Laura Pasqualucci, MD

  • Professor of Pathology & Cell Biology (in the Institute for Cancer Genetics) at CUMC
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Overview

Dr. Laura Pasqualucci is a Professor of Pathology & Cell Biology in the Institute for Cancer Genetics at Columbia University Irving Medical Center. She earned her M.D. Summa Cum Laude from the University of Perugia School of Medicine, where she also completed her residency in Hematology. Dr. Pasqualucci is a member of the Interurban Clinical Club, the American Association for Cancer Research, and the American Society of Hematology.

Dr. Pasqualucci’s research focuses on the molecular pathogenesis of B cell malignancies, particularly diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL). Her laboratory employs multi-omics approaches, biochemical assays, and genetically engineered mouse models to uncover genetic alterations driving these cancers. A major focus of her work includes studying the tumor-suppressive roles of histone/chromatin modifiers like KMT2D and CREBBP, which her research has identified as recurrent mutational targets in FL/DLBCL. Additionally, she investigates the impact of non-coding mutations in super-enhancer regions on lymphoma pathogenesis. Dr. Pasqualucci’s research is aimed at developing novel biomarkers and therapeutic strategies for B-cell lymphomas.

Academic Appointments

  • Professor of Pathology & Cell Biology (in the Institute for Cancer Genetics) at CUMC

Credentials & Experience

Committees, Societies, Councils

  • American Society of Hematology: Committee on Scientific Affairs
  • Lymphoma Research Foundation: Scientific Advisory Board
  • Lymphoma Research Foundation: Grant Oversight Committee
  • American Society of Hematology: Member
  • American Association of Cancer Research: Member

Research

Laura Pasqualucci’s research interests focus on the molecular pathogenesis of B cell malignancies, with emphasis on its most common types, diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL). The laboratory takes advantage of integrated multi-omics approaches, biochemical assays, and genetically-engineered mouse models to identify and functionally characterize the genetic alterations associated with these cancers, and to understand the role of the affected genes in the physiologic germinal center (GC) reaction, a specialized microenvironment from which most B cell lymphomas arise. A major area of investigation focuses on the methyltransferase KMT2D and the acetyltransferase CREBBP, two histone/chromatin modifiers that we discovered as highly recurrent mutational targets and early events in the evolutionary history of FL/DLBCL. These genes have emerged as central players in many different cancers, and we have documented they act as tumor suppressors genes, the loss of which contributes to lymphomagenesis by remodeling the epigenome of the GC. This information is currently being exploited for the development of novel biomarkers and rational treatment options in these diseases.

Selected Publications

  • Bal E, Kumar R, Hadigol M, Holmes AB, Hilton LK, Loh JW, Dreval K, Wong JCH, Vlasevska S, Corinaldesi C, Soni RK, Basso K, Morin RD, Khiabanian H, Pasqualucci L, Dalla-Favera R.. Super-enhancer hypermutation alters oncogene expression in B cell lymphoma. Nature 2022 PMID: 35794478, DOI: 10.1038/s41586-022-04906-8.
  • Fangazio M, Ladewig E, Gomez K, Garcia-Ibanez L, Kumar R, Teruya-Feldstein J, Rossi D, Filip I, Pan-Hammarström Q, Inghirami G, Boldorini R, Ott G, Staiger AM, Chapuy B, Gaidano G, Bhagat G, Basso K, Rabadan R, Pasqualucci L, Dalla-Favera R.. Genetic mechanisms of HLA-I loss and immune escape in diffuse large B cell lymphoma. Proc Natl Acad Sci U S A. 2021 PMID: 34050029, DOI: 10.1073/pnas.2104504118
  • Liu Z, Filip I, Gomez K, Engelbrecht D, Meer S, Lalloo PN, Patel P, Perner Y, Zhao J, Wang J, Pasqualucci L, Rabadan R, Willem P. Genomic characterization of HIV-associated plasmablastic lymphoma identifies pervasive mutations in the JAK-STAT pathway. Blood Cancer Discov. 2020. PMID: 33225311, DOI: 10.1158/2643-3249.bcd-20-0051
  • Meyer SN, Scuoppo C, Vlasevska S, Bal E, Holmes AB, Holloman M, Garcia-Ibanez L, Nataraj S, Duval R, Vantrimpont T, Basso K, Brooks N, Dalla-Favera R, Pasqualucci L. Unique and Shared Epigenetic Programs of the CREBBP and EP300 Acetyltransferases in Germinal Center B Cells Reveal Targetable Dependencies in Lymphoma. Immunity. 2019. PMID: 31519498, DOI: 10.1016/j.immuni.2019.08.006
  • Pasqualucci L. Molecular pathogenesis of germinal center-derived B cell lymphomas. Immunol Rev. 2019. PMID: 30874347, DOI: 10.1111/imr.12745
  • Zhang J, Vlasevska S, Wells VA, Nataraj S, Holmes AB, Duval R, Meyer SN, Mo T, Basso K, Brindle PK, Hussein S, Dalla-Favera R, Pasqualucci L. The CREBBP Acetyltransferase Is a Haploinsufficient Tumor Suppressor in B-cell Lymphoma. Cancer Discov. 2017. PMID: 28069569, DOI: 10.1158/2159-8290.CD-16-1417
  • Zhang J, Dominguez-Sola D, Hussein S, Lee JE, Holmes AB, 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. 2015. PMID: 26366712, DOI: 10.1038/nm.3940
  • Pasqualucci L, Khiabanian H, Fangazio M, Vasishtha M, Messina M, Holmes AB, Ouillette P, Trifonov V, Rossi D, Tabbò F, Ponzoni M, Chadburn A, Murty VV, Bhagat G, Gaidano G, Inghirami G, Malek SN, Rabadan R, Dalla-Favera R. Genetics of follicular lymphoma transformation. Cell Rep. 2014. PMID: 24388756, DOI: 10.1016/j.celrep.2013.12.027
  • Challa-Malladi M, Lieu YK, Califano O, Holmes AB, Bhagat G, Murty VV, Dominguez-Sola D, Pasqualucci L, Dalla-Favera R. Combined genetic inactivation of β2-Microglobulin and CD58 reveals frequent escape from immune recognition in diffuse large B cell lymphoma. Cancer Cell. 2011. PMID: 22137796, DOI: 10.1016/j.ccr.2011.11.006
  • Pasqualucci L, Trifonov V, Fabbri G, Ma J, Rossi D, Chiarenza A, Wells VA, Grunn A, Messina M, Elliot O, Chan J, Bhagat G, Chadburn A, Gaidano G, Mullighan CG, Rabadan R, Dalla-Favera R. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat Genet. 2011. PMID: 21804550, DOI: 10.1038/ng.892
  • Fabbri G, Rasi S, Rossi D, Trifonov V, Khiabanian H, Ma J, Grunn A, Fangazio M, Capello D, Monti S, Cresta S, Gargiulo E, Forconi F, Guarini A, Arcaini L, Paulli M, Laurenti L, Larocca LM, Marasca R, Gattei V, Oscier D, Bertoni F, Mullighan CG, Foá R, Pasqualucci L, Rabadan R, Dalla-Favera R, Gaidano G. Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation. J Exp Med. 2011. PMID: 21670202, DOI: 10.1084/jem.20110921
  • Pasqualucci L, Dominguez-Sola D, Chiarenza A, Fabbri G, Grunn A, Trifonov V, Kasper LH, Lerach S, Tang H, Ma J, Rossi D, Chadburn A, Murty VV, Mullighan CG, Gaidano G, Rabadan R, Brindle PK, Dalla-Favera R. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature. 2011. PMID: 21390126, DOI: 10.1038/nature09730
  • Mandelbaum J, Bhagat G, Tang H, Mo T, Brahmachary M, Shen Q, Chadburn A, Rajewsky K, Tarakhovsky A, Pasqualucci L, Dalla-Favera R. BLIMP1 is a tumor suppressor gene frequently disrupted in activated B cell-like diffuse large B cell lymphoma. Cancer Cell. 2010. PMID: 21156281, DOI: 10.1016/j.ccr.2010.10.030
  • Compagno M, Lim WK, Grunn A, Nandula SV, Brahmachary M, Shen Q, Bertoni F, Ponzoni M, Scandurra M, Califano A, Bhagat G, Chadburn A, Dalla-Favera R, Pasqualucci L. Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma. Nature. 2009. PMID: 19412164, DOI: 10.1038/nature07968
  • Pasqualucci L, Bhagat G, Jankovic M, Compagno M, Smith P, Muramatsu M, Honjo T, Morse HC, Nussenzweig MC, Dalla-Favera R. AID is required for germinal center-derived lymphomagenesis. Nat Genet. 2008. PMID: 18066064, DOI: 10.1038/ng.2007.35
  • Cattoretti G, Pasqualucci L, Ballon G, Tam W, Nandula SV, Shen Q, Mo T, Murty VV, Dalla-Favera R. Deregulated BCL6 expression recapitulates the pathogenesis of human diffuse large B cell lymphomas in mice. Cancer Cell. 2005. PMID: 15894265, DOI: 10.1016/j.ccr.2005.03.037
  • Pasqualucci L, Neumeister P, Goossens T, Nanjangud G, Chaganti RS, Küppers R, Dalla-Favera R. Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature. 2001. PMID: 11460166, DOI: 10.1038/35085588

For a complete list of publications, please visit PubMed.gov