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Taeju Park, PhD

TitleResearch Faculty PhD
InstitutionChildren's Mercy Kansas City
DepartmentPediatrics
Address2401 Gillham Rd
Kansas City MO 64108
ORCID ORCID Icon0000-0003-3897-3994 Additional info
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    Other Positions
    TitleAssistant Professor of Pediatrics
    InstitutionUniversity of Missouri-Kansas City
    DepartmentPediatrics


    Collapse Biography 
    Collapse education and training
    Pohang University of Science and technology, Pohang, KoreaPhD02/1999Biochemistry and Molecular Biology
    RIKEN Brain Science Institute, Wako, JapanFellowship02/2002Signal Transduction
    Pohang University of Science and technology, Pohang, KoreaFellowship09/2002Biochemistry and Molecular Biology
    St. Jude Children’s Research Hospital, Memphis, USAFellowship06/2006Mouse Genetics and Neuroscience
    Collapse awards and honors
    2008 - 2009Alavi-Dabiri Postdoctoral Fellowship Award, Children’s Hospital of Philadelphia

    Collapse Overview 

    Collapse Research 
    Collapse research overview
    Dr. Park’s study is focused on two proteins – Crk and CrkL – that are reported to be elevated in several types of human cancer including glioblastoma (GBM) and correlated with poor prognosis. Tumor cell migration and invasion contribute to the spread of GBM to healthy brain tissues, leading to high recurrence rates. Dr. Park has demonstrated that Crk and CrkL play important roles in GBM cell migration and invasion. Dr. Park is also working on potential role of Crk and CrkL in diffuse intrinsic pontine glioma (DIPG) cell migration and invasion. In addition, Dr. Park is working to develop specific inhibitors of these proteins to block GBM cell migration and invasion.

    In the lab, he and his team take advantage of genetically engineered mouse models and the gene knockdown technique to study tumorigenic functions of Crk and CrkL. They identified a protein that is activated by elevation of Crk and CrkL and binds to Crk and CrkL. The new malignant
    connection promotes tumor cell migration and invasion. Dr. Park’s goal is to develop drugs that specifically break down the aberrant protein-protein complex between Crk and CrkL and their binding partners. To test effects of chemical compounds on the binding of these proteins, Dr. Park developed in vitro assay systems and conducted a high-throughput screen. In partnership with the University of Kansas Cancer Center, the team has tested 200,000 chemical compounds and identified more than 600 potential candidate drugs. These compounds are undergoing rigorous post-screening validation using different biochemical experiments. We will continue to expand productive collaboration with KU core facilities to discover novel anticancer drugs. We are optimizing a new quadruple screening to discover inhibitors of both SH2 and SH3 domains of Crk and CrkL. The newly developed inhibitors will be used to advance studies of cancer and other human diseases in which Crk and CrkL play essential roles.
    Collapse research activities and funding
    SAP#4100047628     (Tom Curran)Jan 1, 2009 - Dec 31, 2012
    Pennsylvania Department of Health Cure Formulary grant
    "Role of Crk and CrkL in Normal and Neoplastic Growth"
    Role Description: Understanding the specific biological functions of Crk and CrkL has been challenging because deletion of either gene from the mouse germline results in embryonic or early postnatal lethality, and because both proteins function very similarly in biochemical and molecular assays. Previously, we generated mutant mice carrying floxed alleles of Crk and CrkL allowing conditional mutation using the CRE system. Ablation of both Crk and CrkL in neuronal precursor cells demonstrated that they provide specific overlapping functions downstream of Reelin in the control of radial neuronal migration during brain development. This project represents an expansion and new direction of this study to investigate the role of Crk and CrkL in a range of cell types in vitro and in vivo. Establishment of the Crkfl/fl/CrkLfl/fl strain of mice as well as Crkfl/fl and CrkLfl/fl strains provides a unique and powerful experimental tool. Three specific aims were addressed that focus on the role of Crk and CrkL in fibroblast growth (Aim 1), in other cell types in vivo and in vivo (Aim 2) and in cell transformation and tumor growth (Aim 3). Comparison of phenotypes obtained from Crkfl/fl/CrkLfl/fl cells and tissues with those from Crkfl/fl and CrkLfl/fl mice provided detailed understanding of how Crk and CrkL play both overlapping and individually unique functions in various cells and tissues. Understanding both conserved and specific functions of Crk and CrkL in various cell types will enable us to address fundamental questions in birth defects and cancer.
    Role: Key Personnel

    500847     (Taeju Park)Oct 1, 2017 - Sep 30, 2019
    Tom Keaveny Endowed Fund
    "Requirement of CT10 regulator of kinase (Crk) and Crk-like (CrkL) in glioblastoma growth"
    Role Description: The long-term objective of our research is to develop specific inhibitors of Crk and CrkL for glioblastoma (GBM) treatment. As an important step toward developing a novel therapy for GBM, this project aimed at obtaining key in vitro data to address the feasibility of Crk and CrkL as therapeutic targets. In the proposed research, human GBM cell lines were used to test whether Crk and CrkL are required for GBM cell growth and migration. We compared commercially available small interfering RNAs (siRNAs) to identify specific and potent suppressors of Crk and CrkL expression using a human glioblastoma cell line. Using these siRNAs, we induced single and double knockdowns of Crk and CrkL in a glioblastoma cell line to analyze quantitatively the resulting cellular phenotypes. Our findings elaborate the predominant role of CrkL and the essential overlapping functions of Crk and CrkL in glioblastoma cell structure, growth, adhesion, migration, and invasion. Our study indicates that cell migration is a specific, measurable, cellular outcome that requires both Crk and CrkL, thus providing a pathway for translational exploration.
    Role: PI

         (Taeju Park)Nov 1, 2017 - Jun 30, 2020
    Children's Mercy Hospital Midwest Cancer Alliance Partner Advisory Board Funding
    "Development of CT10 regulator of kinase (Crk) and Crk-like (CrkL) inhibitors for glioblastoma treatment"
    Role Description: As the first essential step toward a novel therapy for GBM, the goal of this proposed project was to discover compounds that specifically inhibit functions of Crk and CrkL. High throughput screening of chemical libraries and validation of hit compounds required close collaboration with the University of Kansas High Throughput Screening Laboratory (KU-HTSL), which provided technical expertise, instrumentation, and personnel for optimization of the fluorescence polarization-based binding assay, high throughput screening, and biochemical validation. Fluorescence polarization assays for screening system establishment, library screening, and the initial biochemical validation were conducted in the KU-HTSL. Molecular cloning, protein purification, and cell-based validations were carried out at Children’s Mercy. We identified several lead compounds for drug development and evaluated the lead compounds using cell-based and biochemical assays.
    Role: PI

         (Taeju Park)Oct 1, 2019 - Sep 30, 2021
    Katharine Berry Richardson Foundation (KBR) grant
    "Requirement of the Crk/CrkL in Cancer Cell Migration and Invasion"
    Role Description: In the proposed research, we will conduct critical in vitro studies to test whether the interaction between Crk/CrkL and p130Cas is required for accelerated tumor cell migration and invasion caused by overexpression of Crk, CrkL, and p130Cas. Human GBM cell lines will be used to determine whether the Crk/CrkL-p130Cas interaction is critical in GBM cell migration and invasion and to further demonstrate that the Crk-p130Cas axis is a promising therapeutic target for cancer treatment.
    Role: PI

         (Taeju Park)Nov 1, 2020 - Dec 31, 2022
    Children's Mercy Hospital Masonic Cancer Alliance Partner Advisory Board Funding
    "Advanced development of Crk and CrkL inhibitors for glioblastoma treatment (renewal)"
    Role Description: The prior MCA PAB funding enabled us to establish various biochemical and cell-based assays for screening and validation and to conduct high throughput screening and extensive post-screening validation in collaboration with the University of Kansas High Throughput Screening Laboratory (KU-HTSL). The prior research also highlighted the need to redesign the screening system to streamline the drug development process and widen the target range. The various assays that we established and in-depth scientific knowledge and insights we obtained in the prior research will help us accelerate the drug development process in the proposed research. We will continue to expand productive collaboration with KU core facilities to discover novel anticancer drugs. We are optimizing a new quadruple screening to discover inhibitors of both SH2 and SH3 domains of Crk and CrkL. The newly developed inhibitors will be used to advance studies of cancer and other human diseases in which Crk and CrkL play essential roles.
    Role: PI

         (Taeju Park)Dec 7, 2020
    Natalie's ART Foundation
    "Role of Crk and CrkL in diffuse intrinsic potine glioma (DIPG) cell migration and invasion"
    Role Description: Diffuse intrinsic pontine glioma (DIPG)or diffuse midline glioma (DMG) is a highly malignant tumor in the brain stem and primarily affects children. There is no cure for this tumor, and the survival rate is very low. Due to the tumor’s location, surgical resection of tumor is extremely difficult, and no effective chemotherapy drug is available. Recently, overexpression of Crk was reported in DIPG patients. In this study, patient-derived DIPG cell lines will be used to study roles of Crk and CrkL in DIPG cell growth, migration, and invasion. Genetically manipulating the expression levels of Crk and CrkL protein in DIPG cell lines and comparing the results with those obtained from GBM cells would provide novel insights into the therapeutic intervention of DIPG.
    Role: PI

    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. Park T. Crk and CrkL as Therapeutic Targets for Cancer Treatment. Cells. 2021 Mar 27; 10(4). PMID: 33801580.
      View in: PubMed
    2. Park T, Large N, Curran T. Quantitative assessment of glioblastoma phenotypes in vitro establishes cell migration as a robust readout of Crk and CrkL activity. J Biol Chem. 2021 Feb 06; 100390. PMID: 33561443.
      View in: PubMed
    3. Park T, Curran T. Requirement for Crk and CrkL during postnatal lens development. Biochem Biophys Res Commun. 2020 08 27; 529(3):603-607. PMID: 32736680.
      View in: PubMed
    4. Mudduluru G, Large N, Park T. Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion. J Vis Exp. 2020 04 02; (158). PMID: 32310229.
      View in: PubMed
    5. Nabekura T, Chen Z, Schroeder C, Park T, Vivier E, Lanier LL, Liu D. Crk Adaptor Proteins Regulate NK Cell Expansion and Differentiation during Mouse Cytomegalovirus Infection. J Immunol. 2018 05 15; 200(10):3420-3428. PMID: 29618525.
      View in: PubMed
    6. Collins TN, Mao Y, Li H, Bouaziz M, Hong A, Feng GS, Wang F, Quilliam LA, Chen L, Park T, Curran T, Zhang X. Crk proteins transduce FGF signaling to promote lens fiber cell elongation. Elife. 2018 01 23; 7. PMID: 29360039.
      View in: PubMed
    7. Park T, Koptyra M, Curran T. Fibroblast Growth Requires CT10 Regulator of Kinase (Crk) and Crk-like (CrkL). J Biol Chem. 2016 Dec 16; 291(51):26273-26290. PMID: 27807028.
      View in: PubMed
    8. Huang Y, Clarke F, Karimi M, Roy NH, Williamson EK, Okumura M, Mochizuki K, Chen EJ, Park TJ, Debes GF, Zhang Y, Curran T, Kambayashi T, Burkhardt JK. CRK proteins selectively regulate T cell migration into inflamed tissues. J Clin Invest. 2015 Mar 02; 125(3):1019-32. PMID: 25621495.
      View in: PubMed
    9. Koptyra M, Park TJ, Curran T. Crk and CrkL are required for cell transformation by v-fos and v-ras. Mol Carcinog. 2016 Jan; 55(1):97-104. PMID: 25557916.
      View in: PubMed
    10. Park TJ, Curran T. Neurobiology: Reelin mediates form and function. Curr Biol. 2014 Nov 17; 24(22):R1089-92. PMID: 25458219.
      View in: PubMed
    11. Kim J, Park TJ, Kwon N, Lee D, Kim S, Kohmura Y, Ishikawa T, Kim KT, Curran T, Je JH. Dendritic planarity of Purkinje cells is independent of Reelin signaling. Brain Struct Funct. 2015 Jul; 220(4):2263-73. PMID: 24828132.
      View in: PubMed
    12. George B, Fan Q, Dlugos CP, Soofi AA, Zhang J, Verma R, Park TJ, Wong H, Curran T, Nihalani D, Holzman LB. Crk1/2 and CrkL form a hetero-oligomer and functionally complement each other during podocyte morphogenesis. Kidney Int. 2014 Jun; 85(6):1382-1394. PMID: 24499776.
      View in: PubMed
    13. Park TJ, Curran T. Essential roles of Crk and CrkL in fibroblast structure and motility. Oncogene. 2014 Oct 23; 33(43):5121-32. PMID: 24166500.
      View in: PubMed
    14. George B, Verma R, Soofi AA, Garg P, Zhang J, Park TJ, Giardino L, Ryzhova L, Johnstone DB, Wong H, Nihalani D, Salant DJ, Hanks SK, Curran T, Rastaldi MP, Holzman LB. Crk1/2-dependent signaling is necessary for podocyte foot process spreading in mouse models of glomerular disease. J Clin Invest. 2012 Feb; 122(2):674-92. PMID: 22251701.
      View in: PubMed
    15. Austgen K, Johnson ET, Park TJ, Curran T, Oakes SA. The adaptor protein CRK is a pro-apoptotic transducer of endoplasmic reticulum stress. Nat Cell Biol. 2011 Dec 18; 14(1):87-92. PMID: 22179045.
      View in: PubMed
    16. Hallock PT, Xu CF, Park TJ, Neubert TA, Curran T, Burden SJ. Dok-7 regulates neuromuscular synapse formation by recruiting Crk and Crk-L. Genes Dev. 2010 Nov 01; 24(21):2451-61. PMID: 21041412.
      View in: PubMed
    17. Park TJ, Curran T. Alternative splicing disabled by Nova2. Neuron. 2010 Jun 24; 66(6):811-3. PMID: 20620865.
      View in: PubMed
    18. Park TJ, Curran T. Crk and Crk-like play essential overlapping roles downstream of disabled-1 in the Reelin pathway. J Neurosci. 2008 Dec 10; 28(50):13551-62. PMID: 19074029.
      View in: PubMed
    19. Park TJ, Boyd K, Curran T. Cardiovascular and craniofacial defects in Crk-null mice. Mol Cell Biol. 2006 Aug; 26(16):6272-82. PMID: 16880535.
      View in: PubMed
    20. Choi BH, Chae HD, Park TJ, Oh J, Lim J, Kang SS, Ha H, Kim KT. Protein kinase C regulates the activity and stability of serotonin N-acetyltransferase. J Neurochem. 2004 Jul; 90(2):442-54. PMID: 15228600.
      View in: PubMed
    21. Park TJ, Kim KT. Activation of B2 bradykinin receptors by neurotensin. Cell Signal. 2003 May; 15(5):519-27. PMID: 12639715.
      View in: PubMed
    22. Park TJ, Hamanaka H, Ohshima T, Watanabe N, Mikoshiba K, Nukina N. Inhibition of ubiquitin ligase Siah-1A by disabled-1. Biochem Biophys Res Commun. 2003 Mar 21; 302(4):671-8. PMID: 12646221.
      View in: PubMed
    23. Park TJ, Park YS, Lee TG, Ha H, Kim KT. Inhibition of acetylcholine-mediated effects by borneol. Biochem Pharmacol. 2003 Jan 01; 65(1):83-90. PMID: 12473382.
      View in: PubMed
    24. Hur EM, Park TJ, Kim KT. Coupling of L-type voltage-sensitive calcium channels to P2X(2) purinoceptors in PC-12 cells. . 2001 May; 280(5):C1121-9. PMID: 11287325.
      View in: PubMed
    25. Park T, Bae S, Choi S, Kang B, Kim K. Inhibition of nicotinic acetylcholine receptors and calcium channels by clozapine in bovine adrenal chromaffin cells. Biochem Pharmacol. 2001 Apr 15; 61(8):1011-9. PMID: 11286992.
      View in: PubMed
    26. Park TJ, Seo HK, Kang BJ, Kim KT. Noncompetitive inhibition by camphor of nicotinic acetylcholine receptors. Biochem Pharmacol. 2001 Apr 01; 61(7):787-93. PMID: 11274963.
      View in: PubMed
    27. Lee I. K,Yun B. S.,Kim K. T., Choi B. H., Park T. J.,Kim Y. H., Yoo I. D. . Journal of Microbiology and Biotechnology. Citrinin hydrate inhibits serotonin N-acetyltransferase catalyzing the conversion of serotonin to N-acetylserotonin. 2001.
    28. Oh KS, Park TJ, Choi BH, Lee DK, Lee TK, Kim KT. Inhibition of nicotinic receptor-mediated catecholamine secretion by Dryobalanops aromatica in bovine adrenal chromaffin cells. Pharmacol Res. 2000 Dec; 42(6):559-64. PMID: 11058409.
      View in: PubMed
    29. Kim YJ, Hur EM, Park TJ, Kim KT. Nongenomic inhibition of catecholamine secretion by 17beta-estradiol in PC12 cells. J Neurochem. 2000 Jun; 74(6):2490-6. PMID: 10820210.
      View in: PubMed
    30. Chae HD, Park TJ, Lee YK, Lee TG, Kim KT. Rapid and simple measurement of serotonin N-acetyltransferase activity by liquid biphasic diffusion assay. Neurochem Int. 1999 Dec; 35(6):447-51. PMID: 10524712.
      View in: PubMed
    31. Lee IS, Park TJ, Suh BC, Kim YS, Rhee IJ, Kim KT. Chlorpromazine-induced inhibition of catecholamine secretion by a differential blockade of nicotinic receptors and L-type Ca2+ channels in rat pheochromocytoma cells. Biochem Pharmacol. 1999 Sep 15; 58(6):1017-24. PMID: 10509754.
      View in: PubMed
    32. Kim YH, Park TJ, Lee YH, Baek KJ, Suh PG, Ryu SH, Kim KT. Phospholipase C-delta1 is activated by capacitative calcium entry that follows phospholipase C-beta activation upon bradykinin stimulation. J Biol Chem. 1999 Sep 10; 274(37):26127-34. PMID: 10473563.
      View in: PubMed
    33. Park TJ, Lee IS, Ha H, Kim KT. Temperature sensitivity of catecholamine secretion and ion fluxes in bovine adrenal chromaffin cells. Mol Cells. 1999 Feb 28; 9(1):67-71. PMID: 10102574.
      View in: PubMed
    34. Choi SY, Chae HD, Park TJ, Ha H, Kim KT. Characterization of high affinity neurotensin receptor NTR1 in HL-60 cells and its down regulation during granulocytic differentiation. Br J Pharmacol. 1999 Feb; 126(4):1050-6. PMID: 10193787.
      View in: PubMed
    35. Kim KT, Choi SY, Park TJ. Neomycin inhibits catecholamine secretion by blocking nicotinic acetylcholine receptors in bovine adrenal chromaffin cells. J Pharmacol Exp Ther. 1999 Jan; 288(1):73-80. PMID: 9862755.
      View in: PubMed
    36. Park TJ, Chung S, Han MK, Kim UH, Kim KT. Inhibition of voltage-sensitive calcium channels by the A2A adenosine receptor in PC12 cells. J Neurochem. 1998 Sep; 71(3):1251-60. PMID: 9721751.
      View in: PubMed
    37. Park TJ, Shin SY, Suh BC, Suh EK, Lee IS, Kim YS, Kim KT. Differential inhibition of catecholamine secretion by amitriptyline through blockage of nicotinic receptors, sodium channels, and calcium channels in bovine adrenal chromaffin cells. Synapse. 1998 Jul; 29(3):248-56. PMID: 9635895.
      View in: PubMed
    38. Park TJ, Song SK, Kim KT. A2A adenosine receptors inhibit ATP-induced Ca2+ influx in PC12 cells by involving protein kinase A. J Neurochem. 1997 May; 68(5):2177-85. PMID: 9109546.
      View in: PubMed
    39. Suh BC, Park TJ, Kim KT. Synergistic activation of adenylyl cyclase is dependent upon phospholipase C-mediated processes in human neuroblastoma SK-N-BE(2)C cells. Eur J Pharmacol. 1996 Oct 24; 314(1-2):235-42. PMID: 8957241.
      View in: PubMed
    40. Park TJ, Kim KT. Cyclic AMP-independent inhibition of voltage-sensitive calcium channels by forskolin in PC12 cells. J Neurochem. 1996 Jan; 66(1):83-8. PMID: 8522993.
      View in: PubMed
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