Sonia Rodriguez-Rodriguez, Ph.D.
Assistant Research Professor, Department Of Stem Cell Biology And Regenerative Medicine
Research Area
Leukemia
Role Of SKP2 In Hematopoiesis And T Cell Leukemia
2005, Ph.D., Environmental Microbiology and Biotechnology, School of
Biology, University of Barcelona, Barcelona, Spain2002, M.S., Microbiology, School of Biology, University of Barcelona,
Barcelona, Spain2000, B.S., Biomedicine and Microbiology, School of Biology, University of Barcelona, Barcelona, Spain
2007-2014, Department of Pediatrics, Wells Center and Indiana
University School of Medicine, Indianapolis, IN
2016-present, Assistant Research Professor, City of Hope, Duarte, CA
2014-2016, Assistant Research Professor, Indiana University School of Medicine, Indianapolis, IN
The long-term goal of my research is to better understand the mechanisms involved in the regulation of normal and malignant hematopoietic stem cells that would lead to the identification of novel approaches for treating bone marrow failures and leukemias. Dr. Carlesso’s laboratory has been focused for several years on understanding how the Notch signaling pathway senses the microenvironment and contributes to hematopoietic stem cell regulation. Specifically, my research activity in the past few years has being focused on understanding the mechanisms that control cell fate decisions, self-renewal and differentiation of hematopoietic stem cells, especially in response to stress. More in particular, I have being studying the role of SKP2 in hematopoiesis.
SKP2 is an important regulator of the cell cycle and has being studied in depth in several cellular systems. SKP2 transcription is regulated by the Notch family of protein receptors, and our recent studies show that SKP2 deficiency enhances HSC quiescence. As little is known about the role of SKP2 in leukemia, I recently started to explore the role of SKP2 in T cell leukemia. The majority of T cell leukemia is characterized by the constitutive activation of the Notch signaling pathway. However, little is known about the downstream mediators involved in the disease progression and relapse. Our laboratory has a wide experience with “in vivo” Notch-induced mouse and xenograft models. My previous results with those models show that the increase in Notch signaling correlates with an overexpression of SKP2, and an increase cell cycle. On the other hand, genetic ablation of SKP2 increases survival and delays disease progression, revealing for the first time the important role of SKP2 in leukemias, and making SKP2 a suitable target for new drug therapies. Our findings on SKP2 and leukemia, together with the discovery of new small compounds inhibiting SKP2 function, lead to the possibility of a new potential use of SKP2 inhibitors in the treatment of T-ALL.
2009, American Society of Hematology Travel Award (now Abstract Achievement)
2011, American Society of Hematology Abstract Achievement Award
2013 American Society of Hematology Abstract Achievement Award
2002-2005, Member, Spanish Association of Microbiology, Spain
2009-2011, Member, International Society of Stem Cell Research
2012-2014, Member, American Society of Hematology
2009-Present, Member, F1000 Faculty Prime
2018-Present, Member, International Society for Experimental Hematology
- Nieto JM, Madrid C, Miquelay E, Parra JL, Rodriguez S, Juarez A. Evidence for Direct Protein-Protein Interaction between Members of the Enterobacterial Hha/YmoA and H-NS Families of Proteins. Journal of Bacteriology 184: 629-635. (2002).
- Pons JI, Rodriguez S, Madrid C, Juarez A, Nieto JM. In vivo increase of solubility of overexpressed Hha protein by tandem expression with interacting protein H-NS. Protein expression & purification 35: 293-297. (2004).
- Rodriguez S, Nieto JM, Madrid C, Juarez A. Functional replacement of the oligomerization domain of H-NS by the Hha protein of Escherichia coli. Journal of Bacteriology 187: 5452-5459. (2005).
- Abella M, Rodriguez S, Paytubi S, Campoy S, White MF, Barbé J. The Sulfolobus solfataricus radA paralogue sso0777 is DNA damage inducible and positively regulated by the Sta1 protein. Nucleic acid research 35: 6788-6797. (2007).
- Fernandez L, Rodriguez S, Huang H, Chora A, Mumaw C, Cruz E, Pollok K, Cristina F, Krause DS, Price JE, Ferkowicz MJ, Scadden DT, Clauss M, Cardoso AA, Carlesso N. TNF and endothelial cells modulate Notch signaling in the bone marrow microenvironment during inflammation. Experimental hematology 36(5):545-558. (2008).
- Rodriguez S, Chora A, Goumnerov B, Mumaw C, Goebel S, Fernandez L, Baydoun H, HogenEsch H, Dombkowski DM, Karlewicz CA, Rice S, Rahme LG, Carlesso N. Dysfunctional expansion of hematopoietic stem cells and block of myeloid differentiation in lethal sepsis. Blood. 114(19):4064-4076. (2009).
- Chitteti BR, Cheng YH, Poteat B, Rodriguez-Rodriguez S, Goebel WS, Carlesso N, Kacena MA, Srour EF. Impact of interactions of cellular components of the bone marrow microenviroment on hematopoiesic stem and progenitor cell function. Blood. 115(16):3239-48. (2010).
- Chitteti BR, Cheng YH, Streicher DA, Rodriguez-Rodriguez S, Carlesso N, Srour EF, Kacena MA. Osteoblast lineage cells expressing high levels of Runx2 enhance hematopoetic progenitor cell proliferation and function. Journal of Cellular Biochemistry. 111(2):284-94. (2010).
- Cheng YH,* Chitteti BR,* Streicher DA, Morgan JA, Rodriguez-Rodriguez S, Carlesso N, Srour EF, Kacena MA. Impact of osteoblast maturational status on their ability to enhance the hematopoietic function of stem and progenitor cells. Journal of Bone Mineral Research. 26(5):111-1121. (2011).
- Rodriguez S, Wang L, Mumaw C, Srour EF, Lo Celso C, Nakayama K, Carlesso N. The SKP2 E3 Ligase regulates basal homeostasis and stress induced regeneration of hematopoietic stem cells. Blood. 117(24):6505-6519. (2011).
- Wang L, Zhang H, Rodriguez S, Cao L, Parish J, Mumaw C, Zollman A, Kamoka MM, Mu J, Chen DZ, Srour EF, Chitteti BR, Hoegenesh H, Tu X, Bellido TM, Boswell HS, Manshouri T, Verstovsek S, Yoder MC, Kapur R, Cardoso AA, Carlesso N. Notch-dependent repression of miR-155 in the bone marrow niche regulates hematopoiesis in an NF-kB-dependent manner. Cell Stem Cell. 15(1):51-65. (2014).
- Zhang H, Rodriguez S, Wang L, Wang S, Serezani H, Kapur R, A Cardoso AA, Carlesso N. Activation of TRIF-dependent signaling causes hematopoietic stem cell exhaustion during sepsis. Stem Cell Reports. 6(6):940-956. (2016).
- Kobayashi M, Nabinger SC, Bai Y, Yoshimoto M, Gao R, Chen S, Yao C, Dong Y, Zhang L, Rodriguez S, Yashiro-Ohtani Y, Pear WS, Carlesso N, Yoder MC, Kapur R, Kaplan MH, Lacorazza H, Zhang ZY, Liu Y. Protein Tyrosine Phosphatase PRL2 mediates Notch and Kit signals in early T-cell progenitors. Stem Cells. 35(4):1053-1064. (2017).
- Batista A*, Rodriguez S*, Ding J, Shou W, Carlesso N, Cardoso A. Notch signaling is sustained by leukemia microenvironment and modulates IL-7 signals in T-ALL. * Equal contribution. Submitted
- Rodriguez S, Wang L, Zhang H, Mehrota P, Zollman A, Kaplan MH, Sandusky G, Chiang GM, Mulloy JC, Wunderlich M, Palmer J, Yui MA, Cardoso AA, Carlesso N. Loss of the E3 ubiquitin ligase SKP2 limits the oncogenic potential of Notch in T-ALL. Submitted.