Angelina Vaseva, Ph.D.
Despite the high cure rates among children with cancer, following treatment with current multimodality therapies, survivors face profound lifelong therapy-related complications and development of second malignancies, with increasing chronic life-threatening toxicities as they age. In addition, survival rate for many high-risk pediatric cancer patients had not improved significantly over the last 30 years. Hopes for the future depend on identifying novel therapies that target specific cancer-driving cellular and molecular mechanisms, which will ensure improved survival for high-risk patients and provide better quality of life for survivors.
Components of the RAS and ERK MAPK pathways are frequently deregulated in pediatric cancers including leukemias, central nervous system tumors, and extracranial solid tumors. Our focus is to systematically define mechanisms of RAS and ERK MAPK- driven vulnerabilities in pediatric cancers and design directions for clinically relevant targeted therapeutic options. Toward these efforts we employ a wide variety of in vitro cell-based assays, unbiased genetic and pharmacologic screens as well as in vivo preclinical testing of patient-derived xenograft tumor models.
Another focus of our research is to understand how the two oncogenes RAS and MYC cooperate to promote tumor cell growth and maintenance and how we can exploit this cooperation in order to design therapeutic strategies for RAS-driven pediatric cancers. We recently demonstrated that targeting MYC degradation in RAS-driven cancers circumvents treatment adaptation. Further, we have determined that maintenance of MYC protein levels is context specific and precise evaluation in each cancer type is required. By utilizing MYC-degradation reporter we aim to identify signaling pathways and druggable targets that regulate MYC protein stability in pediatric sarcomas. Further, we will exploit our discoveries toward design of novel targeted therapeutic strategies.
- 2018 - Postdoctoral Training - University of North Carolina at Chapel Hill, North Carolina, NC, USA
- 2013 - Postdoctoral Training - Cold Spring Harbor Laboratory, Cold Spring, NY, USA
- 2012 - Ph.D. - Molecular Biology - Stony Brook University, Stony Brook, NY, USA
- 2001 - M.Sc. - Molecular Biology - Sofia University, Sofia, Bulgaria
2018 American Cancer Society postdoctoral fellowship award
2017 AACR Scholar in training award
2015 Ruth L. Kirschstein National Research Service Award (NRSA) individual postdoctoral
2014 Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training
2004 International Research Fellow Award, Dartmouth Medical School, Hanover, NH
- 5/2019 - Assistant Professor - Research - University of Texas Health Science Center at San Antonio, Greehey Children’s Cancer Research Institute, Department of Molecular Medicine, San Antonio, TX
Instruction & Training
- 01/2020 - Present, Postdoctoral fellow training, University of Texas Health Science Center at San Antonio, Greehey Children’s Cancer Research Institute
- Summer 2014, Mentoring Summer Undergraduate Research Experience (SURE) student, University of North Carolina at Chapel Hill, Chapel Hill, NC
- Spring 2014, Lecture, ‘Genetic basis of cancer’, University of North Carolina at Chapel Hill, Chapel Hill, Cell Biology Laboratory (BIO447-undergarduate)
- Spring 2008, Teaching Assistant: Biochemistry Laboratory (BIO365-undergraduate, Stony Brook University, Stony Brook, NY
- Fall 2008, Teaching Assistant: Fundamentals of Biology: Molecular and Cellular Biology (BIO202-undergarduate), Stony Brook University, Stony Brook, NY
Blake DR, Vaseva AV, Hodge RG, Kline MP, Gilbert TSK, Tyagi V, Huang D, Whiten GC, Larson JE, Wang X, Pearce KH, Herring LE, Graves LM, Frye SV, Emanuele MJ, Cox AD, Der CJ. Application of a MYC degradation screen identifies sensitivity to CDK9 inhibitors in KRAS-mutant pancreatic cancer. Sci Signal. 2019 Jul 16;12(590). PMID: 31311847
Vaseva AV, Blake DR, Gilbert TSK, Ng S, Hostetter G, Azam SH, Ozkan-Dagliyan I, Gautam P, Bryant KL, Pearce KH, Herring LE, Han H, Graves LM, Witkiewicz AK, Knudsen ES, Pecot CV, Rashid N, Houghton PJ, Wennerberg K, Cox AD, Der CJ. KRAS Suppression-Induced Degradation of MYC Is Antagonized by a MEK5-ERK5 Compensatory Mechanism. Cancer Cell. 2018 Nov 12;34(5):807-822.e7. PMID: 30423298
Waters AM, Ozkan-Dagliyan I, Vaseva AV, Fer N, Strathern LA, Hobbs GA, Tessier-Cloutier B, Gillette WK, Bagni R, Whiteley GR, Hartley JL, McCormick F, Cox AD, Houghton PJ, Huntsman DG, Philips MR, Der CJ. Evaluation of the selectivity and sensitivity of isoform- and mutation-specific RAS antibodies. Sci Signal. 2017 Sep 26;10(498). PMID: 28951536.
Klingler S, Guo B, Yao J, Yan H, Zhang L, Vaseva AV, Chen S, Canoll P, Horner JW, Wang YA, Paik JH, Ying H, Zheng H. Development of Resistance to EGFR-Targeted Therapy in Malignant Glioma Can Occur through EGFR-Dependent and -Independent Mechanisms. Cancer Res. 2015 May 15;75(10):2109-19. PMID: 25808866;
Vaseva AV, Moll UM. Identification of p53 in mitochondria. Methods Mol Biol. 2013;962:75-84. PubMed PMID: 23150438
Vaseva AV, Marchenko ND, Ji K, Tsirka SE, Holzmann S, Moll UM. p53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell. 2012 Jun 22;149(7):1536-48. PubMed PMID: 22726440. Cover Story.
Zuber J, Rappaport AR, Luo W, Wang E, Chen C, Vaseva AV, Shi J, Weissmueller S, Fellmann C, Taylor MJ, Weissenboeck M, Graeber TG, Kogan SC, Vakoc CR, Lowe SW. An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated self-renewal program as essential for leukemia maintenance. Genes Dev. 2011 Aug 1;25(15):1628-40. PMID: 21828272
Vaseva AV, Yallowitz AR, Marchenko ND, Xu S, Moll UM. Blockade of Hsp90 by 17AAG antagonizes MDMX and synergizes with Nutlin to induce p53-mediated apoptosis in solid tumors. Cell Death Dis. 2011 May 12;2:e156. PMID: 21562588.
Talos F, Abraham A, Vaseva AV, Holembowski L, Tsirka SE, Scheel A, Bode D, Dobbelstein M, Brück W, Moll UM. p73 is an essential regulator of neural stem cell maintenance in embryonal and adult CNS neurogenesis. Cell Death Differ. 2010 Dec;17(12):1816-29. PubMed PMID: 21076477
Zimmer Y, Vaseva AV, Medová M, Streit B, Blank-Liss W, Greiner RH, Schiering N, Aebersold DM. Differential inhibition sensitivities of MET mutants to the small molecule inhibitor SU11274. Cancer Lett. 2010 Mar 28;289(2):228-36. PMID: 19783361
Kimple RJ, Vaseva AV, Cox AD, Baerman KM, Calvo BF, Tepper JE, Shields JM, Sartor CI. Radiosensitization of epidermal growth factor receptor/HER2-positive pancreatic cancer is mediated by inhibition of Akt independent of ras mutational status. Clin Cancer Res. 2010 Feb 1;16(3):912-23.PMID: 20103665
Hagn F, Klein C, Demmer O, Marchenko N, Vaseva A, Moll UM, Kessler H. BclxL changes conformation upon binding to wild-type but not mutant p53 DNA binding domain. J Biol Chem. 2010 Jan 29; PMID: 19955567
Vaseva AV, Marchenko ND, Moll UM. The transcription-independent mitochondrial p53 program is a major contributor to nutlin-induced apoptosis in tumor cells. Cell Cycle. 2009 Jun 1;8(11):1711-9. PMID: 19411846
Palacios G, Crawford HC, Vaseva A, Moll UM. Mitochondrially targeted wild-type p53 induces apoptosis in a solid human tumor xenograft model. Cell Cycle. 2008 Aug 15;7(16):2584-90. doi: 10.4161/cc.7.16.6070. PMID: 18719383.
Freemantle SJ, Vaseva AV, Ewings KE, Bee T, Krizan KA, Kelley MR, Hattab EM, Memoli VA, Black CC, Spinella MJ, Dmitrovsky E. Repression of cyclin D1 as a target for germ cell tumors. Int J Oncol. 2007 Feb;30(2):333-40. PubMed PMID: 17203214
White KA, Yore MM, Warburton SL, Vaseva AV, Rieder E, Freemantle SJ, Spinella MJ. Negative feedback at the level of nuclear receptor coregulation. Self-limitation of retinoid signaling by RIP140. J Biol Chem. 2003 Nov 7;278(45):43889-92. PubMed PMID: 1450626
Vaseva AV and Yohe ME. Targeting RAS in pediatric cancer: is it becoming a reality? Curr Opin Pediatr. 2020 Feb;32(1):48-56. PMID:31815779
Vaseva AV, Moll UM. The mitochondrial p53 pathway. Biochim Biophys Acta. 2009 May;1787(5):414-20. PMID: 19007744.
Complete List of Published Work in MyBibliography: