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KATHERINE YUDEH KING

TitleAssistant Professor
InstitutionBaylor College of Medicine
DepartmentDepartment of Pediatrics
DivisionPediatrics-Infectious Diseases
AddressONE BAYLOR PLAZA
HOUSTON TX 77030
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    Collapse Biography 
    Collapse awards and honors
    2015 - 2017Liviya Anderson Research Award, Aplastic Anemia and MDS International Foundation
    2015 - 2017Basil O'Connor Starter Scholar Award, March of Dimes
    2014 - 2015BCM Junior Faculty Seed Grant, Caroline Wiess Law Fund for Research in Molecular Medicine
    2010 - 2015KO8 Mentored Clinical Scientist Training Award, NIH
    2011 - 2012Pediatric Pilot Award, Texas Children's Hospital
    2008 - 2009Collaborative Research Grant, L.E. and Virginia Simmons Family Foundation

    Collapse Overview 
    Collapse overview
    Bone marrow suppression and pancytopenia can result from chronic inflammation. Bone marrow suppression is a risk factor for increased mortality for patients with chronic infections and aplastic anemia. However, very little is known about the mechanisms by which inflammatory cytokines affect the hematopoietic progenitors that reside in bone marrow. We discovered that interferon gamma (IFNg) promotes hematopoietic stem cell (HSC) division and myeloid differentiation in a mouse model of Mycobacterium avium infection. While this response can be helpful in the short term, it may be deleterious over the long term, with prolonged inflammation leading to stem cell exhaustion.

    Work in our laboratory is focused on identifying the mechanisms by which the inflammatory cytokine IFNg affects proliferation, differentiation, and mobilization of HSCs. This knowledge is a key to understanding the pathophysiology of bone marrow failure syndromes and will likely provide novel targets for drug development. Furthermore, this work may elucidate how cancer stem cells respond to immunotherapies, as well as how infections can contribute to aging and oncogenesis.

    We have previously demonstrated that interferons, a class of inflammatory cytokines, directly activate hematopoietic stem cells (HSCs) to divide (Nature 2010). HSCs are the precursors of all cells of the peripheral blood, and they usually reside in a quiescent state in the bone marrow. Our work is among the first to demonstrate that inflammatory signaling can directly activate HSCs. Impaired quiescence mechanisms during long-term interferon stimulation result in differentiation and exhaustion of the HSC pool (Blood 2011, Stem Cells 2014). Such immune-mediated HSC exhaustion may contribute to peripheral cytopenias as seen in some chronic infections, post-infectious syndromes, and acquired aplastic anemia.

    Current projects in the lab include:

    Mediators of interferon-dependent HSC proliferation and differentiation. We conducted transcriptional profiling of HSCs from naïve and infected animals to identify molecular mediators of the HSC immune response. Currently we are characterizing candidate genes from that screen for their role in HSC quiescence and differentiation.

    Investigating the effects of IFNa treatment on human hematopoietic progenitors in polycythemia vera and acquired aplastic anemia. We are enrolling patients in two protocols to understand the role of interferon signaling in clonal replacement and/or suppression of HSCs in myeloproliferative neoplasms (polycythemia vera and essential thrombocythemia) as well as acquired aplastic anemia. We utilize molecular techniques to understand effects of interferon on regulation of HSC cell division, apoptosis, and differentiation.

    Collapse keywords
    hematopoiesis
    hematopoietic stem cell
    infectious diseases
    mycobacteria
    aplastic anemia
    bone marrow suppression
    interferon
    innate immunity


    Collapse Bibliographic 
    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. Matatall KA, Jeong M, Chen S, Sun D, Chen F, Mo Q, Kimmel M, King KY. Chronic Infection Depletes Hematopoietic Stem Cells through Stress-Induced Terminal Differentiation. Cell Rep. 2016 Dec 06; 17(10):2584-2595. PMID: 27926863.
      View in: PubMed
    2. Josefsdottir KS, Baldridge MT, Kadmon CS, King KY. Antibiotics impair murine hematopoiesis by depleting intestinal microbiota. Blood. 2016 Nov 22. PMID: 27879260.
      View in: PubMed
    3. Luis TC, Tremblay CS, Manz MG, North TE, King KY, Challen GA. Inflammatory signals in HSPC development and homeostasis: Too much of a good thing? Exp Hematol. 2016 Oct; 44(10):908-12. PMID: 27423816.
      View in: PubMed
    4. Li HS, Jin J, Liang X, Matatall KA, Ma Y, Zhang H, Ullrich SE, King KY, Sun SC, Watowich SS. Loss of c-Kit and bone marrow failure upon conditional removal of the GATA-2 C-terminal zinc finger domain in adult mice. Eur J Haematol. 2016 Sep; 97(3):261-70. PMID: 26660446.
      View in: PubMed
    5. King KY, Matatall KA, Shen CC, Goodell MA, Swierczek SI, Prchal JT. Comparative long-term effects of interferon ? and hydroxyurea on human hematopoietic progenitor cells. Exp Hematol. 2015 Oct; 43(10):912-918.e2. PMID: 26072330.
      View in: PubMed
    6. King KY, Hicks MJ, Mazziotti MV, Eldin KW, Starke JR, Michael M. Persistent cat scratch disease requiring surgical excision in a patient with MPGN. Pediatrics. 2015 Jun; 135(6):e1514-7. PMID: 25963015.
      View in: PubMed
    7. Josefsdottir KS, King KY. Interferons coordinate a multifaceted defense. Cell Host Microbe. 2015 Jan 14; 17(1):6-7. PMID: 25590754.
      View in: PubMed
    8. Trompouki E, King KY, Will B, Lessard J, Flores-Figueroa E, Kokkaliaris KD, Bowman T. Bloody signals: from birth to disease and death. Exp Hematol. 2014 Dec; 42(12):989-94. PMID: 25482344.
      View in: PubMed
    9. Matatall KA, Shen CC, Challen GA, King KY. Type II interferon promotes differentiation of myeloid-biased hematopoietic stem cells. Stem Cells. 2014 Nov; 32(11):3023-30. PMID: 25078851; PMCID: PMC4198460.
    10. Rodgers JT, King KY, Brett JO, Cromie MJ, Charville GW, Maguire KK, Brunson C, Mastey N, Liu L, Tsai CR, Goodell MA, Rando TA. mTORC1 controls the adaptive transition of quiescent stem cells from G0 to G(Alert). Nature. 2014 Jun 19; 510(7505):393-6. PMID: 24870234; PMCID: PMC4065227.
    11. Rossi L, Lin KK, Boles NC, Yang L, King KY, Jeong M, Mayle A, Goodell MA. Less is more: unveiling the functional core of hematopoietic stem cells through knockout mice. Cell Stem Cell. 2012 Sep 7; 11(3):302-17. PMID: 22958929; PMCID: PMC3461270.
    12. King KY, Goodell MA. Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response. Nat Rev Immunol. 2011 Oct; 11(10):685-92. PMID: 21904387; PMCID: PMC4154310.
    13. King KY, Baldridge MT, Weksberg DC, Chambers SM, Lukov GL, Wu S, Boles NC, Jung SY, Qin J, Liu D, Songyang Z, Eissa NT, Taylor GA, Goodell MA. Irgm1 protects hematopoietic stem cells by negative regulation of IFN signaling. Blood. 2011 Aug 11; 118(6):1525-33. PMID: 21633090; PMCID: PMC3156044.
    14. King KY, Goodell MA. Direct conversion of skin cells into blood: alchemy or science? Mol Ther. 2011 Feb; 19(2):227-8. PMID: 21289635; PMCID: PMC3034862.
    15. King KY, Lew JD, Ha NP, Lin JS, Ma X, Graviss EA, Goodell MA. Polymorphic allele of human IRGM1 is associated with susceptibility to tuberculosis in African Americans. PLoS One. 2011; 6(1):e16317. PMID: 21283700; PMCID: PMC3025014.
    16. Baldridge MT, King KY, Goodell MA. Inflammatory signals regulate hematopoietic stem cells. Trends Immunol. 2011 Feb; 32(2):57-65. PMID: 21233016; PMCID: PMC3042730.
    17. Baldridge MT, King KY, Boles NC, Weksberg DC, Goodell MA. Quiescent haematopoietic stem cells are activated by IFN-gamma in response to chronic infection. Nature. 2010 Jun 10; 465(7299):793-7. PMID: 20535209; PMCID: PMC2935898.
    18. King KY, Edwards MS, Word BM. Hepatitis associated with micafungin use in a preterm infant. J Perinatol. 2009 Apr; 29(4):320-2. PMID: 19325554.
      View in: PubMed
    19. King K, Browning JC, Metry DW, Prestigiacomo J, Scollard D, Schutze GE, Stryjewska B, Schwarzwald H. Leprosy and international adoption: a case report and review of diagnostic and treatment dilemmas. Pediatr Infect Dis J. 2009 Apr; 28(4):322-5. PMID: 19238115.
      View in: PubMed
    20. Brenot A, King KY, Caparon MG. The PerR regulon in peroxide resistance and virulence of Streptococcus pyogenes. Mol Microbiol. 2005 Jan; 55(1):221-34. PMID: 15612930.
      View in: PubMed
    21. Brenot A, King KY, Janowiak B, Griffith O, Caparon MG. Contribution of glutathione peroxidase to the virulence of Streptococcus pyogenes. Infect Immun. 2004 Jan; 72(1):408-13. PMID: 14688122; PMCID: PMC344014.
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