Laura Pasqualucci, MD

Profile Headshot

Overview

Academic Appointments

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

Dr. 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 genomic profiling approaches and genetically modified mouse models to identify and functionally characterize the genetic lesions that are associated with these cancers, as a tool to better understand the mechanisms that are responsible for the initiation and maintenance of the tumor cell. The ultimate goal is to develop improved biomarkers and more effective treatment options for lymphoid malignancies.

Over the past decade, Dr Pasqualucci's work has led to the discovery of multiple genes that are recurrently disrupted by genetic lesions in lymphoma and play a critical role in both normal and transformed germinal center B cells. More recently, her group uncovered highly frequent mutations in genes that encode for epigenetic modifiers, including the methyltransfersase KMT2D and the acetyltransferases CREBBP and p300. These genes have emerged as central players in many different cancers, and were documented as tumor suppressors in lymphoma. This information is currently being exploited for the development of improved targeted therapeutic approaches in these diseases.  

Email: lp171@cumc.columbia.edu

Languages

  • Italian
  • Spanish

Credentials & Experience

Education & Training

  • MD, 1991 Medicine, University of Perugia (Italy)
  • Residency: 1995 University of Perugia (Italy)
  • Fellowship: Columbia University - NY

Research

Research Interests

  • Mature B cell malignancies, emphasis on diffuse large B cell lymphoma and follicular lymphoma

Grants

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

Aug 4 2016 - Jul 31 2023

ROLE OF KMT2D GENE INACTIVATION IN B CELL NON-HODGKIN LYMPHOMA (Federal Gov)

Jul 3 2018 - Jun 30 2023

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

Aug 30 2016 - Jul 31 2021

TARGETING EPIGENETIC ADDICTIONS IN KMT2D MUTATED B CELL LYMPHOMAS (Private)

Jul 1 2018 - Jun 30 2021

IMMUNE REGULATION OF TRIPLE NEGATIVE BREAST CANCER METASTASIS (Private)

Jul 18 2017 - Jul 17 2020

ROLE OF TUMOR-INFILTRATING B CELLS IN BREAST CANCER METASTASIS (Federal Gov)

Mar 1 2017 - Feb 28 2020

IDENTIFYING TARGETABLE GENETIC DEPENDENCIES IN CREBBP-DEFICIENT B CELL LYMPHOMA (Private)

Dec 1 2017 - Nov 30 2018

GENETIC DETERMINANTS OF PRIMARY CHEMO-RESISTANCE IN DIFFUSE LARGE B CELL LYMPHOMA (Federal Gov)

Aug 1 2017 - Jul 31 2018

THE CODING GENOME OF HIV ASSOCIAED PLASMABLASTIC LYMPHOMAS IN SOUTH AFRICA (Federal Gov)

May 1 2015 - Apr 30 2017

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

Apr 1 2012 - Mar 31 2017

INACTIVATING MUTATIONS OF THE MLL2 GENE IN MATURE B-CELL LYMPHOMAS (Private)

Mar 1 2015 - Feb 29 2016

ROLE OF METHYLTRANSFERASE GENE INACTIVATION IN DIFFUSE LARGE B CELL LYMPHOMA (Private)

Aug 1 2012 - Jul 31 2014

SUBPROJECT FOR INSTITUTION # 08-8993 (Private)

Oct 1 2008 - Sep 30 2013

AIDS ASSOCIATED LYMPHOPROLIFERATIVE DISORDERS (Federal Gov)

Jul 1 2007 - Jun 30 2013

SYSTEMS BIOLOGY OF TUMOR PROGRESSION AND DRUG-RESISTANCE (Federal Gov)

Sep 30 2009 - Aug 31 2012

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

Jul 1 2001 - Jun 30 2012

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

Jul 1 2009 - Jun 30 2011

Selected Publications

Zhang J, Vlasevska S, Wells VA, Nataraj S, Antony 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 Discovery, 2017; Jan 9. pii: CD-16-1417. doi: 10.1158/2159-8290 [Epub ahead of print].

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. Nature Medicine 2015; 21(10):1190-8. PMID: 26366712

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 Reports, 2014; 6(1): 130-140. PMCID: PMC4100800. (*corresponding authors)

Ying CY, Dominguez-Sola D, Fabi M, Lorenz IC, 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. Nature Immunology, 2013; 14(10):1084-1092.

Pasqualucci L*, Dominguez-Sola D, Chiarenza A, Fabbri A, 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 and Dalla-Favera R*. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature, 2011; 471(7337):189-195. (*corresponding authors)

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. Nature Genetics, 2011; 43:830-837, 2011. (*corresponding authors)

Challa-Malladi M, Lieu YK, Califano O, Holmes A, Bhagat G, Murty VV, Dominguez-Sola D, 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, 2011; 20(6): 728-740. (*equal contribution)

Mandelbaum J, Bhagat G, Tang H, Mo T, Grunn A, 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; 18(6):568-579. (*equal contribution).

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 in multiple genes cause deregulation of the NF-B pathway in diffuse large B-cell lymphoma. Nature, 2009; 459(7247):717-721.

Pasqualucci L*, Bhagat G, Jankovic M, Compagno M, Smith P, Muramatsu M, Honjo T, Morse HC 3rd, Nussenzweig MC, Dalla-Favera R*. AID is required for germinal center-derived lymphomagenesis. Nature Genetics, 2008; 40:108-112. (*corresponding authors).

Pasqualucci L, Neumeister P, Goossens T, Nanjangud G, Chaganti RSK, Küppers R, Dalla-Favera R. Hypermutation of multiple proto-oncogenes in B-cell Diffuse Large Cell Lymphomas Nature, 2001; 412: 341-346.