Laura Pasqualucci, MD
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.
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.