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John M. Perry, PhD

TitleResearch Faculty PhD
InstitutionChildren's Mercy Kansas City
DepartmentPediatrics
Address2401 Gillham Rd
Kansas City MO 64108
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    Other Positions
    TitleAssistant Professor of Pediatrics
    InstitutionUniversity of Missouri-Kansas City
    DepartmentPediatrics

    TitleResearch Assistant Professor of Pediatrics
    InstitutionUniversity of Kansas Medical Center
    DepartmentPediatrics


    Collapse Biography 
    Collapse education and training
    Wright State University, Dayton, OH USABS2000Biology and Chemistry
    Penn State University, University Park, PA USAPhD2006Cell and Developmental Biology

    Collapse Overview 

    Collapse Research 
    Collapse research overview
    Dr. Perry's studies stem cells, cancer, immunology, and experimental therapeutics. While these seem like disparate fields, the lab has found surprising connections between them.

    Regarding stem cells, they study how normal blood-forming (hematopoietic) stem cells expand by making more of themselves, a process called self-renewal. They found that self-renewal was guided by the simultaneous activation of two genetic signaling pathways, Wnt/beta-catenin and PI3K/Akt. Pharmacological activation of these pathways drives the expansion of HSCs in culture, which are expected to be useful for therapy.

    In studying self-renewal, they made a mouse model that permanently activated the genetic pathways mentioned above by mutation. This resulted in the development of leukemia stem cells (LSCs), which are resistant to therapy and cause relapse. Since LSCs are particularly reliant on the interaction between Akt and beta-catenin, they did a high-throughput drug screen to discover inhibitors of this interaction. Surprisingly, a long-used chemotherapy drug, doxorubicin, would inhibit this interaction at very low doses. So, they repurposed doxorubicin as a targeted therapy against LSCs rather than a broadly toxic drug.

    By investigating the mechanism underlying doxorubicin's ability to target LSCs, they found that low-dose but not high-dose doxorubicin activated anti-cancer immunity. They are currently studying the details of this process and how they might 'immunize' pediatric patients against cancer relapse.
    Collapse research activities and funding
         (John M. Perry)Nov 1, 2018 - Oct 31, 2021
    Braden's Hope
    Overcoming therapeutic resistance by repurposing a classic chemotherapeutic drug as a targeted therapy to reactivate anti-cancer immunity
    Role Description: The idea behind this study is that the cells responsible for relapse in pediatric patients can be eliminated by repurposing a chemotherapy drug, doxorubicin (DXR), as a targeted therapy to restore anti-cancer immunity against minimal residual disease (MRD) and therapy-resistant LSCs while avoiding broad toxicity and the evolution of resistance. Completion of this project is expected to provide durable cures for pediatric patients at risk for relapse and to do so in a manner that does not result in early death related to the therapy itself.
    Role: Principle Investigator

         (John M. Perry)Nov 1, 2019 - Oct 31, 2022
    Noah's Bandage Project
    Harnessing the Immune System to Fight Pediatric Cancer: Discovering Novel Inducers of Immunogenic Cell Death
    Role Description: Treatment of pediatric cancercurrently involvesthe use of high doses of toxic drugs, which result in severe side-effects. These side-effects result in 80% of long-term pediatric cancer survivors having one or more disabling or life-threatening health conditions by age 45. Secondary cancersunrelated to the originalmalignancycan also occur, and 20% of pediatric cancer patientsdo not survive long-term.Immunotherapy usingimmune checkpoint(IC)inhibitorshas shown great promise recently for certain adult cancers; however, these advances havelargely notbeen applicable to pediatric cancers. Our preliminary studies reveal a path toward changing this. Specifically, we and others have found that the Wnt/ß-catenin and PI3K/Akt pathways cooperatively promote tumorigenesis, stem cell proliferation, and resistance to anti-cancer therapies, including immunotherapy. Doxorubicin (DXR), a long-used chemotherapy drug was unexpectedlyfound to be a specificinhibitor of Akt:ß-catenin interaction at very low doses. We found that Akt-activated ß-catenin binds promoters of multiple IC genes, which are expressed specifically in therapy-resistant leukemia stem cells (LSCs). Thus, we repurposed DXR as a targeted inhibitor rather than a broadly cytotoxic chemotherapy. In contrast tothe typical clinical usage, low-dose DXR treatment inhibitsexpression of multiple ICs and stimulates immunogenic cell death (ICD)in otherwise therapy-resistant LSCs. Unlike other forms of cellular death, ICDcan induceananti-cancer immune response, effectively immunizing against cancer recurrence. Unfortunately, this effect is limited and typically not curative without additionof highly cytotoxic therapy. Here, we will test the hypothesis, supported by preliminary data,that low-dose DXRinitiatesan ICDprogram, the mechanism of whichcan be discovered using cutting-edge whole genomeCRISPR/Cas9-based chemical/genetic screens. This project will construct and validate such a screen to discover antagonists and synergists of ICD vs. therapy resistance. Ultimately, this project willreveal novel therapeutic strategies for harnessing the immune systemto enhance and potentiate the ICD response of low-dose DXR treatment, thus providingdurable, less toxic cures for pediatric cancer.
    Role: Principle Investigator

    Collapse Bibliography 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Perry JM, Tao F, Roy A, Lin T, He XC, Chen S, Lu X, Nemechek J, Ruan L, Yu X, Dukes D, Moran A, Pace J, Schroeder K, Zhao M, Venkatraman A, Qian P, Li Z, Hembree M, Paulson A, He Z, Xu D, Tran TH, Deshmukh P, Nguyen CT, Kasi RM, Ryan R, Broward M, Ding S, Guest E, August K, Gamis AS, Godwin A, Sittampalam GS, Weir SJ, Li L. Overcoming Wnt-ß-catenin dependent anticancer therapy resistance in leukaemia stem cells. Nat Cell Biol. 2020 Jun; 22(6):689-700. PMID: 32313104.
      View in: PubMed
    2. Zhao M, Tao F, Venkatraman A, Li Z, Smith SE, Unruh J, Chen S, Ward C, Qian P, Perry JM, Marshall H, Wang J, He XC, Li L. N-Cadherin-Expressing Bone and Marrow Stromal Progenitor Cells Maintain Reserve Hematopoietic Stem Cells. Cell Rep. 2019 01 15; 26(3):652-669.e6. PMID: 30650358.
      View in: PubMed
    3. Li Z, Qian P, Shao W, Shi H, He XC, Gogol M, Yu Z, Wang Y, Qi M, Zhu Y, Perry JM, Zhang K, Tao F, Zhou K, Hu D, Han Y, Zhao C, Alexander R, Xu H, Chen S, Peak A, Hall K, Peterson M, Perera A, Haug JS, Parmely T, Li H, Shen B, Zeitlinger J, He C, Li L. Author Correction: Suppression of m6A reader Ythdf2 promotes hematopoietic stem cell expansion. Cell Res. 2018 10; 28(10):1042. PMID: 30150672.
      View in: PubMed
    4. Li Z, Qian P, Shao W, Shi H, He XC, Gogol M, Yu Z, Wang Y, Qi M, Zhu Y, Perry JM, Zhang K, Tao F, Zhou K, Hu D, Han Y, Zhao C, Alexander R, Xu H, Chen S, Peak A, Hall K, Peterson M, Perera A, Haug JS, Parmely T, Li H, Shen B, Zeitlinger J, He C, Li L. Suppression of m6A reader Ythdf2 promotes hematopoietic stem cell expansion. Cell Res. 2018 09; 28(9):904-917. PMID: 30065315.
      View in: PubMed
    5. Qian P, De Kumar B, He XC, Nolte C, Gogol M, Ahn Y, Chen S, Li Z, Xu H, Perry JM, Hu D, Tao F, Zhao M, Han Y, Hall K, Peak A, Paulson A, Zhao C, Venkatraman A, Box A, Perera A, Haug JS, Parmely T, Li H, Krumlauf R, Li L. Retinoid-Sensitive Epigenetic Regulation of the Hoxb Cluster Maintains Normal Hematopoiesis and Inhibits Leukemogenesis. Cell Stem Cell. 2018 05 03; 22(5):740-754.e7. PMID: 29727682.
      View in: PubMed
    6. Xu B, Li H, Perry JM, Singh VP, Unruh J, Yu Z, Zakari M, McDowell W, Li L, Gerton JL. Ribosomal DNA copy number loss and sequence variation in cancer. PLoS Genet. 2017 Jun; 13(6):e1006771. PMID: 28640831.
      View in: PubMed
    7. Qian P, He XC, Paulson A, Li Z, Tao F, Perry JM, Guo F, Zhao M, Zhi L, Venkatraman A, Haug JS, Parmely T, Li H, Dobrowsky RT, Ding WX, Kono T, Ferguson-Smith AC, Li L. The Dlk1-Gtl2 Locus Preserves LT-HSC Function by Inhibiting the PI3K-mTOR Pathway to Restrict Mitochondrial Metabolism. Cell Stem Cell. 2016 Feb 04; 18(2):214-28. PMID: 26627594.
      View in: PubMed
    8. Zhao M, Perry JM, Marshall H, Venkatraman A, Qian P, He XC, Ahamed J, Li L. Megakaryocytes maintain homeostatic quiescence and promote post-injury regeneration of hematopoietic stem cells. Nat Med. 2014 Nov; 20(11):1321-6. PMID: 25326798.
      View in: PubMed
    9. Venkatraman A, He XC, Thorvaldsen JL, Sugimura R, Perry JM, Tao F, Zhao M, Christenson MK, Sanchez R, Yu JY, Peng L, Haug JS, Paulson A, Li H, Zhong XB, Clemens TL, Bartolomei MS, Li L. Maternal imprinting at the H19-Igf2 locus maintains adult haematopoietic stem cell quiescence. Nature. 2013 Aug 15; 500(7462):345-9. PMID: 23863936.
      View in: PubMed
    10. Wang F, Scoville D, He XC, Mahe MM, Box A, Perry JM, Smith NR, Lei NY, Davies PS, Fuller MK, Haug JS, McClain M, Gracz AD, Ding S, Stelzner M, Dunn JC, Magness ST, Wong MH, Martin MG, Helmrath M, Li L. Isolation and characterization of intestinal stem cells based on surface marker combinations and colony-formation assay. Gastroenterology. 2013 Aug; 145(2):383-95.e1-21. PMID: 23644405.
      View in: PubMed
    11. Zhao M, Ross JT, Itkin T, Perry JM, Venkatraman A, Haug JS, Hembree MJ, Deng CX, Lapidot T, He XC, Li L. FGF signaling facilitates postinjury recovery of mouse hematopoietic system. Blood. 2012 Aug 30; 120(9):1831-42. PMID: 22802336.
      View in: PubMed
    12. Perry JM, Li L. To be or not to be a stem cell: dissection of cellular and molecular components of haematopoietic stem cell niches. EMBO J. 2012 Mar 07; 31(5):1060-1. PMID: 22327217.
      View in: PubMed
    13. Perry JM, He XC, Sugimura R, Grindley JC, Haug JS, Ding S, Li L. Cooperation between both Wnt/{beta}-catenin and PTEN/PI3K/Akt signaling promotes primitive hematopoietic stem cell self-renewal and expansion. Genes Dev. 2011 Sep 15; 25(18):1928-42. PMID: 21890648.
      View in: PubMed
    14. Arnold CP, Tan R, Zhou B, Yue SB, Schaffert S, Biggs JR, Doyonnas R, Lo MC, Perry JM, Renault VM, Sacco A, Somervaille T, Viatour P, Brunet A, Cleary ML, Li L, Sage J, Zhang DE, Blau HM, Chen C, Chen CZ. MicroRNA programs in normal and aberrant stem and progenitor cells. Genome Res. 2011 May; 21(5):798-810. PMID: 21451113.
      View in: PubMed
    15. Perry JM, Li L. Functional assays for hematopoietic stem cell self-renewal. Methods Mol Biol. 2010; 636:45-54. PMID: 20336515.
      View in: PubMed
    16. Perry JM, Harandi OF, Porayette P, Hegde S, Kannan AK, Paulson RF. Maintenance of the BMP4-dependent stress erythropoiesis pathway in the murine spleen requires hedgehog signaling. Blood. 2009 Jan 22; 113(4):911-8. PMID: 18927434.
      View in: PubMed
    17. Perry JM, Li L. Self-renewal versus transformation: Fbxw7 deletion leads to stem cell activation and leukemogenesis. Genes Dev. 2008 May 01; 22(9):1107-9. PMID: 18451101.
      View in: PubMed
    18. Haug JS, He XC, Grindley JC, Wunderlich JP, Gaudenz K, Ross JT, Paulson A, Wagner KP, Xie Y, Zhu R, Yin T, Perry JM, Hembree MJ, Redenbaugh EP, Radice GL, Seidel C, Li L. N-cadherin expression level distinguishes reserved versus primed states of hematopoietic stem cells. Cell Stem Cell. 2008 Apr 10; 2(4):367-79. PMID: 18397756.
      View in: PubMed
    19. Hegde S, Lenox LE, Lariviere A, Porayette P, Perry JM, Yon M, Paulson RF. An intronic sequence mutated in flexed-tail mice regulates splicing of Smad5. Mamm Genome. 2007 Dec; 18(12):852-60. PMID: 18060457.
      View in: PubMed
    20. Perry JM, Li L. Disrupting the stem cell niche: good seeds in bad soil. Cell. 2007 Jun 15; 129(6):1045-7. PMID: 17574018.
      View in: PubMed
    21. Perry JM, Harandi OF, Paulson RF. BMP4, SCF, and hypoxia cooperatively regulate the expansion of murine stress erythroid progenitors. Blood. 2007 May 15; 109(10):4494-502. PMID: 17284534.
      View in: PubMed
    22. Lenox LE, Perry JM, Paulson RF. BMP4 and Madh5 regulate the erythroid response to acute anemia. Blood. 2005 Apr 01; 105(7):2741-8. PMID: 15591122.
      View in: PubMed
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