Margarita Gutova, Ph.D.

800-826-4673
Margarita Gutova Christine Brown Lab
Research Associate Professor, Department of Stem Cell Biology and Regenerative Medicine
Research Area
Regenerative Therapies for Central Nervous System Diseases
Neural Stem Cell and Immunotherapy Approach
Stem Cell Biology
NSC-mediated Enzyme/prodrug Therapy
Pediatric Brain Tumor Models
Stem Cell Manufacturing, Terumo BCT
Development of Neural Stem Cells for Neurodegenerative Diseases
Research Teams
Developmental and Stem Cell Biology

Margarita Gutova, Ph.D. is a research associate professor working on the development of cellular therapies for brain tumors and injury. Dr. Gutova’s research program explores the signals that control cell proliferation and differentiation in the central nervous system and their dysregulation in brain tumors and injury. Dr. Gutova’s studies are focused on developing combinational approaches to improve cell-mediated therapies to brain tumors and injury. Dr. Gutova's current areas of interest include:

  1. Discovering oncogenic drivers and creating in vitro 3D models for drug screening
  2. Developing new stem cell lines and identifying new approaches for therapeutic cell delivery
  3. Engineering de novo anti-tumor immunity using patient-specific chimeric antigen receptor (CAR)-modified T cells in combination with a small molecule Wnt/β-catenin pathway modulator.
Dr. Gutova is a Sacchi Award Scholar and a recipient of National Cancer Institute and National Institute of Neurological Disorders and Stroke awards for the treatment of brain tumors and traumatic brain injury.

Location

Education & Experience

Fellowship

  • 2004-2008, Postdoctoral Research Fellow, Divisions of Hematology & Hematopoietic Cell Transplantation, and Neurosciences, City of Hope, Duarte, CA

Residency

  • 1994-1998, Residency, Internal Medicine, Pediatric Medical Academy, St. Petersburg

Professional Experience

  • 2014-present, Research Associate Professor, Department of Stem Cell Biology and Regenerative Medicine, City of Hope, Duarte, CA

  • 2010-2014, Assistant Research Professor, Department of Neurosciences, City of Hope, Duarte, CA

  • 2008-2010, Staff Scientist, Department of Neurosciences, Aboody Stem Cell Laboratory, City of Hope, Duarte, CA

  • 2001-2004, Research Fellow and Instructor, Department of Biochemistry, California State University Los Angeles, CA

  • 1998-2001, Physician, Internal Medicine, Pediatric Medical Academy, St. Petersburg

Research

Lab Members

My research is focused on the development of a novel stem cell-mediated therapies for the treatment of brain tumors and injury. Neural stem cells (NSCs) promote cellular regeneration by mechanisms such as delivery of growth factors, suppressing inflammation, reducing axonal injury, and/or by differentiating into mature neural-lineage brain cells. Development of therapies using an allogeneic NSCs, genetically modified to express a human L-Myc gene (LM-NSC008) (Li, Oganesyan et al. 2016, Rockne, Adhikarla et al. 2018) is a focus of my research program. These NSCs, delivered intranasally, intracranially or intrathecally, have demonstrated robust migration towards brain tumors and brain injury sites (lacking tumorigenicity), making them attractive candidates for cell repair/replacement therapies.  
 
I am also interested in a role of Wnt/β-catenin signaling plays in the development and maintenance of multiple organ systems. The Wnt/β-catenin signaling pathway is evolutionary conserved and is a critical regulator of both somatic stem cells and cancer stem cells (CSC). Using the selective small molecule antagonist of the CBP/β-catenin interaction I am investigating a role of CBP/β-catenin in reprogramming of glioma microenvironment and development of de novo combinational strategy to overcome limitations of immunotherapy. I am also interested in the development of an in vitro 3D platform from patient-derived tumors for the high-throughput drug screening and precision medicine applications. 

Awards & Memberships

Awards

  • 2017, The Best Publication of 2016-2017, ISSCR

  • 2015, Keynote Speaker, Phacilitate Cell & Gene Therapy Forum

  • 2013, Keynote Speaker, Stem Cells & Cellular Therapy Business Summit

  • 2011, IND preparation/assistance: First-in-Human Phase I NSC-Mediated Enzyme/Prodrug Therapy for Glioma and Iron Labeling of NSCs, City of Hope

  • 2011, United States Patent No. 20070244046, USPTO
    2011, World Stem Cell Summit second place award, World Stem Cell Summit

  • 2009, Keynote Speaker, 10th Bergen Conference on Cancer Research

  • 2006, AACR Fellowship Award, AACR

  • 2002, National Science Foundation Fellowship Award, CSULA

  • 2002, Society for Neuroscience First place award, CSULA

Memberships

  • 2006, Member, American Association of Cancer Research

  • 2007, Member, Society of Neuro-Oncology

  • 2008, Member, American Society for Gene and Cellular Therapy

  • 2008, Member, Society of Pediatric Neuro-Oncology

  • 2008, Member, International Society of Stem Cell Research

Publications

  • Barish ME, Herrmann K, Tang Y, Argalian Herculian S, Metz M, Aramburo S, Tirughana R, Gutova M, Annala A, Moats RA, Goldstein L, Rockne RC, Gutierrez J, Brown CE, Ghoda L, Aboody KS. Human Neural Stem Cell Biodistribution and Predicted Tumor Coverage by a Diffusible Therapeutic in a Mouse Glioma Model. Stem Cells Transl Med. 2017 Jun;6(6):1522-1532. DOI: 10.1002/sctm.16-0397. Epub 2017 May 8. PMID: 28481046 Free Article Similar articles Select item 28345025
  • Gutova M, Goldstein L, Metz M, Hovsepyan A, Tsurkan LG, Tirughana R, Tsaturyan L, Annala AJ, Synold TW, Wan Z, Seeger R, Anderson C, Moats RA, Potter PM, Aboody KS. Optimization of a Neural Stem-Cell-Mediated Carboxylesterase/Irinotecan Gene Therapy for Metastatic Neuroblastoma. Mol Ther Oncolytics. 2016 Dec 14;4:67-76. DOI: 10.1016/j.omto.2016.11.004. eCollection 2017 Mar 17. PMID: 28345025 Free PMC Article
  • Li Z, Oganesyan D, Mooney R, Rong X, Christensen MJ, Shahmanyan D, Perrigue PM, Benetatos J, Tsaturyan L, Aramburo S, Annala AJ, Lu Y, Najbauer J, Wu X, Barish ME, Brody DL, Aboody KS, Gutova M. L-MYC Expression Maintains Self-Renewal and Prolongs Multipotency of Primary Human Neural Stem Cells. Stem Cell Reports. 2016 Sep 13;7(3):483-95. PubMed PMID: 27546534; PubMed Central PMCID: PMC5031988.
  • Gutova M, Frank JA, D'Apuzzo M, Khankaldyyan V, Gilchrist MM, Annala AJ, Metz MZ, Abramyants Y, Herrmann KA, Ghoda LY, Najbauer J, Brown CE, Blanchard MS, Lesniak MS, Kim SU, Barish ME, Aboody KS, Moats RA. Magnetic resonance imaging tracking of ferumoxytol-labeled human neural stem cells: studies leading to clinical use. Stem Cells Transl Med. 2013 Oct;2(10):766-75. PubMed PMID: 24014682; PubMed Central PMCID: PMC3785261.
  • Aboody KS, Najbauer J, Metz MZ, D'Apuzzo M, Gutova M, Annala AJ, Synold TW, Couture LA, Blanchard S, Moats RA, Garcia E, Aramburo S, Valenzuela VV, Frank RT, Barish ME, Brown CE, Kim SU, Badie B, Portnow J. Neural stem cell-mediated enzyme/prodrug therapy for glioma: preclinical studies. Sci Transl Med. 2013 May 8;5(184):184ra59. PubMed PMID: 23658244; PubMed Central PMCID: PMC3864887.
  • Gutova M, Shackleford GM, Khankaldyyan V, Herrmann KA, Shi XH, Mittelholtz K, Abramyants Y, Blanchard MS, Kim SU, Annala AJ, Najbauer J, Synold TW, D'Apuzzo M, Barish ME, Moats RA, Aboody KS. Neural stem cell-mediated CE/CPT-11 enzyme/prodrug therapy in transgenic mouse model of intracerebellar medulloblastoma. Gene Ther. 2013 Feb;20(2):143-50. PubMed PMID: 22402322; PubMed Central PMCID: PMC4149468.
  • Najbauer J, Huszthy PC, Barish ME, Garcia E, Metz MZ, Myers SM, Gutova M, Frank RT, Miletic H, Kendall SE, Glackin CA, Bjerkvig R, Aboody KS. Cellular host responses to gliomas. PLoS One. 2012;7(4):e35150. PubMed PMID: 22539956; PubMed Central PMCID: PMC3335155.
  • Zhao D, Najbauer J, Garcia E, Metz MZ, Gutova M, Glackin CA, Kim SU, Aboody KS. Neural stem cell tropism to glioma: critical role of tumor hypoxia. Mol Cancer Res. 2008 Dec;6(12):1819-29. PubMed PMID: 19074827.
  • Gutova M, Najbauer J, Frank RT, Kendall SE, Gevorgyan A, Metz MZ, Guevorkian M, Edmiston M, Zhao D, Glackin CA, Kim SU, Aboody KS. Urokinase plasminogen activator and urokinase plasminogen activator receptor mediate human stem cell tropism to malignant solid tumors. Stem Cells. 2008 Jun;26(6):1406-13. PubMed PMID: 18403751.
  • Gutova M, Najbauer J, Gevorgyan A, Metz MZ, Weng Y, Shih CC, Aboody KS. Identification of uPAR-positive chemoresistant cells in small cell lung cancer. PLoS One. 2007 Feb 28;2(2):e243. PubMed PMID: 17327908; PubMed Central PMCID: PMC1800348.
  • Morshed RA, Gutova M, Juliano J, Barish ME, Hawkins-Daarud A, Oganesyan D, Vazgen K, Yang T, Annala A, Ahmed AU, Aboody KS, Swanson KR, Moats RA, Lesniak MS. Analysis of glioblastoma tumor coverage by oncolytic virus-loaded neural stem cells using MRI-based tracking and histological reconstruction. Cancer Gene Ther. 2015 Jan;22(1):55-61. PubMed PMID: 25525033; PubMed Central PMCID: PMC4293243.
  • Metz MZ, Gutova M, Lacey SF, Abramyants Y, Vo T, Gilchrist M, Tirughana R, Ghoda LY, Barish ME, Brown CE, Najbauer J, Potter PM, Portnow J, Synold TW, Aboody KS. Neural stem cell-mediated delivery of irinotecan-activating carboxylesterases to glioma: implications for clinical use. Stem Cells Transl Med. 2013 Dec;2(12):983-92. PubMed PMID: 24167321; PubMed Central PMCID: PMC3841093.
  • Gutova M, Najbauer J, Chen MY, Potter PM, Kim SU, Aboody KS. Therapeutic targeting of melanoma cells using neural stem cells expressing carboxylesterase, a CPT-11 activating enzyme. Curr Stem Cell Res Ther. 2010 Sep;5(3):273-6. PubMed PMID: 19951251.
  • Thu MS, Najbauer J, Kendall SE, Harutyunyan I, Sangalang N, Gutova M, Metz MZ, Garcia E, Frank RT, Kim SU, Moats RA, Aboody KS. Iron labeling and pre-clinical MRI visualization of therapeutic human neural stem cells in a murine glioma model. PLoS One. 2009 Sep 29;4(9):e7218. PubMed PMID: 19787043; PubMed Central PMCID: PMC2746284.
  • Mooney R, Weng Y, Tirughana-Sambandan R, Valenzuela V, Aramburo S, Garcia E, Li Z, Gutova M, Annala AJ, Berlin JM, Aboody KS. Neural stem cells improve intracranial nanoparticle retention and tumor-selective distribution. Future Oncol. 2014 Feb;10(3):401-15. PubMed PMID: 24559447.

 

Information listed here is obtained from PubMed, a public database; City of Hope is not responsible for its accuracy.