Programs
Departments & Divisions
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Research
Yuzuru Shiio, M.D., Ph.D.
Associate Professor
Biochemistry & Structural Biology
Greehey Children's Cancer Research Institute
Currently seeking Ph.D. students
I was initially trained as a physician and have broad knowledge of clinical medicine. As a PhD student, I received extensive training in molecular cell biological study of p53, Rb, and NF-κB. As a postdoctoral fellow with Dr. Robert Eisenman at Fred Hutchinson Cancer Research Center, I carried out cancer biology research focusing on the Myc network of transcription factors. During this time, I developed my interest in proteomics and initiated collaboration with Dr. Ruedi Aebersold at the Institute for Systems Biology. Later as a Senior Scientist in his lab, I continued proteomics research on Myc and related proteins.
As an independent investigator, I developed my research program on the proteomic and functional characterization of the VHL-HIF pathway (R01CA125020), identification of secreted biomarkers for VHL-mutated tumors (R21CA137568), and dissection of protein secretion from senescent cells, which led to the identification of IGFBP3 and SFRP1 cytokines as secreted mediators of senescence (R21AG029587, published in PNAS and MCB). Because IGFBP3 is an important transcriptional repression target of EWS-FLI1 in Ewing sarcoma, we initiated a research project to exploit the senescence-inducing activity of IGFBP3 for therapy of Ewing sarcoma. We reported that FLI1-EWS, a fusion protein reciprocal to EWS-FLI1, plays an important role in Ewing sarcoma (G&C, 2015), which led to a new R21 grant (R21CA202485). Using interactome proteomics, we discovered that EWS-FLI1 is degraded by the lysosome in Ewing sarcoma (JPR, 2014), which resulted in a CPRIT HIHR award. Using secretome proteomics, we discovered that Ewing sarcoma depends on two novel cytokine signaling pathways, which resulted in two CPRIT IIRACCA awards ($300k direct cost/year x 4 years each).
Our laboratory uncovered three novel cytokine signaling pathways important in children's cancers and continues to dissect the signaling mechanisms and explore the approaches to target these pathways. 1) GDF6-CD99-CSK-Src signaling in Ewing sarcoma and Klippel-Feil syndrome (Cell Reports 33(5): 108332, 2020; CPRIT IIRACCA award $300k direct cost/year, 2016 - 2021). 2) NELL2-Robo3-cdc42-BAF complex signaling in Ewing sarcoma and other pediatric cancers (Cell Reports 36(1): 109254, 2021; CPRIT IIRACCA award $300k direct cost/year, 2019 - 2023), and 3) SFRP2-CXADR-nitric oxide signaling in retinoblastoma (Cell Reports 42(2):112103, 2023).
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Professional Background
Education
- MD - Medicine - University of Tokyo
- Ph.D. - Molecular Biology - University of Tokyo
- Postdoctoral Fellowship - Cancer Biology - Fred Hucthinson Cancer Research Center
- Senior Scientist - Proteomics - Institute for Systems Biology
Highlights
I am interested in applying proteomics and molecular biology to discover novel cytokine – receptor signaling pathways important in human health and diseases. I believe that there remain a number of undiscovered cytokine signaling pathways that can be discovered by secretome and cell surface proteomics. This hypothesis is supported by our discoveries of novel cytokine pathways important in pediatric cancers. These cytokine pathways provide excellent opportunities for therapeutic targeting.
Appointments
- 9/2013 - Associate Professor - UTHSCSA, Biochemistry, San Antonio
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Instruction & Training
- 4/2008 - Present, Post-Doctoral Student Supervision, UTHSCSA
- 9/2014 - Present, Fundamentals of Biomedical Sciences, The University of Texas Health Science Center
- 3/2012 - Present, BIOC6037 Integration of Metabolic Pathways, UTHSCSA
- 8/2011 - Present, Membership on Supervising Committee, UTHSCSA
- 3/2008 - Present, BIOC6010 Gene Expression, UTHSCSA
- 4/2017 - Present, INTD6033 Cell Signaling, UTHSCSA
- 10/2016 - Present, MINE6004 Biology for Bioengineers, UTHSCSA
- 9/2014 - Present, Dental Biochemistry (BIOC5013, DHHD5001), UTHSCSA
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Research & Grants
Our laboratory uncovered three novel cytokine signaling pathways important in children's cancers, and continues to dissect the signaling mechanisms and explore the approaches to target these pathways. 1) GDF6-CD99-CSK-Src signaling in Ewing sarcoma and Klippel-Feil syndrome (Cell Reports 33(5): 108332, 2020; CPRIT IIRACCA award $300k direct cost/year, 2016 - 2021). 2) NELL2-Robo3-cdc42-BAF complex signaling in Ewing sarcoma and other pediatric cancers (Cell Reports 36(1): 109254, 2021; CPRIT IIRACCA award $300k direct cost/year, 2019 - 2023), and 3) SFRP2-CXADR-nitric oxide signaling in retinoblastoma (Cell Reports 42(2):112103, 2023).
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Service
Department
Grant Review Committee (2013 - Present)
GCCRI Seminar Series Committee (2019 - Present)
School
IBMS Admission Committee (2015 - 2017)
IBMS Curriculum Committee (2019 - Present)
Institutional
UTHSCSA Institutional Biosafety Committee (2006 - Present)
UT System Biosafety Committee (2006 - 2014)
UTHSCSA Institutional Review Entity (2017 - Present)
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Publications
- Nitric oxide suppression by secreted frizzled-related protein 2 drives retinoblastoma
- Slit2 signaling stimulates Ewing sarcoma growth
- EZH2 suppresses endogenous retroviruses and an interferon response in cancers
- Loss of MGA repression mediated by an atypical polycomb complex promotes tumor progression and invasiveness
- NELL2-cdc42 signaling regulates BAF complexes and Ewing sarcoma cell growth.
- GDF6-CD99 Signaling Regulates Src and Ewing Sarcoma Growth
- MYC Regulation of D2HGDH and L2HGDH Influences the Epigenome and Epitranscriptome
- EWS-FLI-1 creates a cell surface microenvironment conducive to IGF signaling by inducing pappalysin-1
- FGF19 functions as autocrine growth factor for hepatoblastoma
- Role of galactose in cellular senescence
- The role of FLI-1-EWS, a fusion gene reciprocal to EWS-FLI-1, in Ewing sarcoma
- Proteomic Analysis of the EWS-Fli-1 Interactome Reveals the Role of the Lysosome in EWS-Fli-1 Turnover
- Wnt antagonist SFRP1 functions as a secreted mediator of senescence
- Plasminogen activator inhibitor 1--insulin-like growth factor binding protein 3 cascade regulates stress-induced senescence
- The interaction of the von Hippel-Lindau tumor suppressor and heterochromatin protein 1
- Quantitative proteomic identification of the BRCA1 ubiquitination substrates
- Proteomic dissection of the von Hippel-Lindau (VHL) interactome
- Quantitative proteomics identifies the Myb-binding protein p160 as a novel target of the von Hippel-Lindau tumor suppressor
- Identification and characterization of SAP25, a novel component of the mSin3 corepressor complex
- Quantitative proteome analysis using isotope-coded affinity tags and mass spectrometry
- Quantitative proteomic analysis of myc-induced apoptosis: a direct role for Myc induction of the mitochondrial chloride ion chan
- Histone sumoylation is associated with transcriptional repression
- Quantitative proteomic analysis of chromatin-associated factors
- Quantitative proteomic analysis of Myc oncoprotein function