My laboratory has a long-standing interest in pathobiology of solid and hematopoietic malignancies, in particular lymphomas and leukemias and other cancers driven by MYC overexpression. I trained in the MYC field in the early ‘90s as post-doctoral Research Associate and then Leukemia Society Special Fellow at the renowned Fred Hutchinson Cancer Research Center in Seattle. In 1997, I was recruited to the University of Pennsylvania, where I rose through the ranks to become tenured Professor of Pathology & Laboratory Medicine. For over 18 years, I have been continuously funded by NCI, beginning with the NIH FIRST Award (R29) and ending with 1 R01 and 2 R21s that are currently active. In addition, I have received grants from numerous private foundations including American Cancer Society, Swiss Cancer League, Leukemia & Lymphoma Society, Alex's Lemonade Stand Foundation, WW Smith Charitable Trust, The V Foundation, and William Lawrence and Blanche Hughes Foundation. This robust extramural support allowed me to maintain an active lab, currently composed of one Scientist, four postdoctoral fellows, three graduate students, one undergraduate student, and one technician. We publish our work in top-notch journals, including Nature Genetics, Nature Immunology, Journal of Clinical Investigation, Journal of the National Cancer Institute, Blood, Cancer Research, etc. Of the Top 10 most frequently cited 2005-2014 MYC papers , my laboratory co-authored 3, which were cited >1,700 times.
Several years ago, I moved my lab across campus to The Children's Hospital of Philadelphia, where it became an integral part of the Center for Childhood Cancer Research. This integration allowed me to foster new collaborations with key physician-scientists and pursue several translational projects. Because of my prior contributions to the field of immunobiology, in 2013 I became Investigator of the multi-institutional Stand Up to Cancer-St. Baldrick's Pediatric Cancer Dream Team. In 2015, I was invited to represent the entire SU2C group at the Annual AACR meeting and gave a plenary talk on the role of alternative splicing of CD19 in resistance to CART-19 immunotherapy (subsequently published in Cancer Discov). This and other partnerships solidified my commitment to team science, of which the current application is but the most recent example.
Sotillo E, Barrett DM, Black KL, Bagashev A, Oldridge D, Wu G, Sussman R, Lanauze C, Ruella M, Gazzara MR, Martinez NM, Harrington CT, Chung EY, Perazzelli J, Hofmann TJ, Maude ML, Raman P, Barrera A, Gill S, Lacey LF, Melenhorst JJ, Allman D, Jacoby E, Fry T, Mackall C, Barash Y, Lynch KW, Maris JM, Grupp SA, Thomas-Tikhonenko A. Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov. 2015 December; 5:12. [EDITORS' CHOICE: S. Behjati "Hiding from the enemy", Science Translational Medicine, 7 (313), 313ec193 (2015) | RESEARCH HIGHLIGHT: G.K.Alderton "Skipping out epitopes", Nature Reviews Cancer, 15, 699 (2015) | IN THE SPOTLIGHT: H.J. Jackson & R.J.Brentjens "Overcoming Antigen Escape with CAR T-cell Therapy", Cancer Discov, 5:1238 (2015)]
Education and Training
Retrovirology - Fred Hutchinson Cancer Research Center, Seattle, WA
PhD in Oncology/Virology - Russian Academy of Medical Sciences, Moscow, Russia
Titles and Academic Titles
Chief, Division of Cancer Pathobiology
Professor of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania
Areas of Focus
- Aberrant Splicing in Lymphoid Malignancies and its Implications for Immunotherapy
- Harnessing the Pro-apoptotic Activity of Myc for Therapeutic Purposes
- The Key Role of the B-cell Receptor (BCR) Pathway in Lymphoid Malignancies
Laboratories & Research Programs
E. Sotillo, D.M. Barrett, K.L. Black, A. Bagashev, D. Oldridge, G. Wu, R. Sussman, C. Lanauze, M. Ruella, M.R. Gazzara, N.M. Martinez, C.T. Harrington, E.Y. Chung, J. Perazzelli, T.J. Hofmann, S.L. Maude, P. Raman, A. Barrera, S. Gill, S.F. Lacey, J.J. Melenhorst, D. Allman, E. Jacoby, T. Fry, C. Mackall, Y. Barash, K.W. Lynch, J.M. Maris, S.A. Grupp, and Andrei Thomas-Tikhonenko: Convergence of acquired mutations and alternative splicing of CD19 confers resistance to CART-19 immunotherapy. under re-review 2015.
M.Dews, G.S. Tan, S. Hultine, P. Raman, J. Choi, E.K. Duperret, J. Lawler, A. Bass, and A. Thomas-Tikhonenko: Masking epistasis between MYC and TGFβ pathways in anti-angiogenesis mediated colon cancer suppression. J Natl Cancer Inst 106(4): dju043, April 2014.
Psathas JN, Doonan PJ, Raman P, Freedman BD, Minn AJ, Thomas-Tikhonenko A. The Myc-miR-17-92 axis amplifies B-cell receptor signaling via inhibition of ITIM proteins: a novel lymphomagenic feed-forward loop. Blood 122(26): 4220-4229, Dec 2013.
Fox JL, Dews M, Minn AJ, Thomas-Tikhonenko A. Targeting of TGFβ signature and its essential component CTGF by miR-18 correlates with improved survival in glioblastoma. RNA 19(2): 177-190, Feb 2013. Read the abstract
V.Pillai, E.Sotillo, C.Harrington, G.Wertheim, S.L.Maude, S.R.Rheingold, M.Paessler, A.Thomas-Tikhonenko, and S.A. Grupp: Changes in CD19 localization after CD19-directed chimeric antigen receptor T cell therapy for primary mediastinal large B cell lymphoma. Br J Haematol 171(S1): 85, 2015 Notes: Proceedings of Fifth International Symposium on Childhood, Adolescent and Young Adult Non-Hodgkin Lymphoma, Varese, IT.
Sotillo E, Barrett DM, Black KL, Bagashev A, Oldridge D, Wu G, Sussman R,Lanauze C, Ruella M, Gazzara MR, Martinez NM, Harrington CT, Chung EY, Perazzelli J, Hofmann TJ, Maude SL, Raman P, Barrera A, Gill S, Lacey SF, Melenhorst JJ, Allman D, Jacoby E, Fry T, Mackall C, Barash Y, Lynch KW, Maris JM, Grupp SA,Thomas-Tikhonenko A.: Alternative splicing of CD19 mRNA in leukemias escaping CART-19 immunotherapy eliminates the cognate epitope and contributes to treatment failure. AACR Annual Meeting 2015.
Danika M. Johnston*, Elena Sotillo-Piñeiro*, Linh Le, Lee D. McDaniel, Pichai Raman, Ariella Sasson, Liu Xu, Travis Laver, Edward Attiyeh, Kristina Cole, John M. Maris, Sharon Diskin & Andrei Thomas-Tikhonenko: 3'UTR SNPs that are targets for A-I RNA editing control IGF1R mRNA expression levels in high-risk neuroblastoma. International Conference on the Long and the Short of Non-Coding RNAs 2015.
Cancer genome and tumor microenvironment. A. Thomas-Tikhonenko (eds.). Springer, 2009.
P. Sundaram, C.V. Dang, and A. Thomas-Tikhonenko: Myc and control of tumor neovascularization Cancer Genome and Tumor Microenvironment. A. Thomas-Tikhonenko (eds.). Springer New York, 2009.
A. Thomas-Tikhonenko: Hardwiring tumor progression Cancer Genome and Tumor Microenvironment. A. Thomas-Tikhonenko (eds.). Springer New York, 2009.
Posters and Presentations
Thomas-Tikhonenko A. 4th International Aegean Conference on Tumor Microenvironment and Cellular Stress; 2016 Jun; Rhodes, Greece.
Thomas-Tikhonenko A. Post-transcriptional regulation of the BCR pathway in neoplastic B-cells [presentation]. 2nd American Society of Hematology (ASH) Meeting on Lymphoma Biology; 2016 Jun; Colorado Springs, CO.
Thomas-Tikhonenko A. Imprecise transcription of cancer genome: from alternative splicing to selective editing [presentation]. Wake Forest Comprehensive Cancer Center Seminar Series; 2015 Sep; Winston-Salem, NC.
Thomas-Tikhonenko A. The role of alternative splicing in leukemia immunoediting [presentation]. 1st International Aegean Conference "The long and the short of non-coding RNAs; 2015 Jun; Chania, Crete, Greece.
Thomas-Tikhonenko A. Pediatric Cancer Dream [presentation]. Team SU2C Scientific Session: Translating advances in immunotherapy to patient benefit. 2015 AACR Annual Meeting; 2015 Apr; Philadelphia, PA.
Thomas-Tikhonenko A. MicroRNAs that control the PI3K survival pathway [presentation]. microRNA as Biomarkers & Diagnostics 2015 Cambridge Healthtech Institute Conference; 2015 Mar; Cambridge, MA.
Thomas-Tikhonenko A. CD19: Marker or maker of B-lymphoid malignancies? [presentation]. City of Hope Cancer Center Seminar Series; 2015 Feb; Duarte, CA.
Thomas-Tikhonenko A. The MYC-microRNA pathway in B-cell neoplasms [presentation]. AACR Special Conference on MYC: From Biology to Therapy; 2015 Jan; La Jolla, CA.
Thomas-Tikhonenko A. Regulation of IGF1R Expression and Signaling by Polymorphisms in 3'UTR in Neuroblastoma: Implications for Therapy [presentation]. microRNA World 2014, Hanson Wade Conference; 2014 Oct; Boston, MA.
Thomas-Tikhonenko A. The role of TGFbeta in colon cancer progression [presentation]. Fusion Conference on Biology and Treatment of Metastatic Cancers; 2014 Sep; El Jadida, Morocco.
Thomas-Tikhonenko A. Pro-Angiogenic MicroRNAs in Colorectal Cancer: Lessons from Mouse Models and Cancer Genomics [presentation]. 4th International Conference on Tumor Progression and Therapeutic Resistance; 2014 Mar; Boston, MA.
Awards and Honors
2013-2017, Immunogenomics Pediatric Dream Team Investigator, Stand Up To Cancer - St. Baldrick's Foundation
2013, Ethel Brown Foerderer Fund for Excellence Award
2012, Department of Cancer Biology 4th Annual Award for Excellence in Teaching, Perelman School of Medicine at the University of Pennsylvania
2011-present, Mildred L. Roeckle Endowed Chair in Pathology at The Children's Hospital of Philadelphia
2010-2013, Innovation Award, Alex's Lemonade Stand Foundation
2005, Pfizer Award for Research Excellence, Pfizer Animal Health
2000-present, Honorary Member of the Phi Zeta Honor Society of Veterinary Medicine (Beta Chapter)
1999-2005, Elizabeth & William Whitney Clark Developmental Chair in Oncology, University of Pennsylvania
1997-2002, NIH FIRST Award
1996, Travel Award, American Society for Microbiology
1995, Travel Award, Fundación Juan March
1994-1997, Special Fellow, Leukemia Society of America
1990, ICRETT Award (short-term exchange), International Union Against Cancer
Editorial and Academic Positions
2014-present, Oncoscience (Impact Journals), Editorial Board Member
2013-present, BMC Biology Direct, Editorial Board Member
2012-present, American Journal of Cancer Research, Senior Editorial Board Member
2011-present, Frontiers in Non-Coding RNA, Editorial Board Member
2010-present, Journal of Clinical Investigation, Associate Editor
2009-2012, Hem-Onc, Editorial Board Member
2007-present, Cancer Microenvironment, Editorial Board Member
2001-present, Cancer Biology & Therapy, Editorial Board Member / Receiving Editor
Academic and institutional committees
2015, Steering Committee, Center for Childhood Cancer Research
2015-present, Faculty Advisory Committee on Compliance
2015-present, Faculty Mentoring Committee for Dr. Vinodh Pillai
2015-present, Strategic Planning Executive Committee, Center for Childhood Cancer Research
2015-present, Laboratory/Translational Researchers Search Committee, Center for Childhood Cancer Research
2014-present, Internal Advisory Board, T32 CA009140 "Immunobiology of normal and neoplastic lymphocytes"
2014-present, K99/R00 Mentoring Committee for Dr. Michael Russell
2014-present, K08 Advisory Committee for Dr. Robert Schnepp
2013-present, Member, Department of Pathology & Laboratory Medicine Academic Appointments and Promotions Committee (AAPC)
2013-present, Faculty Mentoring Committee for Dr. Marc Vermulst, chair
2012-present, Swiss National Science Foundation, Grant Reviewer
2012-present, Member, Sarcoma Researcher Search Committee, Abramson Family Cancer Research Institute - Center for Childhood Cancer Research
2012-2013, NCI Special Emphasis Panels: Omnibus R03/R21, Grant Reviewer
2012, NCI Special Emphasis Panel: Collaborative Research in Integrative Cancer Biology and the Tumor Microenvironment (U01), Grant Reviewer
2010-present, Department of Pathology, Children's Hospital of Philadelphia, executive committee
Leadership and Memberships
Memberships in Professional Organizations
2014, Qatar National Research Fund (QNRF), grant reviewer
2014, Austrian Science Fund (FWF), grant reviewer
2013-2014, Regulatory Genomics Special Interest Group (RegGenSIG) Advisory Committee
2012-2014, Swiss National Science Foundation, grant reviewer
2007-present, International Cancer Microenvironment Society
2007-2015, Cancer Research UK, grant reviewer
2005-2014, Italian Association for Cancer Research, grant reviewer
2015, NCI Outstanding Investigator Award (R35) Special Emphasis Panel, grant reviewer
2014-2015, St. Baldrick's Foundation, grant reviewer
2014, NCI Subcommittee I - Transition to Independence, grant reviewer
2012-2015, NCI Special Emphasis Panels: Omnibus R03/R21, grant reviewer
- 2015, co-chair
2010-2014, NCI Special Emphasis Panels: Program Project Grants (P01), grant reviewer
2009-present, Alex's Lemonade Stand Foundation
- Scientific Review Board
2008-present, American Society of Hematology
1999-present, American Association for Cancer Research
- 2013-2015, Member of the AACR Basic Cancer Research Fellowships Scientific Review