Research Groups

Dimitar Efremov

Molecular Hematology

Group Leader

Research Interests and Description
Group Members

Dimitar Efremov

International Centre for Genetic Engineering and Biotechnology
Padriciano 99
34149 Trieste, Italy

E-mail: efremovicgeb.org
Tel: +39-040-3757212
Fax: +39-040-226555

Education

Faculty of Medicine, University of St. Cyril and Methodius, Skopje, Macedonia, MD, 1986
Maastricht University, Maastricht, The Netherlands, PhD., 1994
Faculty of Medicine, Univ. St. Cyril and Methodius, Skopje, Macedonia, Specialist in Internal Medicine-Hematology, 1999

Career History

Since 2015, Staff Scientist and Head of the ICGEB Molecular Hematology Group, ICGEB Trieste, Italy
2004-2015, Staff Scientist and Head of the ICGEB Molecular Hematology Group at the Monterotondo Outstation, Rome, Italy
2001-2006, Associate Professor of Internal Medicine, Department of Hematology, Faculty of Medicine, Skopje, Macedonia
1998-2001, Assistant Professor, Department of Hematology, Faculty of Medicine, Skopje, Macedonia
1996-1998, Assistant Research Scientist, ICGEB, Trieste, Italy
1994-1996, Junior Scientist, ICGEB, Trieste, Italy
1993, International Research Fellow, Medical College of Georgia, Augusta, Ga, USA
1989-1992, Resident, Department of Hematology, Faculty of Medicine, Skopje, Macedonia
1988-1989, Research Associate, Research Center for New Technologies, Macedonian Academy of Sciences and Arts, Skopje, Macedonia
1987, International Research Fellow, Medical College of Georgia, Augusta, Ga, USA.

Scientific Activity

Dr. Efremov's primary research interest is chronic lymphocytic leukemia, particularly investigation of the cellular and molecular mechanisms governing the development and progression of the disease and development of novel targeted therapies. He has also made numerous contributions in other areas related to hematological and immunological disorders, including B-cell lymphoma, hemoglobinopathies, autoimmune blood disorders, allergy and bone marrow transplantation. He has authored or co-authored more than 100 articles in peer-reviewed international journals. He has received grants from various prestigious international and national funding bodies, including the Leukemia & Lymphoma Society and the Italian Association for Cancer Research. He is a member of the editorial boards of Haematologica, the American Journal of Blood Research, the Mediterranean Journal of Hematology and Infectious Diseases, EMJ Hematology and several other international scientific journals.

Other Activities

2015,Elected external member of Macedonian Academy of Sciences and Arts
2013, Received Italian national habilitation for Associate Professor of Hematology
2010, Elected Associate Professor of Molecular Biology, University of Nova Gorica, Slovenia
2000-2002, Member of National Committee for Registration of Pharmaceuticals in the Republic of Macedonia
1999-2002, Consultant physician for the European Union Delegation in Macedonia

Selected publications

D. Efremov on PubMed

Iacovelli S, Hug E, Bennardo S, Duehren-von Minden M, Gobessi S, Rinaldi A, Suljagic M, Bilbao D, Bolasco G, Eckl-Dorna J, Niederberger V, Autore F, Sica S, Laurenti L, Wang H, Cornall RJ, Clarke SH, Croce CM, Bertoni F, Jumaa H, Efremov DG. Two types of BCR interactions are positively selected during leukemia development in the Eμ-TCL1 transgenic mouse model of CLL. Blood. 2015;125(10):1578-1588.

Efremov DG, Gobessi S. Signal-dependent and signal-independent functions of the B-cell receptor in chronic lymphocytic leukemia. Haematologica. 2014;99(11):1645-6.

Woyach JA, Bojnik E, Ruppert AS, Stefanovski MR, Goettl VM, Smucker KA, Smith LL, Dubovsky JA, Towns WH, Macmurray J, Harrington BK, Davis ME, Gobessi S, Laurenti L, Chang BY, Buggy JJ, Efremov DG, Byrd JC, Johnson AJ. Bruton's tyrosine kinase (BTK) function is important to the development and expansion of chronic lymphocytic leukemia (CLL). Blood. 2014;123(8):1207-13

Rossi D, Spina V, Bomben R, Rasi S, Dal-Bo M, Bruscaggin A, Rossi FM, Monti S, Degan M, Ciardullo C, Serra R, Zucchetto A, Nomdedeu J, Bulian P, Grossi A, Zaja F, Pozzato G, Laurenti L, Efremov DG, Di-Raimondo F, Marasca R, Forconi F, Del-Poeta G, Gaidano G, Gattei V. Association between molecular lesions and specific B-cell receptor subsets in chronic lymphocytic leukemia. Blood. 2013; 121(24):4902-5.

Chiorazzi N, Efremov DG. CLL: A tale of one or two signals? Cell Res. 2013;23(2):182-5.

Efremov, D.G., Wiestner, A., Laurenti, L. 2012. Novel agents and emerging strategies for targeting the B-cell receptor pathway in CLL. Mediterr J Hematol Infect Dis, 4, e2012067, DOI 10.4084/MJHID.2012.067

Negro R, Gobessi S, Longo PG, He Y, Zhang ZY, Laurenti L, Efremov DG. Overexpression of the autoimmunity-associated phosphatase PTPN22 promotes survival of antigen-stimulated chronic lymphocytic leukemia cells by selectively activating the AKT pathway. Blood. 2012; 119(26):6278-87 PubMed Link

Bomben R, Gobessi S, Bo MD, Volinia S, Marconi D, Tissino E, Benedetti D, Zucchetto A, Rossi D, Gaidano G, Poeta GD, Laurenti L, Efremov DG, Gattei V. The miR-17~92 family regulates the response to toll-like receptor 9 triggering of CLL cells with unmutated IGHV genes. Leukemia. 2012; 26(7):1584-93 PubMed link

Careta FP, Gobessi S, Panepucci RA, Bojnik E, de Oliveira FM, Matos DM, Falcao RP, Laurenti L, Zago MA, Efremov DG. The Aurora A and B kinases are upregulated in bone marrow-derived chronic lymphocytic leukemia cells and represent potential therapeutic targets. Haematologica. 2012; 97(8):1246-54 PubMed link

Efremov DG, Laurenti L. The Syk kinase as a therapeutic target in leukemia and lymphoma. Expert Opin Investig Drugs. 2011; 20:623-36.

Suljagic M, Laurenti L, Tarnani M, Alam M, Malek SN, Efremov DG. Reduced expression of the tumor suppressor PHLPP1 enhances the antiapoptotic B-cell receptor signal in chronic lymphocytic leukemia B cells. Leukemia. 2010; 24:2063-71.

Suljagic M, Longo PG, Bennardo S, Perlas E, Leone G, Laurenti L, Efremov DG. The Syk inhibitor fostamatinib disodium (R788) inhibits tumor growth in the E{micro}-TCL1 transgenic mouse model of CLL by blocking antigen-dependent B cell receptor signaling. Blood. 2010; 116:4894-905.

Carsetti L, Laurenti L, Gobessi S, Longo PG, Leone G, Efremov DG. Phosphorylation of the activation loop tyrosines is required for sustained Syk signaling and growth factor-independent B-cell proliferation. Cell Signal. 2009; 21:1187-94

Gobessi S, Laurenti L, Longo PG, Carsetti L, Berno V, Sica S, Leone G, Efremov DG. Inhibition of constitutive and BCR-induced Syk activation downregulates Mcl-1 and induces apoptosis in chronic lymphocytic leukemia B-cells. Leukemia. 2009; 23:686-97.

Longo P, Laurenti L, Gobessi S, Sica S, Leone G, Efremov DG. The Akt/Mcl-1 pathway plays a prominent role in mediating antiapoptotic signals downstream of the B-cell receptor in chronic lymphocytic leukemia B cells. Blood. 2008; 111:846-55.

Efremov DG, Gobessi S, Longo PG. Signaling pathways activated by antigen-receptor engagement in chronic lymphocytic leukemia B-cells. Autoimmun Rev. 2007; 7:102-8.

Deaglio S, Vaisitti T, Aydin S, Bergui L, D'Arena G, Bonello L, Omede P, Scatolini M, Jaksic O, Chiorino G, Efremov D, Malavasi F. CD38 and ZAP-70 are functionally linked and mark CLL cells with high migratory potential. Blood. 2007; 110:4012-21. 

Bomben R, Dal-Bo M, Capello D, Benedetti D, Marconi D, Zucchetto A, Forconi F, Maffei R, Ghia EM, Laurenti L, Bulian P, Del Principe MI, Palermo G, Thorsélius M, Degan M, Campanini R, Guarini A, Del Poeta G, Rosenquist R, Efremov DG, Marasca R, Foà R, Gaidano G, Gattei V. Comprehensive characterization of IGHV3-21-expressing B-cell chronic lymphocytic leukemia: an Italian multicenter study. Blood. 2007; 109, 2989-98.

Gobessi S, Laurenti L, Longo PG, Sica S, Leone G, Efremov DG. ZAP-70 enhances B-cell receptor signaling despite absent or inefficient tyrosine kinase activation in chronic lymphocytic leukemia and lymphoma B-cells. Blood. 2007; 109:2032-9.

Longo P, Laurenti L, Gobessi S, Petlickovski A, Pelosi M, Chiusolo P, Sica S, Leone G, Efremov DG. The Akt signaling pathway determines the different proliferative capacity of chronic lymphocytic leukemia B-cells from patients with progressive and stable disease. Leukemia. 2007, 21:110-120.

Yan XJ, Albesiano E, Zanesi N, Yancopoulos S, Sawyer A, Romano E, Petlickovski A, Efremov DG, Croce CM, Chiorazzi N. B cell receptors in TCL1 transgenic mice resemble those of aggressive, treatment-resistant human chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2006; 103:11713-8.

Laurenti L, Petlickovski A, Rumi C, Gobessi S, Piccioni P, Tarnani M, Puggioni P, Marrietti S, Sica S, Leone G, Efremov DG. Comparison of ZAP-70/Syk mRNA levels with immunoglobulin heavy-chain gene mutation status and disease progression in chronic lymphocytic leukemia. Haematologica. 2005; 90:1533-40.

Petlickovski A, Laurenti L, Li X, Marietti S, Chiusolo P, Sica S, Leone G, Efremov DG.  Sustained signaling through the B-cell receptor induces Mcl-1 and promotes survival of chronic lymphocytic leukemia B-cells. Blood. 2005; 105:4820-7.

Messmer BT, Albesiano E, Efremov DG, Ghiotto F, Allen SL, Kolitz J, Foa R, Damle RN, Fais F, Messmer D, Rai KR, Ferrarini M, Chiorazzi N. Multiple distinct sets of stereotyped antigen receptors indicate a role for antigen in promoting chronic lymphocytic leukemia. J. Exp. Med. 2004; 200, 519-525.

Efremov DG, Georgievski B, Cevreska L, Pivkova A, Panovska I. Lamivudine treatment for acute hepatitis B virus infection during allogeneic peripheral blood stem cell transplantation. Bone Marrow Transplant. 2003; 31, 515-6.

Pavkovic M, Georgievski B, Cevreska L, Spiroski M, Efremov DG. CTLA-4 exon 1 polymorphism in patients with autoimmune blood disorders. Am. J. Hematol. 2003; 72, 147-9.

Benvenuti F, Burrone OR, Efremov DG. Anti-idiotypic DNA vaccines for lymphoma immunotherapy require the presence of both variable region genes for complete tumor protection. Gene Ther. 2000; 7: 605-611.

Panovska I, Georgievski B, Stojanovic A, Cevreska L, Efremov DG. Low Prevalence of Chronic Hepatitis C Virus Infection in B-cell Non-Hodgkin's Lymphoma Patients from a Population with a High Prevalence of Healthy HCV Carriers. Br. J. Haematol. 2000; 109: 249-250.

Pozzato G, Burrone O, Baba K, Matsumoto M, Hijiiata M, Ota Y, Mazzoran L, Baracetti S, Zorat F, Mishiro S, Efremov DG. Ethnic difference in the prevalence of monoclonal B-cell proliferations in patients affected by hepatitis C virus chronic liver disease. J. Hepatol. 1999; 30: 990-994.

Ivanovski M, Silvestri F, Pozzato G, Anand S, Mazzaro C, Burrone OR, Efremov DG. Somatic hypermutation, clonal diversity and preferential expression of the VH 51p1/VL Humkv325 Ig gene combination in HCV-associated lymphoplasmacytoid lymphoma. Blood. 1998; 91: 2433-2442.

Efremov DG, Ivanovski M, Burrone OR. The Pathologic Significance of the Immunoglobulin Expressed by Chronic Lymphocytic Leukemia B-cells in the Development of Autoimmune Hemolytic Anemia. Leuk. Lymphoma. 1998; 28: 285-293.

Efremov DG, Ivanovski M, Batista FD, Pozzato G, Burrone OR. IgM-producing chronic lymphocytic leukemia cells undergo Ig-isotype switching without acquiring somatic mutations. J. Clin. Invest. 1996; 98: 290-298.

Efremov DG, Ivanovski M, Siljanovski N, Pozzato G, Cevreska L, Fais F, Chiorazzi N, Batista FD, Burrone OR. Restricted Immunoglobulin VH region repertoire in chronic lymphocytic leukemia patients with autoimmune hemolytic anemia. Blood. 1996; 87: 3869-3876.

Efremov DG, Dimovski AJ, Huisman TH. The -158 (C->T) promoter mutation is responsible for the increased transcription of the 3' gamma-globin gene in the Atlanta Type of Hereditary Persistence of Fetal Hemoglobin. Blood. 1994; 83: 3350-3355

Efremov DG, Dimovski AJ, Sukarova E, Schiliro G, Zisovski N, Efremov GD, Burrone OR, Huisman TH. gamma-mRNA and Hb F levels in beta+ thalassemia. Br. J. Haematol. 1994; 88: 311-317.

Efremov DG, Dimovski AJ, Baysal E, Ye Z, Adekile AD, Ribeiro ML, Schiliro G, Altay C, Gurgey A, Efremov GD, Huisman TH. Possible factors influencing the haemoglobin and foetal haemoglobin levels in patients with beta-thalassemia due to a homozygosity for the IVS-I-6 (T->C) mutation. Br. J. Haematol. 1994; 86: 824-830.

Efremov DG, Batista FD, Burrone OR. Molecular analysis of IgE heavy chain transcripts expressed in vivo by peripheral blood lymphocytes from normal and atopic individuals. J. Immunol. 1993; 151: 2195-2207.

Efremov DG, Efremov GD, Zisovski N, Stojanovski N, Kutlar F, Diaz-Chico JC, Kutlar A, Yang KG, Stoming TA, Huisman THJ. Variation in clinical severity among patients with Hb Lepore Boston-beta-thalassemia is related to the type of beta-thalassemia. Br. J. Haematol. 1988; 68: 351-355.

Diaz-Chico JC, Yang KG, Stoming TA, Efremov DG, Kutlar A, Kutlar F, Aksoy M, Altay C, Gurgey A, Kilinc Y, Huisman THJ. Mild and severe beta-thalassemia among homozygotes from Turkey: Identification of the types by hybridization of amplified DNA with synthetic probes. Blood. 1988; 71: 248-251.

 

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