PhD, University of Pennsylvania
At a Glance
- The focus of our group is to define which cellular and molecular niche factors regulate hematopoiesis under various insults, such as inflammation, hematopoietic malignancies, and aging.
- We use cell imaging, single-cell transcriptomics, and functional genomics to chart the molecular blueprints of the bone marrow niche and define their precise contribution to hematopoietic stress responses in mouse and man.
- Our goal is to bridge rigorous functional genomic studies of the bone marrow niche with clinical outcomes to devise rational targeted therapies for hematopoietic malignancies.
Dr. Anastasia Tikhonova completed her dissertation research in the laboratory of Dr. Alfred Singer at the National Cancer Institute, as part of the NIH-University of Pennsylvania Graduate Partnership in Immunology (2007-2011). There, she became interested in how microenvironmental factors dictate cell fate choices. Dr. Tikhonova continued her training in the laboratory of Dr. Iannis Aifantis (New York University Medical School), where she identified niche factors that govern hematopoietic stem cell differentiation and leukemia progression (2012-2019). In 2020 Dr. Tikhonova joined Princess Margaret Cancer Centre as a Scientist and is an Assistant Professor in the Dept. of Medical Biophysics at the University of Toronto.
Every functional process in our body is mediated by highly orchestrated cellular crosstalk. The bone marrow microenvironment maintains all hematopoietic cells, including stem cells (HSCs) and progenitors, though cell-cell interactions and secretion of soluble factors. The explicit goal of our research program is to delineate the mechanisms that underlie dysregulated HSC-niche crosstalk and target it to halt aberrant hematopoiesis.
In addition to hematopoietic malignancies, many other tumor types including prostate, breast and lung metastasize to and seek refuge from chemotherapy in the bone. Despite considerable advances in therapies targeting these cancers, once tumor cells have metastasized to the bone, they are generally untreatable. Our goal is to define molecular mechanisms driving bone marrow involvement in malignant processes. Understanding the cell-cell interactions that facilitate bone marrow colonization is an urgent clinical need and will allow for the targeted design of improved therapeutic strategies.
General Research Interests
- Tumor microenvironment
- Stem cell niche
- Targeted therapies for hematologic malignancies
- Guillamot M, Ouazia D, Dolgalev I, Yeung ST, Kourtis N, Dai Y, Corrigan K, Zea-Redondo L, Saraf A, Florens L, Washburn MP, Tikhonova AN, Malumbres M, Gong Y, Tsirigos A, Park C, Barbieri C, Khanna KM, Busino L, Aifantis I. The E3 ubiquitin ligase SPOP controls resolution of systemic inflammation by triggering MYD88 degradation. Nat Immunol. 2019 Sep;20(9):1196-1207.
- Tikhonova AN, Dolgalev I, Hu H, Sivaraj KK, Hoxha E, Cuesta-Domínguez Á, Pinho S, Akhmetzyanova I, Gao J, Witkowski M, Guillamot M, Gutkin MC, Zhang Y, Marier C, Diefenbach C, Kousteni S, Heguy A, Zhong H, Fooksman DR, Butler JM, Economides A, Frenette PS, Adams RH, Satija R, Tsirigos A, Aifantis I. The bone marrow microenvironment at single-cell resolution. Nature. 2019 May;569(7755):222-228.
- Saint Fleur-Lominy S, Maus M, Vaeth M, Lange I, Zee I, Suh D, Liu C, Wu X, Tikhonova A, Aifantis I, Feske S. STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic Leukemia. Cell Rep. 2018 Sep 11;24(11):3045-3060.e5.
- Pitt LA*, Tikhonova AN*, Hu H, Trimarchi T, King B, Gong Y, Sanchez-Martin M, Tsirigos A, Littman DR, Ferrando AA, Morrison SJ, Fooksman DR, Aifantis I, Schwab SR. CXCL12-Producing Vascular Endothelial Niches Control Acute T Cell Leukemia Maintenance. Cancer Cell. 2015 Jun 8;27(6):755-68.
- Van Laethem F, Tikhonova AN, Pobezinsky LA, Tai X, Kimura MY, Le Saout C, Guinter TI, Adams A, Sharrow SO, Bernhardt G, Feigenbaum L, Singer A. Lck availability during thymic selection determines the recognition specificity of the T cell repertoire. Cell. 2013 Sep 12;154(6):1326-41.
- Tikhonova AN, Van Laethem F, Hanada K, Lu J, Pobezinsky LA, Hong C, Guinter TI, Jeurling SK, Bernhardt G, Park JH, Yang JC, Sun PD, Singer A. αβ T cell receptors that do not undergo major histocompatibility complex-specific thymic selection possess antibody-like recognition specificities. Immunity. 2012 Jan 27;36(1):79-91.