
      View in: PubMed
    41. Bejar R, Stevenson KE, Caughey BA, Abdel-Wahab O, Steensma DP, Galili N, Raza A, Kantarjian H, Levine RL, Neuberg D, Garcia-Manero G, Ebert BL. Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromes. J Clin Oncol. 2012 Sep 20; 30(27):3376-82. PMID: 22869879.
      View in: PubMed
    42. Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G, Kantarjian H, Raza A, Levine RL, Neuberg D, Ebert BL. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011 Jun 30; 364(26):2496-506. PMID: 21714648.
      View in: PubMed
    43. Bejar R, Levine R, Ebert BL. Unraveling the molecular pathophysiology of myelodysplastic syndromes. J Clin Oncol. 2011 Feb 10; 29(5):504-15. PMID: 21220588.
      View in: PubMed
    44. Bejar R, Ebert BL. The genetic basis of myelodysplastic syndromes. Hematol Oncol Clin North Am. 2010 Apr; 24(2):295-315. PMID: 20359627.
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    45. Ikeda S, He A, Kong SW, Lu J, Bejar R, Bodyak N, Lee KH, Ma Q, Kang PM, Golub TR, Pu WT. MicroRNA-1 negatively regulates expression of the hypertrophy-associated calmodulin and Mef2a genes. Mol Cell Biol. 2009 Apr; 29(8):2193-204. PMID: 19188439.
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    46. Bejar R, Yasuda R, Krugers H, Hood K, Mayford M. Transgenic calmodulin-dependent protein kinase II activation: dose-dependent effects on synaptic plasticity, learning, and memory. J Neurosci. 2002 Jul 01; 22(13):5719-26. PMID: 12097524.
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    47. Moulton SL, Lynch FP, Cornish JD, Bejar RF, Simko AJ, Krous HF. Carotid artery reconstruction following neonatal extracorporeal membrane oxygenation. J Pediatr Surg. 1991 Jul; 26(7):794-9. PMID: 1895187.
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    48. Chamberlain MC, Press GA, Bejar RF. Neonatal schizencephaly: comparison of brain imaging. Pediatr Neurol. 1990 Nov-Dec; 6(6):382-7. PMID: 2127354.
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    49. Bejar RL, Smith GF, Park S, Spellacy WN, Wolfson SL, Nyhan WL. Cerebral gigantism: concentrations of amino acids in plasma and muscle. J Pediatr. 1970 Jan; 76(1):105-11. PMID: 4312004.
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