Dr. Ana Banito
Group leader "Soft-tissue sarcoma"
German Cancer Research Center
Div. Pediatric Neurooncology / G706
Im Neuenheimer Feld 280
Sarcomas are an extremely heterogeneous group of mesenchymal tumors that arise in a multitude of tissues from many different cell types. Several genetic events have been identified in different sarcoma sub-types, but very few models were developed to study their role in tumorigenesis aiming at exploiting them as therapeutic vulnerabilities. As a result, the treatment of sarcoma has had extremely limited advancement in treatment options compared to other cancers. Thus, the generation of in vitro and in vivo models for sarcoma research is urgently needed, to provide insights into the pathobiology of these tumors and discover novel vulnerabilities in these often lethal but yet understudied diseases.
A common molecular mechanism
Many types of soft tissue sarcomas arising in children and young adults have a unifying underlying genetic mechanism, where chromosomal translocations generate fusion oncoproteins that serve as drivers of the disease. This genetic simplicity provides an exceptional opportunity to develop effective and specific therapies. My past research has applied cutting edge technology to define epigenetic vulnerabilities associated with the SS18-SSX gene fusion, the defining event in synovial sarcoma, and to study its chromatin occupancy genome-wide. Our current goal is to combine a toolbox consisting of CRISPR/Cas9, RNAi technology and mouse modeling tools to systematically address key genetic and epigenetic mechanisms in the pathobiology of pediatric sarcomas. Our goal is to comprehensively study the impact of gene fusions and other genetic drivers in sarcomagenesis, uncover specific vulnerabilities they create, ultimately aiming at maximizing the potential for rapid clinical translation.
1. Banito A, Li X, Laporte A, Roe JS, Sanchez-Vega F, Huang CH, Dancsok A, Hatzi K, Chen CC, Tschaharganeh DF, Chandwani R, Tasdemir N, Ladanyi M, Jones KB, Capecchi MR, Vakoc CR, Torsten N, Lowe SW. The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma. Cancer Cell. 2018 Mar 12;33(3):527-541.
2. Tasdemir N*, Banito A*, Roe JS*, Alonso-Curbelo D*, Camiolo M, Tschaharganeh DF, Huang CH, Aksoy O, Bolden JE, Chen C, Fennell M, Chicas A, Vakoc C, Lowe SW. Brd4 connects enhancer remodeling to senescence immune surveillance. Cancer Discov. (2016) June; 6(6): 612-29.
3. Acosta JC*, Banito A*, Wuestefeld T, Georgilis A, Janich P, Morton JP, Athineos D, Kang TW, Lasitschka F, Andrulis M, Pascual G, Morris KJ, Khan S, Jin H, Dharmalingam G, Snijders AP, Carroll T, Capper D, Pritchard C, Inman GJ, Longerich T, Sansom OJ, Benitah SA, Zender L, Gil J. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol. (2013) Aug;15(8):978-90.
4. Banito A, Rashid ST, Acosta JC, Li S, Pereira CF, Geti I, Pinho S, Silva JC, Azuara V, Walsh M, Vallier L, Gil J. Senescence impairs successful reprogramming to pluripotent stem cells. Genes Dev (2009) 23, 2134-2139.
5. Acosta JC, O’Loghlen A, Banito A, Guijarro MV, Augert A, Raguz S, Fumagalli M, Da Costa M, Brown C, Popov N, Takatsu Y, Melamed J, d'Adda di Fagagna F, Bernard D, Hernando E, Gil J. (2008). Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell. (2008) 133, 1006-1018.