Ya-Huei Kuo, Ph.D.

(626) 256-4673
Ya-Huei Kuo, Ph.D.
Professor, Department of Hematologic Malignancies Translational Science
Research Area
  • Acute Myeloid Leukemia
  • Development of Targeted Therapy
  • Genetic Mouse Models
  • Hematology and Hematopoietic Cell Transplantation
  • Hematologic Malignancies
  • Leukemia Stem Cells
  • Stem Cell Biology
  • Mathematical Oncology
  • Preclinical Studies
As a key researcher in the Department of Hematologic Malignancies Translational Science within Beckman Research Institute of City of Hope®, Ya-Huei Kuo, PH.D., runs a laboratory focused on understanding the molecular anatomy of leukemia stem cells, and developing novel methods for targeting and attacking them. She has published dozens of scholarly papers and received the 2012 American Cancer Society Research Scholar Grant Award.
 
Dr. Kuo joined City of Hope in 2008 after a fellowship in genetics, hematology and cancer biology at University of Massachusetts Medical School.

Location

Education & Experience

Degrees

  • 2001, Ph.D., Cell Biology, University of Connecticut, Storrs, Connecticut
  • 1995, B.S., Zoology, National Taiwan University, Taipei

Fellowship

  • 2002-2007, Postdoctoral fellow, Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts

Professional Experience

  • 2024–present, Professor, Department of Hematological Malignancies Translational Science, Beckman Research Institute of City of Hope, Duarte, California
  • 2017–2024, Associate Professor, Department of Hematological Malignancies Translational Science, Norbert Gehr and Family Leukemia Center, Beckman Research Institute of City of Hope, Duarte, California
  • 2014–2017, Associate Professor, Division of Hematopoietic Stem Cell and Leukemia Research, Gehr Family Center for Leukemia Research, Beckman Research Institute, City of Hope, Duarte, California
  • 2008–present, Program Member, City of Hope Comprehensive Cancer Center, Duarte, California
  • 2008–2014, Assistant Professor, Hematology & Hematopoietic Cell Transplantation and Leukemia Research, Beckman Research Institute, City of Hope, Duarte, California
  • 2002–2007, Postdoctoral Fellow, Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts. Mentor: Lucio H. Castilla, Ph.D.
  • 1996–2001, Predoctoral Fellow, University of Connecticut, Storrs, Connecticut, Dissertation: A study on the novel activities of pro-IGF-I E-peptides in human neuroblastoma cells. Mentor: Thomas T. Chen, Ph.D.
  • 1997–1999, Teaching Assistant, Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut, Course: Introductory Biology Laboratory, Cell Biology
  • 1995–1996, Research Assistant, Hepatitis Research Center, School of Medicine, National Taiwan University, Taipei, Taiwan. Advisor: Ming-Yang Lai, M.D., Ph.D.
  • 1994–1995, Research Intern, Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan. Advisor: Huai-Jen Tsai, Ph.D.

Research

Molecular Genetics of Hematopoietic Stem Cells and Leukemia Stem Cells

Acute myeloid leukemia (AML) is the most common type of leukemia in adults with approximately 20,000 new cases and 10,000 deaths each year in the United States. Despite considerable improvement of survival rates for patients with leukemia over the past 50 years, the overall five-year relative survival rate for AML patients is only approximately 20%.

Leukemia stem cells (LSCs) are now recognized as the critical “seeds” of leukemia, and represent a fundamental challenge thought to underlie poor outcome due to their relative resistance to standard chemotherapy. Our long-term goal is to elucidate the molecular mechanism(s) regulating the maintenance of LSCs, to understand how they differ from normal hematopoietic stem cells, and to develop novel LSC-targeted therapeutics. Using a genetic mouse model of a common chromosome aberration found in AML patients, known as inv(16), we have shown that leukemia arises as a result of a multistep transformation process involving mutations that disrupt hematopoietic differentiation, and those that deregulate proliferation and self-renewal programs.

Our current research efforts are directed towards understanding the molecular pathways and functional mediators regulating normal hematopoiesis as well as those underlying leukemogenesis using a combination of genetics, genomics, biochemistry, proteomics, molecular biology and cellular biology approaches. We use defined genetic mouse models as an experimental system to identify molecular pathways and targets, and primary cells from AML patients to validate the findings and perform further translational and preclinical studies. We believe that a comprehensive understanding of oncogenic mechanisms will enable rational design and selection of improved cancer treatments.

Awards & Memberships

Awards

  • 2012-2016, American Cancer Society Research Scholar Award

  • 2010-2012, Concern Foundation CONquer canCER Now Award

  • 2009-2012, The V Foundation for Cancer Research, V Scholar Award

  • 2009, Lauri Strauss Leukemia Foundation Discovery Research Grant Award

  • 2009-2011, Margaret E. Early Medical Research Award

  • 2008-2011, STOP CANCER Research Career Development Award

  • 2004-2007, Individual Postdoctoral Fellowship, Ruth L. Kirschstein National Research Service Award, National Cancer Institute, National Institutes of Health

  • 2003-2004, Postdoctoral Fellowship, Our Danny Cancer Fund, Cancer Center, University of Massachusetts Medical School

Memberships

  • 2020-present, NCI Physical Science-oncology Network (PS-ON) Steering Committee
  • 2008-present, American Society of Hematology (ASH)
  • 2016-present, International Society of Experimental Hematology (ISEH)
  • 2014-present, American Association of Cancer Research (AACR)
  • 1998-2003, American Society for Cell Biology (ASCB)

Publications

  • Jeannet R, Cai Q, Liu H, Vu H, Kuo YH. (2013) Alcam regulates long-term hematopoietic stem cell engraftment and self-renewal. Stem Cells 31(3): 560-71. PMID: 23280653; PMCID: PMC3832064.
  • Dos Santos C. McDonald T, Ho YW, Liu H, Lin A, Forman SJ, Kuo YH*, and Bhatia R*. (2013) The Src and c-Kit kinase inhibitor dasatinib enhances p53-mediated targeting of human acute myeloid leukemia stem cell by chemotherapeutic agents. Blood 122(11): 1900-13. PMID: 23896410. (* Equal contribution, co-correspondence) 
  • Hossain DM, Dos Santos C, Zhang Q, Kozlowska A, Liu H, Gao C, Moreira D, Swiderski P, Jozwiak A, Kline J, Forman S, Bhatia R, Kuo YH*, and Kortylewski M*. (2014) Leukemia cell-targeted STAT3 silencing and TLR-9-triggering generate systemic antitumor immunity. Blood 123(1): 15-25. PMID: 24169824; PMCID: PMC3879904. (* Equal contribution, co-correspondence)
  • Qi J, Singh S, Hua WK, Cai Q, Chao S-W, Li L, Liu H, Ho Y, McDonald T, Lin A, Marcucci G, Bhatia R, Huang W-J, Chang C-I, Kuo YH. (2015) HDAC8 inhibition specifically targets inv(16) acute myeloid leukemia stem cells by restoring p53 acetylation. Cell Stem Cell 17:5, 597-610, PMID: 26387755; PMCID: PMC4636961. (Cover)
  • Cai Q, Jeannet R, Hua WK, Cook GJ, Zhang B, Qi J, Liu H, Li L, Chen, CC, Marcucci G and Kuo YH. (2016) CBFβ-SMMHC creates aberrant megakaryocyte-erythroid progenitors prone to leukemia-initiation in mice. Blood 128(11): 1503-15. PMID: 27443289; PMCID: PMC5025900.
  • Hua WK, Qi J, Cai Q, Carnahan E, Li L, Marcucci G, and Kuo YH. (2017) HDAC8 regulates long-term hematopoietic stem cell maintenance under stress by modulating p53 activity. Blood. 130(24):2619-2630. PMID: 29084772; PMCID: PMC5731083.
  • Zhang B, Nguyen LXT, Li L, Zhao D, Kumar B, Wu H, Lin A, Pellicano F, Hopcroft L, Su YL, Copland M, Holyoake TL, Kuo CJ, Bhatia R, Snyder DS, Ali H, Stein AS, Brewer C, Wang H, McDonald T, Swiderski P, Troadec E, Chen CC, Dorrance A, Pullarkat V, Yuan YC, Perrotti D, Carlesso N, Forman SJ, Kortylewski M*, Kuo YH*, Marcucci G*. (2018) Bone Marrow Niche Trafficking of miR-126 Controls Self-Renewal of Leukemia Stem Cells in Chronic Myelogenous Leukemia. Nature Medicine 24(4):450-462 PMID: 29505034. (*equal contribution)
  • Rockne RC*, Branciamore S, Qi J, Frankhouser DE, O'Meally D, Hua WK, Cook G, Carnahan E, Zhang L, Marom A, Wu H, Maestrini D, Wu X, Yuan YC, Liu Z, Wang LD, Forman S, Carlesso N, Kuo YH*††, Marcucci G+††. (2020) State-transition Analysis of Time-Sequential Gene Expression Identifies Critical Points That Predict Development of Acute Myeloid Leukemia. (*correspondence; ††equal contribution) Cancer Res. 2020 Aug 1;80(15):3157-3169. doi: 10.1158/0008-5472.CAN-20-0354. PMID: 32414754; PMCID: PMC7416495.
  • Zhang L, Nguyen LXT, Chen YC, Wu D, Cook GJ, Hoang DH, Brewer CJ, He X, Dong H, Li S, Li M, Zhao D, Qi J, Hua WK, Cai Q, Carnahan E, Chen W, Wu X, Swiderski P, Rockne RC, Kortylewski M, Li L, Zhang B, Marcucci G, Kuo YH. Targeting miR-126 in inv(16) acute myeloid leukemia inhibits leukemia development and leukemia stem cell maintenance. Nat Commun. 2021 Oct 22;12(1):6154. doi: 10.1038/s41467-021-26420-7. PubMed PMID: 34686664; PubMed Central PMCID: PMC8536759.

  • Frankhouser DE, O'Meally D, Branciamore S, Uechi L, Zhang L, Chen YC, Li M, Qin H, Wu X, Carlesso N, Marcucci G, Rockne RC, Kuo YH. Dynamic patterns of microRNA expression during acute myeloid leukemia state-transition. Sci Adv. 2022 Apr 22;8(16):eabj1664. doi: 10.1126/sciadv.abj1664. PMID: 35452289; PMCID: PMC9032952. (*correspondence)


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