- ASSISTANT PROFESSOR Oncological Sciences
- ASSISTANT PROFESSOR Pathology
Oncogenes and Early B cell Lymphomagenesis
Invisible to the human eye, cancer initiation is believed to shape the molecular and cellular landscape of all cancers. Although we have been able to probe these pre-malignant stages in a handful of tumor types, our knowledge remains exceptionally limited for other malignancies like B-cell lymphomas.
B cell lymphomas occur both in adult and children, being one of the most common cancers in the latter group. Notably, an important fraction of lymphomas rely on the activation of oncogenes through particular genetic rearrangements (e.g. translocations). These genetic events are known to drive lymphomagenesis in animal models, and constitute a useful system to study the basic mechanisms of cancer initiation and progression.
Most human B-cell lymphomas arise from B-lymphocytes (B cells) recruited to transient microanatomic structures known as Germinal Centers. Germinal centers are highly organized and dynamic compartments where B cells are trained and selected for their ability to efficiently recognize antigens, a process that is essential to sustain efficient immune responses. However, the molecular and cellular events driving the germinal center also impose a high risk for cellular transformation and lymphomagenesis.
Our laboratory is particularly interested in understanding the early steps of B cell lymphomagenesis, and in deciphering how the tissue and cellular contexts affect how oncogenes drive lymphoma initiation and shape the genetic landscape of lymphoma cells, with a particular interest in B-cell lymphomas driven by deregulation of the c-Myc protooncogene. To address these questions we use a multiplicity of in vitro and in vivo methodologies that combine strategies borrowed from both the cancer biology and immunology fields. Using this approach we are refining our knowledge on the cellular origin of B-cell lymphomas and the basic mechanisms of cancer initiation.
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 oncogene BCL6 in diffuse large B cell lymphoma. Nature immunology 2013 Oct; 14(10).
Srinivasan SV, Dominguez-Sola D, Wang LC, Hyrien O, Gautier J. Cdc45 is a critical effector of myc-dependent DNA replication stress. Cell reports 2013 May; 3(5).
Dominguez-Sola D, Victora GD, Ying CY, Phan RT, Saito M, Nussenzweig MC, Dalla-Favera R. The proto-oncogene MYC is required for selection in the germinal center and cyclic reentry. Nature immunology 2012 Nov; 13(11).
Victora GD, Dominguez-Sola D, Holmes AB, Deroubaix S, Dalla-Favera R, Nussenzweig MC. Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas. Blood 2012 Sep; 120(11).
Dominguez-Sola D, Ying CY, Grandori C, Ruggiero L, Chen B, Li M, Galloway DA, Gu W, Gautier J, Dalla-Favera R. Non-transcriptional control of DNA replication by c-Myc. Nature 2007 Jul; 448(7152).
Dominguez-Sola D, Dalla-Favera R. Burkitt lymphoma: much more than MYC. Cancer cell 2012 Aug; 22(2).
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 Dec; 20(6).
Rossi D, Deaglio S, Dominguez-Sola D, Rasi S, Vaisitti T, Agostinelli C, Spina V, Bruscaggin A, Monti S, Cerri M, Cresta S, Fangazio M, Arcaini L, Lucioni M, Marasca R, Thieblemont C, Capello D, Facchetti F, Kwee I, Pileri SA, Foà R, Bertoni F, Dalla-Favera R, Pasqualucci L, Gaidano G. Alteration of BIRC3 and multiple other NF-κB pathway genes in splenic marginal zone lymphoma. Blood 2011 Nov; 118(18).
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 Mar; 471(7337).
Amente S, Gargano B, Varrone F, Ruggiero L, Dominguez-Sola D, Lania L, Majello B. p14ARF directly interacts with Myc through the Myc BoxII domain. Cancer biology & therapy 2006 Mar; 5(3).
Dominguez-Sola D, Dalla-Favera R. PINning down the c-Myc oncoprotein. Nature cell biology 2004 Apr; 6(4).
Tan C, Costello P, Sanghera J, Dominguez D, Baulida J, de Herreros AG, Dedhar S. Inhibition of integrin linked kinase (ILK) suppresses beta-catenin-Lef/Tcf-dependent transcription and expression of the E-cadherin repressor, snail, in APC-/- human colon carcinoma cells. Oncogene 2001 Jan; 20(1).
Barberà MJ, Puig I, Domínguez D, Julien-Grille S, Guaita-Esteruelas S, Peiró S, Baulida J, Francí C, Dedhar S, Larue L, García de Herreros A. Regulation of Snail transcription during epithelial to mesenchymal transition of tumor cells. Oncogene 2004 Sep; 23(44).
Roura S, Domínguez D. Inducible expression of p120Cas1B isoform corroborates the role for p120-catenin as a positive regulator of E-cadherin function in intestinal cancer cells. Biochemical and biophysical research communications 2004 Jul; 320(2).
Domínguez D, Montserrat-Sentís B, Virgós-Soler A, Guaita S, Grueso J, Porta M, Puig I, Baulida J, Francí C, García de Herreros A. Phosphorylation regulates the subcellular location and activity of the snail transcriptional repressor. Molecular and cellular biology 2003 Jul; 23(14).
Guaita S, Puig I, Franci C, Garrido M, Dominguez D, Batlle E, Sancho E, Dedhar S, De Herreros AG, Baulida J. Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression. The Journal of biological chemistry 2002 Oct; 277(42).
Poser I, Domínguez D, de Herreros AG, Varnai A, Buettner R, Bosserhoff AK. Loss of E-cadherin expression in melanoma cells involves up-regulation of the transcriptional repressor Snail. The Journal of biological chemistry 2001 Jul; 276(27).
Batlle E, Sancho E, Francí C, Domínguez D, Monfar M, Baulida J, García De Herreros A. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nature cell biology 2000 Feb; 2(2).
Batlle E, Verdú J, Domínguez D, del Mont Llosas M, Díaz V, Loukili N, Paciucci R, Alameda F, de Herreros AG. Protein kinase C-alpha activity inversely modulates invasion and growth of intestinal cells. The Journal of biological chemistry 1998 Jun; 273(24).
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Dr. Dominguez-Sola did not report having any of the following types of financial relationships with industry during 2014 and/or 2015: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
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