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Home Profiles Agnes Chen, MD

Investigator, Pediatrics
Professor of Pediatrics, David Geffen School of Medicine at UCLA
Chief, Division of Pediatric Neurology, Harbor-UCLA Medical Center

Agnes Chen, MD

Research Areas

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Research

Biography

Dr. Agnes Chen received her medical degree from the Boston University School of Medicine. She completed residency in Pediatrics as well as Adult and Child Neurology at Harbor-UCLA Medical Center. During her training, she began participating in research at The Lundquist Institute in intrathecal enzyme replacement for mucopolysaccharidosis type I. She joined the faculty at Harbor-UCLA right after residency and continues as an investigator at The Lundquist Institute, where she is a member of both the Translational Genomics and Neurotherapeutics Institutes.

Publications

The following is a selected number of articles in disease areas actively studied by members of the Rare Disease section of the Institute for Genomics and Population Sciences.

Lysosomal Storage Diseases (Includes mucopolysaccharidosis types I, II, III, and VI, and Niemann Pick Type C)
  1. L.E. Polgreen, W. Thomas, P.J. Orchard, C.B. Whitley, B.S. Miller.  Effect of Recombinant Human Growth Hormone on Changes in Height, Bone Mineral Density, and Body Composition Over 1-2 Years in Children with Hurler or Hunter Syndrome. Mol Genet Metab. 2014 Feb;111(2):101-6.
  2. Maarup TJ, Chen AH, Porter FD, Farhat NY, Ory DS, Sidhu R, Jiang X, Dickson PI.  Intrathecal 2-Hydroxypropyl-Beta-Cyclodextrin in a Single Patient with Niemann-Pick C1. Mol Genet Metab. 2015, Jul 15. pii: S1096-7192(15)30031-7. https://doi: 10.1016/j.ymgme.2015.07.001.
  3. Le SQ, Kan SH, Clarke D, Sanghez V, Egeland M, Vondrak KN, Doherty TM, Vera MU, Iacovino M, Cooper JD, Sands MS, Dickson PI. “A humoral immune response alters the distribution of enzyme replacement therapy in murine mucopolysaccharidosis type I”. Mol Ther Methods Clin Dev. 2017 16;8:42-51. https://doi: 10.1016/j.omtm.2017.09.008. 
  4. Polgreen LE, Kunin-Batson A, Rudser K, Vehe RK, Utz JJ, Whitley CB, Dickson P. Pilot study of the safety and effect of adalimumab on pain, physical function, and musculoskeletal disease in mucopolysaccharidosis types I and II. Mol Genet Metab Rep. 2017 Jan 15;10:75-80 (PMCID5238608).
  5. Clarke D, Pearse Y, Kan SH, Cooper J, Dickson P, Iacovino M. “Genetically corrected iPSC-derived Neural Stem Cell Grafts deliver enzyme replacement to impact CNS disease in Sanfilippo B Mice”. Mol Ther Methods Clin Dev. 2018 Sep 21;10:113-127. doi: 10.1016/j.omtm.2018.06.005.
  6. Polgreen LE, Lund TC, Braunlin E, Tolar J, Miller BS, Fung EB, Whitley CB, Eisengart JB, Northrop E, Rudser K, Miller WP, Orchard PJ.  Clinical trial of laronidase in Hurler syndrome after hematopoietic cell transplantation. Pediatr Res. 2019 Aug 21. doi: 10.1038/s41390-019-0541-2. [Epub ahead of print]. (PMCID6960090)
  7. Vera M, Le S, Victoroff A, Passage M, Brown J, Crawford B, Polgreen L, Chen A, Dickson P. Evaluation of Non-Reducing End Pathologic Glycosaminoglycan Detection Method for Monitoring Therapeutic Response to Enzyme Replacement Therapy in Human Mucopolysaccharidosis I. Molecular Genetics and Metabolism, September 2019; https://doi.org/10.1016/j.ymgme.2019.09.001. PMID: 31630958
  8. Chen A, Harmatz P, Nestrasil I, Eisengart J, King K, Rudser K, Kaizer A, Svatkova A, Wakumoto A, Le S, Madden J, Young S, Zhang H, Polgreen L, Dickson P. Intrathecal enzyme replacement for cognitive decline in mucopolysaccharidosis type I, a randomized, open-label, controlled pilot study. Molecular Genetics and Metabolism, November 2019; https://doi.org/10.1016/j.ymgme.2019.11.007. PMID: 31839529
  9. Pearse Y, Clarke D, Kan SH, Le SQ, Sanghez V, Luzzi A, Pham I, Nih LR, Cooper JD, Dickson PI, Iacovino M. “Brain transplantation of genetically corrected Sanfilippo type B neural stem cells induces partial cross-correction of the disease.” Mol Ther Methods Clin Dev. 2022 Oct 27;27:452-463. doi: 10.1016/j.omtm.2022.10.013. eCollection 2022 Dec 8
  10. Anakinra in Sanfilippo syndrome: a phase 1/2 trial. Polgreen LE, Chen AH, Pak Y, Luzzi A, Morales Garval A, Acevedo J, Bitan G, Iacovino M, O’Neill C, Eisengart JB. Nat Med. 2024 Sep;30(9):2473-2479. doi: 10.1038/s41591-024-03079-3. Epub 2024 Jun 21. PMCID: PMC11405265
Bone (Includes achondroplasia, autosomal dominant osteopetrosis, autosomal recessive osteopetrosis, osteoporosis)
  1. Wu C, Econs MJ, DiMeglio LA, Insogna KL, Levine MA, Orchard PJ, Miller WP, Petryk A, Rush ET, Shoback DM, Ward LM, Polgreen LE. Diagnosis and Management of Osteopetrosis: Consensus Guidelines from the Osteopetrosis Working Group. J Clin Endocrinol Metab. 2017 Sep 1;102(9):3111-3123.
  2. Savarirayan  R, Tofts  L, Irving  M, Wilcox  W, Bacino  CA, Hoover-Fong  J, Ullot Font  R, Harmatz  P, Rutsch  F, Bober  MB, Polgreen  LE, Ginebreda  I, Mohnike  K, Charrow  J, Hoernschmeyer  D, Ozono  K, Alanay  Y, Arundel  P, Kagami  S, Yasui  N, White  KK, Saal  HM, Leiva-Gea  A, Luna-González  F, Mochizuki H , Basel  D, Porco  DM, Jayaram  K, Fisheleva  E, Huntsman-Labed  A, Day J. Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial. Lancet 2020 Sep 5;396(10252):684-692. doi: 10.1016/S0140-6736(20)31541-5.
  3. Nguyen A, Miller WP, Gupta A, Lund TC, Schiferl D, Lam, LSK Arzumanyan Z, Orchard PJ, Polgreen LE. Open-Label Pilot Study of Interferon Gamma–1b in Patients With Non-Infantile Osteopetrosis. JBMR Plus. 2022 Jan 25;6(3):e10597 https://doi.org/10.1002/jbm4.10597
  4. Polgreen LE, Imel EA, Econs MJ. Autosomal Dominant Osteopetrosis. Bone. 2023 Feb 28;170:116723
  5. Savarirayan R, Wilcox WR, Harmatz P, Phillips J 3rd, Polgreen LE, Tofts L, Ozono K, Arundel P, Irving M, Bacino CA, Basel D, Bober MB, Charrow J, Mochizuki H, Kotani Y, Saal HM, Army C, Jeha G, Qi Y, Han L, Fisheleva E, Huntsman-Labed A, Day J. Vosoritide therapy in children with achondroplasia aged 3-59 months: a multinational, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Child Adolesc Health. 2024 Jan;8(1):40-50. doi: 10.1016/S2352-4642(23)00265-1. Epub 2023 Nov 18.
Other Genetic Disorders (Includes ataxia telangiectasia, muscular dystrophy, adrenal leukodystrophy, myopathy-associated p97/VCP R155H mutations)
  1. Filareto A, Parker S, Darabi R, Borges L, Iacovino M, Schaaf T, Mayerhofer T, Chamberlain JS, Ervasti JM, McIvor RS, Kyba M, Perlingeiro RC. “An ex vivo gene therapy approach to treat muscular dystrophy using inducible pluripotent stem cells.” Nat Commun. 2013;4:1549. doi: 10.1038/ncomms2550.
  2. Petryk A, Polgreen LE, Grames M, Lowe DA, Hodges JS, Karachunski P. Feasibility and tolerability of low-intensity whole body vibration and its effects on muscle function and bone in patients with dystrophinopathies: A pilot study.  Muscle Nerve. 2017 Jun;55(6):875-883 (PMCID:5385164)
  3. Perez H, Abdallah MF, Chavira JI, Norris AS, Egeland MT, Vo KL, Buechsenschuetz CL, Sanghez V, Kim JL, Pind M, Nakamura K, Hicks GG, Gatti RA, Madrenas J, Iacovino M, McKinnon PJ, Mathews PJ. “A novel, ataxic mouse model of ataxia telangiectasia caused by a clinically relevant nonsense mutation”. Elife. 2021 Nov 1;10:e64695. doi: 10.7554/eLife.64695
  4. Luzzi A., Wang F., Li S., Chou TF. Iacovino M*, “Skeletal muscle cell protein dysregulation highlights the pathogenesis mechanism of myopathy-associated p97/VCP R155H mutations” Front Neurol. 2023 Aug 3:14:1211635. doi: 10.3389/fneur.2023.1211635. PMCID: PMC10435852
  5. Zhang, X., Gui, L, Zhang, X, Bulfer, S.L., Sanghez, V. Wong, D., Lee, Y., Lehmann, L., Lee, S.L. Shih, P.Y., Lin, H.J., Iacovino, M., Weihl, C.C., Arkin, M.R., Wang, Y., Chou, T.-F*. “Altered cofactor regulation with disease-associatedp97/VCP mutations. Proc Natl Acad Sci USA 2015 Apr 7;112(14):E1705-14. doi: 10.1073/pnas.1418820112
Hematopoietic disorders (includes sickle cell disease, thrombocytopenia, basic hematopoiesis)
  1. Iacovino M, Chong D, Szatmari I, Hartweck L, Rux D, Caprioli A, Cleaver O and Kyba M. “HoxA3 is an apical regulator of haemogenic endothelium.” Nat Cell Biol. 2011 Jan;13(1):72-8. doi: 10.1038/ncb2137.
  2. 12. Caprioli A*, Koyano-Nakagawa N*, Iacovino M*, Shi X, Ferdous A, Harvey RP, Olson EN, Kyba M, Garry DJ. “Nkx2-5 represses Gata1 gene expression and modulates the cellular fate of cardiac progenitors during embryogenesis.” Circulation. 2011 Apr 19;123(15):1633-41. doi: 10.1161/CIRCULATIONAHA.110.008185. *Co-first author.
  3. Borges L, Iacovino M, Mayerhofer T, Koyano-Nakagawa N, Baik J, Garry DJ, Kyba M, Letarte M, Perlingeiro RC. “A critical role for endoglin in the emergence of blood during embryonic development”. Blood. 2012 Jun 7;119(23):5417-28. doi: 10.1182/blood-2011-11-391896.
  4. Webber BR, Iacovino M, Choi SH, Tolar J, Kyba M, Blazar BR. “DNA methylation of Runx1 regulatory regions correlates with transition from primitive to definitive hematopoietic potential in vitro and in vivo”. Blood 2013 Oct 24;122(17):2978-86. doi: 10.1182/blood-2013-03-489369.
  5. Stavropoulou V., Kaspar S., Brault L., Sanders M.A., Juge S., Morettini S., Tzankov A., Iacovino M., I Lau IJ, Milne T.A., Royo H., Kyba M., Valk P.J., Peters A.H. & Schwaller J. “MLL-AF9 expression in hematopoietic stem cells drives a highly invasive AML expressing EMT-related genes linked to poor outcome.” Cancer Cell 2016 Jul 11;30(1):43-58. doi: 10.1016/j.ccell.2016.05.011.
  6. Sanghez V., Luzzi A., Clarke D., Kee DP., Beuder S., Rux D., Osawa M., Chou TF, Kyba M. and Iacovino M “HoxA3 Induces Ligand cis-Inhibition of the Notch Pathway to Arrest Endothelial to Hematopoietic Transition (EHT)”. Plos One 2017; 12(10):e0186818. doi: 10.1371/journal.pone.0186818.
  7. Gotesman M, Elgar G, Santiago LH, Alvarez A, Pak Y, Lin HJ, Lasky JL, Panosyan EH. Pediatric Patients with Sickle Cell Disease at a Public Hospital: Nutrition, Compliance and Early Experience With L-Glutamine Therapy. In Vivo. 2022 Jul-Aug;36(4):1761-1768. PMID: 35738636.
  8. Panosyan DE, Panosyan WS, Corral I, Hanudel MR, Pak Y, Gotesman M. Sickle Cell Disease Related Vasculopathies and Early Evaluation in a Pediatric Population. In Vivo. 2024 May-Jun;38(3):1203-1212. doi: 10.21873/invivo.13556.
  9. Gotesman M, Shear M, Raheel S, Procassini M, Panosyan EH. Pediatric Immune Thrombocytopenia. Adv Pediatr. 2024 Aug;71(1):229-240. doi: 10.1016/j.yapd.2024.02.007. Epub 2024 Apr 6.
Oncology 
  1. Qing X, Panosyan E, Ji P, Gotesman M, French S, Cai J. Therapy-related myeloid neoplasm in an 18-year-old boy with b-lymphoblastic leukemia. Exp. Mol. Pathol. 2017 Nov 21. PMID: 29155023
  2. Liu J, Guo B, Chen Z, Wang N, Iacovino M, Cheng J, Roden C, Pan W, Khan S, Chen S, Kyba M, Fan R, Guo S, Lu J. “miR-125b promotes MLL-AF9-driven murine acute myeloid leukemia involving a VEGFA-mediated non-cell-intrinsic mechanism”. Blood 2017 Mar 16;129(11):1491-1502. doi: 10.1182/blood-2016-06-721027.
  3. Gotesman M, Vo TT, Herzog L, Tea T, Mallya S, Tasian SK, Konopleva M, Fruman DA. mTOR inhibition enhances efficacy of dasatinib in ABL-rearranged Ph-like B-ALL. Oncotarget. 2018;9: 6562-6571. PMID: 29464092
  4. Stavropoulou V, Almosailleakh M, Royo H, Spetz JF, Juge S, Brault L, Kopp P, Iacovino M, Kyba M, Tzankov A, Stadler MB, Cazzaniga G, Peters AHFM, Schwaller J. “A Novel Inducible Mouse Model of MLL-ENL-driven Mixed-lineage Acute Leukemia”. Hemasphere. 2018 Jun 12;2(4):e51. doi: 10.1097/HS9.0000000000000051.
  5. Gotesman M, Getachew R, Morales S, Zangwill K, Gershman G, Lee S, Lasky JL, Panosyan EH. A Case of Langerhans Cell Histiocytosis with multifocal, single system, GI tract involvement and literature review. Journal of Pediatric Hematology and Oncology, 2019 Nov 22. PMID: 31764515
  6. Johnston E, Martinez I, Davis E, Caudill C, Richman J, Brackett J, Dickens D, Kahn A, Schwalm C, Sharma A, Patel P on behalf of the POCC Consortium, Bhatia S, Levine J, Wolfson J, (Gotesman M, Member of POCC Consortium). SARS-CoV-2 in Childhood Cancer in 2020: A Disease of Disparities. J Clin Oncol. 2021 Dec. PMID 34694886
  7. Bradford K, Nobori A, Johnson B, Allen-Rhoades W, Naik-Mathuria B, Panosyan EH, Gotesman M, Lasky J, Cheng J, Ikeda A, Goldstein J, Singh A, Federman N. Primary Renal Ewing Sarcoma in Children and Adults (Case series). J Pediatr Hematol Oncol. 2020 Apr 10. PMID: 32282650
  8. Morales S, Gotesman M, Su E, Yee J, Ruiz M, Friedlander S, Lasky III J and Panosyan E. Increasing BMI Z-Scores 3 Years after Diagnosis among a Multiethnic Cohort of Childhood Cancer Survivors Treated in South Los Angeles. Journal of Biosciences and Medicines, 10, 141-151. 2022
  9. Martin SD, Davis ES, Dai C, Boal LH, Araya B, Brackett J, Dickens D, Kahn A, Martinez I, Sharma A, Schwalm C, Aguayo-Hiraldo P, Bhatia S, Levine JM, Johnston EE, Wolfson JA; Pediatric Oncology COVID-19 Case Consortium (including Gotesman M). Clinical Features and Risk Factors Associated With Multisystem Inflammatory Syndrome in Children With Cancer and COVID-19. JAMA Oncol. 2023 Aug 1;9(8):1108-1112. doi: 10.1001/jamaoncol.2023.0525. PMCID: PMC10176181
  10. Gotesman M, Raheel S, Panosyan EH. Chronic Myeloid Leukemia in Children and Adolescents. Adv Pediatr. 2023 Aug;70(1):145-155. doi: 10.1016/j.yapd.2023.04.002. Epub 2023 May 12.
Developmental Biology
  1. Iacovino M, Hernandez C, Xu Z, Bajwa G, Prather M, Kyba M. “A conserved role for Hox paralog group 4 in regulation of hematopoietic progenitors.” Stem Cells Dev. 2009 Jun;18(5):783-92. doi: 10.1089/scd.2008.0227.
  2. Szatmari I, Iacovino M, Kyba M. “The retinoid signaling pathway inhibits hematopoiesis and is uncoupled from the Hox complexes during hematopoietic development.” Stem Cells. 2010 Sep;28(9):1518-29. doi: 10.1002/stem.484.
  3. Mallanna SK, Ormsbee BD, Iacovino M, Gilmore JM, Cox JL, Kyba M, Washburn MP, Rizzino A. “Proteomic Analysis of Sox2-associated Proteins During Early Stages of Mouse Embryonic Stem Cell Differentiation Identifies Sox21 as a Novel Regulator of Stem Cell Fate.” Stem Cells. 2010 Oct;28(10):1715-27. doi: 10.1002/stem.494.
  4. Zhu R, Iacovino M, Mahen E, Kyba M, Matin A. “Transcripts that associate with the RNA binding protein, DEAD-END (DND1), in embryonic stem (ES) cells.” BMC Mol Biol. 2011 Aug 18;12:37. doi: 10.1186/1471-2199-12-37.
  5. Mazzoni EO, Mahony S, Iacovino M, Morrison CA, Mountoufaris G, Closser M, Whyte WA, Young RA, Kyba M, Gifford DK, Wichterle H. “Embryonic stem cell-based mapping of developmental transcriptional programs”. Nat Methods 2011 Nov 13;8(12):1056-8. doi: 10.1038/nmeth.1775.
  6. Jain AK, Allton K, Iacovino M, Mahen E, Milczarek RJ, Zwaka TP, Kyba M, Barton MC. “p53 regulates cell cycle and microRNAs to promote differentiation of human embryonic stem cells”. PLoS Biol. 2012;10(2):e1001268. doi: 10.1371/journal.pbio.1001268.
  7. Van den Ameele J, Tiberi L, Bondue A, Paulissen C, Herpoel A, Iacovino M, Kyba M, Blanpain C, Vanderhaeghen P. “Eomesodermin induces Mesp1 expression and cardiac differentiation from embryonic stem cells in the absence of Activin”. (2012) EMBO Rep. 2012 Apr;13(4):355-62. doi: 10.1038/embor.2012.23.
  8. Antonica F, Kasprzyk DF, Opitz R, Iacovino M, Liao XH, Dumitrescu AM, Refetoff S, Peremans K, Manto M, Kyba M, Costagliola S. “Generation of functional thyroid from embryonic stem cells.” Nature. 2012 Nov 1;491(7422):66-71. doi: 10.1038/nature11525.  
  9. Chan SS, Shi X, Toyama A, Arpke RW, Dandapat A, Iacovino M, Kang JJ, Le G, Hagen HR, Garry DJ, Kyba M. “Mesp1 patterns mesoderm into cardiac, hematopoietic, or skeletal myogenic progenitors in a context-dependent manner.” Cell Stem Cell 2013 May 2;12(5):587-601. doi: 10.1016/j.stem.2013.03.004.
  10. Kuang YL, Munoz A, Nalula G, Santostefano KE, Sanghez V, Sanchez G, Terada N, Mattis AN, Iacovino M, Iribarren C, Krauss RM, Medina MW “Evaluation of commonly used ectoderm markers in iPSC trilineage differentiation”. Stem Cell Res. 2019 May;37:101434. doi: 10.1016/j.scr.2019.101434.