Riccardo Dalla-Favera, MD

Profile Headshot

Overview

Academic Appointments

  • Percy and Joanne Uris Professor of Clinical Medicine
  • Professor of Pathology & Cell Biology
  • Professor of Microbiology and Immunology (in the Institute for Cancer Genetis and the Herbert Irving Comprehensive Cancer Center)

Administrative Titles

  • Director, Institute for Cancer Genetics

The general goal of this laboratory is to elucidate the pathogenesis of cancers derived from B lymphocytes, known as B cell lymphomas. These tumors originate from the malignant transformation of germinal center B cells, via acquisition of genomic lesions involving oncogenes and tumor suppressor genes. We wish to identify these lesions, determine the mechanism by which they occur and elucidate the contribution of each lesion to tumor development using genetically modified mouse models. These studies are also aimed at identifying targets for therapeutic intervention. Specific lines of investigation include:

1) Integrate genome-wide genomic and transcriptomic analyses to identify the genetic lesions involved in the development of Diffuse Large B Cell Lymphoma (DLBCL) and Chronic Lymphocytic Leukemia (CLL), the two most common forms of B cell malignancies.

2) Elucidate the physiologic role of the genes altered in DLBCL and CLL by identifying their function in germinal center development through the combination of biochemical and functional assays as well as genetically engineered mice with specific gene deletion in germinal center B cells.

3) Identify the pathologic role of DLBCL- and CLL-associated genetic lesions by recapitulating them in the germinal center of mice.

4) Test novel therapeutic approaches for their ability to target newly discovered genetic lesions and cellular pathways altered in tumors.

Email: rd10@cumc.columbia.edu

Languages

  • Italian

Credentials & Experience

Education & Training

  • MD, 1976 University of Milan

Honors & Awards

2007- Dameshek Award for Outstanding Contributions to Hematology, American Society of Hematology

2010- Elected Member, National Academy of Medicine

2012- Alfred G. Knudson Award for Pioneering Contributions to Cancer Genetics, National Cancer Institute

2015- Elected Member, National Academy of Sciences

2017- AACR G.H.A Clowes Memorial Award in Cancer Research, American Association for Cancer Research (AACR)

2017- Leopold Griffuel Award, Fondation ARC pour la Recherche sur Cancer, Villejuif, France

2017_ Elected Fellow of the Academy of the American Association for Cancer Research (AACR)

Research

Molecular genetics of cancer; molecular pathogenesis of lymphoma and leukemia; genetic control in lymphoid tissue development.

The general goal of this laboratory is to elucidate the pathogenesis of cancers derived from B lymphocytes, known as B cell lymphomas. These tumors originate from the malignant transformation of germinal center B cells, via acquisition of genomic lesions involving oncogenes and tumor suppressor genes. We wish to identify these lesions, determine the mechanism by which they occur and elucidate the contribution of each lesion to tumor development using genetically modified mouse models. These studies are also aimed at identifying targets for therapeutic intervention. Specific lines of investigation include: 1) Integrate genome-wide genomic and transcriptomic analyses to identify the genetic lesions involved in the development of Diffuse Large B Cell Lymphoma (DLBCL) and Chronic Lymphocytic Leukemia (CLL), the two most common forms of B cell malignancies. 2) Elucidate the physiologic role of the genes altered in DLBCL and CLL by identifying their function in germinal center development through the combination of biochemical and functional assays as well as genetically engineered mice with specific gene deletion in germinal center B cells. 3) Identify the pathologic role of DLBCL- and CLL-associated genetic lesions by recapitulating them in the germinal center of mice. 4) Test novel therapeutic approaches for their ability to target newly discovered genetic lesions and cellular pathways altered in tumors. 

Grants

CORE B

1P01CA174653-01A1

Project Dates: Apr 1 2014 to Mar 31 2019

FROM PATHOGENESIS TO NEW THERAPEUTIC TARGETS IN DIFFUSE LARGE B CELL LYMPHOMA

1R35CA210105-01

Project Dates: Aug 4 2016 to Jul 31 2023

MOLECULAR PATHOGENESIS OF B-CELL LYMPHOMA

FARC CU17-1853

Project Dates: Jun 1 2017 to May 31 2022

MSK SPORE IN LYMPHOMA (CAREER ENHANCEMENT PROGRAM)

MSKCC BD520441

Project Dates: Aug 30 2016 to Jul 31 2021

MSK SPORE IN LYMPHOMA-(PROJECT 4: TARGETING ACETYLTRANSFERASE GENE INACTIVATION IN DIFFUSE LARGE B CELL LYMPHOMA)

MSKCC BD520439

Project Dates: Aug 30 2016 to Jul 31 2021

THE ROLE OF NOTCH1 IN THE PATHOGENESIS OF CLL

1R01CA177319-05

Project Dates: Apr 1 2013 to Mar 31 2018             

CD58/CD1 TARGETED CANCER IMMUNE THERAPY

ABCC

Project Dates: Sep 15 2017 to Aug 14 2018  CORE B

FROM PATHOGENESIS TO NEW THERAPEUTIC TARGETS IN DIFFUSE LARGE B CELL LYMPHOMA (Federal Gov)

Aug 4 2016 - Jul 31 2023

MOLECULAR PATHOGENESIS OF B-CELL LYMPHOMA (Private)

Jun 1 2017 - May 31 2022

MSK SPORE IN LYMPHOMA (CAREER ENHANCEMENT PROGRAM) (Federal Gov)

Aug 30 2016 - Jul 31 2021

MSK SPORE IN LYMPHOMA-(PROJECT 4: TARGETING ACETYLTRANSFERASE GENE INACTIVATION IN DIFFUSE LARGE B CELL LYMPHOMA) (Federal Gov)

Aug 30 2016 - Jul 31 2021

CANCER CENTER SUPPORT GRANT (Federal Gov)

Jul 1 2014 - Jun 30 2019

ROLE OF MEF2B MUTATIONS IN LYMPHOMAGENESIS (Federal Gov)

May 15 2014 - Apr 30 2019

CORE B (Federal Gov)

Apr 1 2014 - Mar 31 2019

CD58/CD1 TARGETED CANCER IMMUNE THERAPY (Private)

Dec 6 2017 - Dec 5 2018

REPOSITIONING THERAPEUTIC PRINCIPLES FOR DIFFUSE LARGE B CELL LYMPHOMAS (Federal Gov)

Aug 1 2017 - Jul 31 2018

THE ROLE OF NOTCH1 IN THE PATHOGENESIS OF CLL (Federal Gov)

Apr 1 2013 - Mar 31 2018

ROLE OF ACETYLTRANSFERASE GENE INACTIVATION IN FOLLICULAR LYMPHOMA PATHOGENESIS (Federal Gov)

Apr 1 2012 - Mar 31 2017

IDENTIFYING NEW DRUGS FOR DLBCL TREATMENT (Private)

Jul 1 2013 - Jun 30 2016

ROLE OF MEF2B MUTATIONS IN LYMPHOMAGENESIS (Private)

Sep 1 2014 - Aug 31 2015

EXOME SEQUENCING OF HAIRY CELL LEUKEMIA AND CLASSICAL HODGKIN LYMPHOMA (Private)

Dec 1 2010 - Nov 30 2014

MOLECULAR DETERMINANTS OF FOLLICULAR LYMPHOMA TRANSFORMATION (Private)

Aug 1 2013 - Jul 31 2014

STEWART TRUST PILOT AWARDS FOR FY12-13 (YEAR 14) (Private)

Jul 1 2012 - Jun 30 2014

EXOME SEQUENCING IN RICHTER SYNDROME AND CHRONIC LYMPHOCYTIC LEUKEMIA (Private)

Jul 1 2010 - Jun 30 2014

SUBPROJECT FOR INSTITUTION # 08-8993 (Private)

Oct 1 2008 - Sep 30 2013

GENOMICS OF CHRONIC LYMPHOCYTIC LEUKEMIA (Private)

Aug 1 2011 - Jul 31 2013

WHOLE EXOME SEQUENCING OF PLASMABLASTIC LYMPHONA (PBL) PATIENTS (Private)

Jul 24 2012 - Jul 23 2013

AIDS ASSOCIATED LYMPHOPROLIFERATIVE DISORDERS (Federal Gov)

Jul 1 2007 - Jun 30 2013

AVON FOUNDATION BREAST CANCER PROGRAM AT THE HERBERT IRVING COMPREHENSIVE CANCER CENTER OF COLUMBIA UNIVERSITY MEDICAL C (Private)

Jan 1 2012 - Dec 31 2012

JJPRD CU11-3319 STUDY OF JNJ-26481585 IN CREBBP MUTATED DLBC L (Private)

Nov 10 2011 - Nov 9 2012

STEWART TRUST PILOT AWARDS (Private)

Jul 1 2008 - Jun 30 2012

STEWART TRUST PILOT AWARDS FOR 2008 - 10 (Private)

Jul 1 2008 - Jun 30 2012

STEWART TRUST PILOT AWARDS FOR 2009 (Private)

Jul 1 2008 - Jun 30 2012

ROLE OF BCL-6 IN GENERAL CENTER FORMATION AND LYMPHOMAGENES (Federal Gov)

Jul 1 2001 - Jun 30 2012

ROLE OF BCL-6 IN GERMINAL CENTER FORMATION AND LYMPHOMAGENESIS (Federal Gov)

Jul 1 2001 - Jun 30 2012

AVON FOUNDATION BREAST CANCER PROGRAM AT THE HERBERT IRVING COMPREHENSIVE CANCER CENTER OF COLUMBIA UNIVERSITY MEDICAL C (Private)

Jan 1 2011 - Dec 31 2011

IDENTIFICATION OF NOVEL MICRORNAS EXPRESSED IN B CELLS: ROLE IN NORMAL B CELL DEVELOPMENT AND LYMPHOMAGENESIS (Private)

Jul 1 2009 - Jun 30 2011

NOVEL ROLE OF C-MYC IN LYMPHOMAGENESIS (Private)

Jul 1 2008 - Jun 30 2011

AVON FOUNDATION BREAST CANCER PROGRAM AT THE HERBERT IRVING COMPREHENSIVE CANCER CENTER OF COLUMBIA UNIVERSITY MEDICAL C (Private)

Jan 1 2010 - Dec 31 2010

AVON FOUNDATION BREAST CANCER PROGRAM AT THE HERBERT IRVING COMPREHENSIVE CANCER CENTER OF COLUMBIA UNIVERSITY MEDICAL C (Private)

Jan 1 2009 - Dec 31 2010

ROLE OF MICRO RNAS (MIRS) INVOLVED IN HEMATOLYMPHOID DIFFERE NTION AND MALIGNANCY: IDENTIFICATION OF NOVEL MIRS EXPRESSSE (Private)

Feb 20 2009 - Dec 31 2009

MOLECULAR TARGETS IN LYMPHOMA COA (Private)

Oct 1 2003 - Sep 30 2009

ROLE OF NON-CODING RNAS LEU2, MIR15A AND MIR16-1 IN THE PATH OGENESIS OF CLL (Private)

Jul 1 2007 - Sep 30 2008

PILOT AWARDS FOR CANCER RESEARCH (Private)

Dec 1 1998 - Sep 30 2008

Selected Publications

   Dominguez-Sola, D., Ying, C.Y., Grandori, C., Ruggiero, L., Chen, B., Galloway, D.A., Gu, W., Gautier, J., Dalla-Favera. R.  Non-transcriptional control of DNA replication by c-myc.  Nature. 448(7152):445-51, 2007.

   Saito, M., Gao, J., Basso, K., Kitagawa , Y., Smith, PM., Pasqualucci, L., Dalla-Favera, R. A Signaling Pathway Mediating Downregulation of BCL6 in Germinal Center B Cells Is Blocked by BCL6 Gene Alterations in B Cell Lymphoma.  Cancer Cell. 12(3):280-92, 2007.

   Phan, RT., Saito, M., Kitagawa, Y., Means, A., Dalla-Favera, R.  Genotoxic stress regulates expression of the BCL6 proto-oncogene in germinal-center B cells.  Nat Immunol. 8(10):1132-1139, 2007.

   Pasqualucci, L., Bhagat, G., Jankovic, M., Compagno, M., Smith, P., Morse III, HC. Nussenzweig, MC., Dalla-Favera, R.  AID is required for germinal center derived lymphomagenesis. Nat Genet. 40(1):108-12, 2008.

   Basso, K., Sumazin, P., Morozov, P., Schneider, C., Maute, R.L., Kitagawa, Y., Mandelbaum,  J., Haddad, J. Jr., Chen, C.Z., Califano, A., Dalla-Favera, R. Identification of the human mature B cell miRNome. Immunity. 30(5):744-52, 2009

  Compagno, M., Lim, W.K., Grunn, A., Nandula, S.V., Brahmachary, M., Shen, Q., Bertoni, F., Ponzoni, M., Scandurra, M., Califano, A., Bhagat, G., Chadburn, A., Dalla-Favera, R. and Pasqualucci, L.  Mutations of multiple genes cause deregulation of the NF-kB pathway in diffuse large B-cell lymphoma. Nature. 459:717-21, 2009

Klein, U., Lia, M., Crespo, M., Siegel, R., Shen, Q., Mo, T., Ambesi-Impiombato, A., Califano, A., Migliazza, A., Bhagat, G., Dalla-Favera, R. The DLEU2/miR-15a/16-1 cluster controls B-cell proliferation and its deletion leads to chronic lymphocytic leukemia.  Cancer Cell. 17(1):28-40, 2010

Basso, K., Saito, M. Sumazin, P., Margolin, A.A., Wang, K., Lim, W. K., Kitagawa, Y., Schneider, C., Alvarez, M.J., Califano, A., Dalla-Favera, R. Integrated biochemical and computational approach identifies BCL6 direct target genes controlling multiple pathways in normal germinal-center B cells. Blood. 115(5):975-984, 2010

Mandelbaum, J., Bhagat, G., Tang, H., Mo, T., Brahmachary, M., Shen, Q.,  Chadburn, A., Rajewsky, K., Tarakhovsky, A., Pasqualucci L., and Dalla-Favera, A. BLIMP1 is a tumor suppressor gene frequently disrupted in activated B-cell like diffuse large B cell lymphoma. Cancer Cell. 18(6):568-79, 2010.

Pasqualucci, L., Dominguez-Sola, D., Chiarenza, A.,  Fabbri, G., Grunn, A., Trifonov, V., Kasper, L.H., Lerach, S., Tang, H., Ma, J., Rossi, D., Chadburn, A., V., Murty, V.V., Mullighan, C.G., Gaidano, G., Rabadan, R., Brindle, P.K., Dalla-Favera, R. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature. 471: (7337)189-95, 2011

Pasqualucci, L. Trifonov, V., Fabbri, G., Ma, J., Rossi, D., Chiarenza, A., Wells,   V.A., Grunn, A., Messina, M., Elliot, O., Chan, J., Bhagat, G., Chadburn, A., Gaidano, G., Mullighan, C. G., Rabadan, R., and Dalla-Favera, R. Analysis of the Coding Genome of Diffuse Large B-Cell Lymphoma. Nat Genet. 43(9):830-7, 2011.

Challa-Malladi, M., Lieu, Y.K., Califano, O., Holmes, A., Bhagat, G., Dominguez-Sola, D., Murty, V.V., Pasqualucci, L., Dalla-Favera, R. Combined Genetic Inactivation of Beta2-Microglobulin and CD58 Reveals Frequent Escape from Immune Recognition in Diffuse Large B-cell Lymphoma. Cancer Cell. 13:20(6):728-40, 2011

Dominguez-Sola, D., Victora, G.D., Ying, C.Y., Phan, R.T., Saito, M., Nussenzweig, M.C., Dalla-Favera, R. The proto-oncogene MYC is required for selection in the germinal center and cyclic reentry. Nat Immunol. 13(11):1083-91, 2012

Ying, C.Y., Dominguez-Sola, D., Fabi, M., Lorenz, I.C., Hussein, S., Bansal, M., Califano, A., Pasqualucci, L., Basso, K., Dalla-Favera, R. MEF2B mutations lead to deregulated expression of the BCL6 oncogene in diffuse large B cell lymphoma.  Nat Immunol. 10:1084-92, 2013

Pasqualucci, L., Khiabanian, H., Fangazio, M., Vasishtha, M., Messina, M., Holmes, A.B., Ouillette, P., Trifonov, V., Rossi, D., Tabbò, F., Ponzoni, M., Chadburn, A., Murty, V.V., Bhagat, G., Gaidano, G., Inghirami, G., Malek, S.N., Rabadan, R., Dalla-Favera, R. Genetics of Follicular Lymphoma Transformation. Cell Rep. 16;6(1):130-40, 2014

Trimarchi, T., Bilal, E., Ntziachristos, P., Fabbri, G., Dalla-Favera, R., Tsirigos, A., Aifantis, I. Genome-wide Mapping and Characterization of Notch-Regulated Long Noncoding RNAs in Acute Leukemia. Cell. 158(3):593-606, 2014

Basso, K., Dalla-Favera, R. Germinal Centres and B cell lymphomagenesis. Nat Rev Immunol 15(3):172-84, 2015

Zhang, J., Dominguez-Sola, D., Hussein, S., Lee, J.E., Holmes, A.B., Bansal, M., Vlasevska, S., Mo, T., Tang, H., Basso, K., Ge, K., Dalla-Favera, R., Pasqualucci, L. Disruption of KMT2D perturbs germinal center B cell development and promotes lymphomagenesis. Nat Med. 21(10):1190-8, 2015

Dominguez-Sola, D., Kung, J., Holmes, A.B., Wells, V.A., Mo, T., Basso, K., Dalla-Favera, R. The FOXO1 Transcription Factor Instructs the Germinal Center Dark Zone Program. Immunity. 43(6):1064-74, 2015

Fabbri, G., Dalla-Favera, R. The molecular pathogenesis of chronic lymphocytic leukaemia. Nat Rev Cancer, 16(3):145-62, 2016

Zhang, J. Vlasevska, S., Wells, V.A., Nataraj, S., Holmes, A.B., Duval, R., Meyer, S.N., Mo, T., Basso, K., Brindle, P.K., Hussein, S., Dalla-Favera, R., Pasqualucci, L. The Crebb Acetyltransferase is a Haploinsufficient Tumor Suppressor in B Cell Lymphoma. Cancer Discov. 7(3):322-337, 2017

Fabbri, G., Holmes, A.B., Viganotti, M., Scuoppo, C., Belver, L., Herranz, D., Yan, X.J., Kieso, Y., Rossi, D., Gaidano, G., Chiorazzi, N., Ferrando, A.A., Dalla-Favera, R. Common nonmutational NOTCH1 activation in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 114(14):E2911-E2919, 2017