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    Rafael Bejar

    TitleAssistant Professor In Residence
    SchoolUniversity of California, San Diego
    Address9500 Gilman Drive #0820
    CA La Jolla 92093
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      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

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      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. Nazha A, Bejar R. Molecular Data and the IPSS-R: How Mutational Burden Can Affect Prognostication in MDS. Curr Hematol Malig Rep. 2017 Aug 26. PMID: 28844082.
        View in: PubMed
      2. Bejar R. Implications of molecular genetic diversity in myelodysplastic syndromes. Curr Opin Hematol. 2017 Mar; 24(2):73-78. PMID: 27875374.
        View in: PubMed
      3. 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 Jan; 15(1):60-87. PMID: 28040720.
        View in: PubMed
      4. Bejar R, Greenberg PL. The Impact of Somatic and Germline Mutations in Myelodysplastic Syndromes and Related Disorders. J Natl Compr Canc Netw. 2017 Jan; 15(1):131-135. PMID: 28040723.
        View in: PubMed
      5. 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
      6. 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 Jan; 52:1-7. PMID: 27855285.
        View in: PubMed
      7. 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 Aug 19; 16:652. PMID: 27538433; PMCID: PMC4991094.
      8. 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 Oct; 22(10):1535-49. PMID: 27492256.
        View in: PubMed
      9. Bejar R. Splicing Factor Mutations in Cancer. Adv Exp Med Biol. 2016; 907:215-28. PMID: 27256388.
        View in: PubMed
      10. 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
      11. 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; PMCID: PMC4653764.
      12. Bejar R. Myelodysplastic Syndromes Diagnosis: What Is the Role of Molecular Testing? Curr Hematol Malig Rep. 2015 Sep; 10(3):282-91. PMID: 26126599; PMCID: PMC4553153.
      13. 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; PMCID: PMC4624443.
      14. 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; PMCID: PMC4696005.
      15. 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; PMCID: PMC4396476.
      16. 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; PMCID: PMC4199102.
      17. Bejar R, Steensma DP. Recent developments in myelodysplastic syndromes. Blood. 2014 Oct 30; 124(18):2793-803. PMID: 25237199.
        View in: PubMed
      18. 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; PMCID: PMC4208285.
      19. 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; PMCID: PMC4207878.
      20. Bejar R. Clinical and genetic predictors of prognosis in myelodysplastic syndromes. Haematologica. 2014 Jun; 99(6):956-64. PMID: 24881041; PMCID: PMC4040892.
      21. Adema V, Bejar R. What lies beyond del(5q) in myelodysplastic syndrome? Haematologica. 2013 Dec; 98(12):1819-21. PMID: 24323981; PMCID: PMC3856955.
      22. 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
      23. 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
      24. Bejar R. Prognostic models in myelodysplastic syndromes. Hematology Am Soc Hematol Educ Program. 2013; 2013:504-10. PMID: 24319225.
        View in: PubMed
      25. 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; PMCID: PMC3438234.
      26. 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; PMCID: PMC3159042.
      27. 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; PMCID: PMC3969457.
      28. Bejar R, Ebert BL. The genetic basis of myelodysplastic syndromes. Hematol Oncol Clin North Am. 2010 Apr; 24(2):295-315. PMID: 20359627.
        View in: PubMed
      29. 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; PMCID: PMC2663304.
      30. 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.
        View in: PubMed
      31. Moulton SL, Lynch FP, Cornish JD, Bejar R, Simko AJ, Krous HF. Carotid artery reconstruction following neonatal extracorporeal membrane oxygenation. J Pediatr Surg. 1991 Jul; 26(7):794-9. PMID: 1895187.
        View in: PubMed
      32. Chamberlain MC, Press GA, Bejar R. Neonatal schizencephaly: comparison of brain imaging. Pediatr Neurol. 1990 Nov-Dec; 6(6):382-7. PMID: 2127354.
        View in: PubMed
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