Maria G. Castro, Ph.D.

R. C. Schneider Collegiate Professor of Neurosurgery
Professor, Cell and Developmental Biology
734-764-0850

Biography

Maria G. Castro, Ph.D. is a Professor of Neurosurgery and Cell and Developmental Biology at the University of Michigan, School of Medicine.  Her research program aims to develop immunotherapies for primary and metastatic brain cancer, studying basic immune-biology mechanisms leading to clinical implementation. She is investigating the role of the tumor immune-microenvironment in tumor progression and response to therapeutics; crosstalk between cancer cells and hematopoietic stem/progenitor cells, and mechanisms affecting the migration of immune cells from peripheral lymphoid organs to the tumor microenvironment. Her innovative work has led to an FDA approved gene therapy Phase 1 clinical trial for malignant brain cancer which will start at the University of Michigan in the Winter 2013-2014.

Areas of Interest

  • Antigen Processing/Presentation
  • Cell Homing/Trafficking
  • Cytokine Networks
  • Innate Immunity
  • T Cell Activation
  • Viral Infections in the brain
  • Gene Delivery
  • Nanotechnology
  • Hematopoiesis
  • Cell Signaling
  • Immune Suppression
  • Cancer
  • T Cell Biology
  • Animal Models of Disease
  • Vaccine Development
  • Gene Therapy
 

Research Focus

Development of immunotherapies for primary and metastatic brain cancer: from basic immunobiology mechanisms to translational immune-therapeutics. Tumor immune-microenvironment: its role in tumor progression and response to therapeutics. Cross talk between cancer cells and hematopoietic stem/progenitor cells. Mechanisms affecting the migration of immune cells from peripheral lymphoid organs to the tumor microenvironment.

Current Research Activity

  • “Role of brain tumor ligands in the differentiation and maturation of myeloid hematopoietic precursor cells: Impact on anti-tumor immunity”. 
  • “The hematopoietic stem cell niche in brain cancer: Impact tumor progression on anti-tumor immunity”.
  • “Gutless adenovirus vectors encoding immune-stimulatory cytokines and conditional cytotoxic genes to develop anti-glioblastoma multiforme immunotherapies.”
  • “Role of RAGE signalling in glioblastoma multiforme preclinical in vivo models: Impact on innate immunity.”
  • “Role of STAT3 signaling in anti-glioblastoma multiforme immunotherapies: Role on dendritic cells’ vaccination efficacy, antigen presentation, and effector T cells.”
  • “Sleeping beauty tranposase mediated insertion of oncogenes and tumor suppressor genes to create novel brain cancer models: Impact on the tumor microenvironment and anti-tumor immunity.”

Honors & Awards

  • Breakout Session Chair/Moderator:  “Opportunities and Challenges of Nanomedicine in Neuro-Oncology”, BioInterfaces Institute meeting, Ann Arbor, MI, November 1-2, 2013.
  • Member, Program Organizing Committee, American Society of Cell and Gene Therapy, May, 2011 – June, 2013.
  • Biography included in 2010-2011 Edition of Sutton Who’s Who in North America by Sutton Who’s Who in Elite Healthcare as an Honored Member.
  • Chair and Co-Organizer, Symposium: “New Therapeutic Strategies for Neuro-Ophthalmic Diseases” American Society of Cell and Gene Therapy 14th Annual Meeting, Seattle, WA, May 18-21, 2011.
  • Chair, Session 9:  “Brain tumors and the immune system”, 2011 FASEB Summer Research Conference:  “Translational Neuroimmunology: From Mechanisms to Therapeutics”, Carefree, Arizona, July 31-August 5, 2011.
  • Chair, Symposium: “MicroRNA and siRNA Roles in Disease Progression and Development of Novel Therapeutic Targets”, American Society of Cell and Gene Therapy Annual Meeting, May 19-23, 2010.
  • Co-Chair, Symposium: “Oral Session 235 – Immunologic & Host Responses in Gene & Cell Therapy, American Society of Cell and Gene Therapy Annual Meeting, Washington, DC, May 19-23, 2010.
  • Chair, American Society of Gene and Cell Therapy Neural Disorders Gene Therapy Committee, June 2009 – June 2010.
  • Women of Action Award”, Israel Cancer Research Fund (ICRF) for achievements in the field of: Brain Cancer biology and therapeutics”, Beverly Hills, CA August, 2008.
  • Visiting Professor, Wake Forest University School of Medicine, Comprehensive Cancer Center, Brain Tumor Center of Excellence, Winston-Salem, NC, December, 2007.
  • The American Brain Tumor Association (ABTA) Mentoring Award to mentor a medical student in 2007 Medical Student Summer Fellowship Program to conduct basic brain tumor research:  Recipient – Ms. Sharon Lee, Albany Medical College, Albany, NY.
  • The Medallions Group Endowed Chair in Cancer Gene Therapeutics Research, Cedars-Sinai Medical Center, Los Angeles, California, USA, 2006.
  • Best Keynote Speaker Award at 2nd International Symposium on CNS Germ Cell Tumors, “Gene therapy strategies of potential application to recurrent primary CNS Germ Cell Tumors, Universal City, CA USA, November 18-21, 2005.
  • Biography included in “Who’s Who in American Education”, 2004-2005 6th Edition, outstanding achievements; “Who’s Who in Science and Engineering”, 2003-2004 7th Edition, latest achievements in genetics; “Who’s Who in The World”, 2003 20th Edition, most significant record of achievement; “Who’s Who in America”, 2003 57th Edition, country’s most accomplished women in the 21st century;  “Who’s Who in Medicine and Healthcare, 2002-2003 4th Edition, Most Accomplished Healthcare and Medical Professionals Worldwide; “Who’s Who of American Women”,  2002 23rd Edition, Most Accomplished Women from the USA and Canada; Who’s Who” in Medicine and Healthcare, Who’s Who in Science and Engineering and Who’s Who in The World, 2001 Edition for significant record of achievement in the field of Molecular Medicine and Gene Therapy. Published by Marquis, USA. 
  • Biography included in “One Thousand Great Scientists”, published by International Biographical Centre, Cambridge, England.  The bio appeared in the 2002 1st Edition containing a listing of prominent scientists worldwide.
  • Biography included in “Dictionary of International Biography", 29th Edition, International Biographical Center, Cambridge CB2 3QP, 2001.
  • Siebens Foundation Fellowship Award to attend and present work at The Harold W. Siebens Conference:  Cytoreductive Gene Therapy.  The Mayo Foundation, May 25th – 27th September, 1999, Rochester, Minnesota, USA, 1999.
  • Prize for best basic science presentation: Outcomes of brain tumor gene therapy using conditional cytotoxicity: inflammation, white matter lesions, and transgene expression. Lowenstein, P.R., Morrissey, G., Stone, D., Southgate, T., Dewey, R., Mee, A., Bolognani, F. and Castro, M.G. 19th Annual Meeting of the British Neuro-oncology Group, 24th -25th June 1999, Edinburgh, Scotland, UK, 1999.
  • The 'Prof. B Houssay Award' to the best PhD thesis:  'The physiology of ACTH and -MSH secretion in Aves', F. C.Iturriza, M. G. Castro and F. E. Estivariz, 1987.
  • Fogarty International Fellowship Award:  National Institutes of Health, Bethesda, MD, USA 1986-1989 (Post-Doctoral Award).

Credentials

Undergraduate

BSc Hons (1st Class) Chemistry, School of Biological Sciences, National University of La Plata, Argentina, 1979

Master Degrees

M.Sc. - Biochemistry, School of Biological Sciences, National University of La Plata, 1981

M.Sc. - Education Technology, School of Biological Sciences, National University of La Plata, 1986

Post-Graduate Degree

Ph.D. - Biochemistry, School of Biological Sciences, National University of La Plata, 1986

Fellowships

Institute for Endocrine Studies, School of Medicine, National University of Argentina at La Plata, 1983

Institute for Endocrine Studies, School of Medicine, National University of Argentina at La Plata, 1986

Advanced Fellowship

Fogarty International Visiting Research Fellow, Laboratory of Neurochemistry and Neuro-immunology, National Institute of Child Health and Human Development, National Institutes of Health, 1988

Post-Doctoral Fellowship

Laboratory of  Molecular Endocrinology, Department of Biochemistry and Physiology, University of Reading, United Kingdom, 1990

Representative Publications

  1. Candolfi M, Yagiz K, Wibowo M, Ahlzadeh GH, Puntel M, Kamran N, Paran C, Ghiasi H, Lowenstein PR, and Castro MG.  (2013)  Temozolomide does not impair gene therapy-mediated antitumor immunity in syngeneic brain tumor models.  Clinical Cancer Research (accepted for publication pending minor revisions).
  2. MineharuY, Muhammad AG, Yagiz K, Candolfi M, Kroeger KM, Xiong W, Puntel M, Lui C, Levy E, Lugo C, Kocharian A, Allison J, Curran M, Lowenstein PR, and Castro MG.  (2012) Gene therapy-mediated reprogramming tumor infiltrating T cells using IL-2 and inhibiting NF-kB signaling improves the efficacy of immunotherapy in a brain cancer model.  Neurotherapeutics, 2012 October; 9(4):827-43.  PMCID:  PMC3480576.
  3. Sanderson NS, Puntel M, Kroeger KM, Bondale NS, Swerdlow M, Iranmanesh N, Yagita H, Ibrahim A, Castro MG, Lowenstein PR.  (2012) Cytotoxic immunological synapses do not restrict the action of interferon-γ to antigenic target cells.  The Proceedings of the National Academy of Sciences, USA, 2012 May 15: 109(20):  7835-40.  Epub April 30, 2012.  PMCID:  PMC3356634.
  4. Mineharu Y, King G, Muhammad AKM, Bannykh S, Kroeger K, Liu C, Lowenstein PR, Castro MG (2011)  Engineering the brain tumor microenvironment enhances the efficacy of dendritic cells' vaccination: implications for clinical trials design. Clinical Cancer Research, 17(14), 4705-4718. Epub June 1, 2011.  PMCID:  PMC3205808.
  5. King GD, Muhammad AG, Larocque D, Kelson KR, Xiong W, Liu C, Sanderson NS, Kroeger KM, Castro MG, Lowenstein PR. (2011) Combined Flt3L/TK gene therapy induces immunological surveillance which mediates an immune response against a surrogate brain tumor neo-antigen. Molecular Therapy, 2011 Oct; 19(10):1793-801. Epub April 19, 2011.  PMCID:  PMC3188756.
  6. Larocque D, Sanderson NRS, Bergeron J, Curtin J, Girton J, Wibowo M, Bondale N, Kroeger KM, Yang J, Lacayo LM, Reyes KC, Farrokh C, Pechnick RN, Castro MG, Lowenstein PR, (2010) Exogenous fms-like tyrosine kinase 3 ligand overrides brain immune privilege and facilitates recognition of a neo-antigen without causing autoimmune neuropathology. The Proceedings of the National Academy of Sciences, USA, 107(32):14443-14448. Epub July 26, 2010.  PMCID:  PMC2922551.
  7. Candolfi M, Xiong W, Yagiz K, Liu C, Muhammad AK, Puntel M, Foulad D, Zadmehr A, Ahlzadeh GE, Kroeger KM, Tesarfreund M, Lee S, Debinski W, Sareen D, Svendsen CN, Rodriguez R, Lowenstein PR, Castro MG. (2010) Gene therapy-mediated delivery of targeted cytotoxins for glioma therapeutics. The Proceedings of the National Academy of Sciences, USA, 107(46):20021-20026. Epub Oct. 28, 2010.  PMCID:  PMC2993419.
  8. Candolfi M, Yagiz K, Foulad D, Ahlsadeh GE, Tesarfreund M, Muhammad AKM, Puntel M, Kroeger KM, Liu C, Lee S, Curtin J, King GD, Lerner J, Sato K, Mineharu Y, Xiong W, Lowenstein PR, Castro MG. (2009) Release of HMGB1 in response to pro-apoptotic glioma killing strategies: efficacy and neurotoxicity. Clinical Cancer Research 15(13):4401-4414. Portrayed on the highlights section of Cancer Research.  PMCID: PMC2769255.
  9. Curtin JF, Liu N, Candolfi M, Xiong W, Assi H, Yagiz Y, Edwards MR, Michelsen KS, Kroeger KM, Liu C, Muhammad AKM, Clark MC, Arditi M, Comin-Anduix B, Ribas A, Lowenstein PR, Castro MG. (2009) HMGB1 mediates endogenous TLR2 activation and brain tumor regression. PLoS Medicine 6(1); e10.  PMCID:  PMC2621261.
  10. Yang J, Sanderson N, Wawrowsky K, Castro MG, Lowenstein PR. (2010) Kupfer-type immunological synapse characteristics do not predict anti-brain tumor cytolytic T-cell functions in vivo. The Proceedings of the National Academy of Sciences, USA, 107(10):4716-4721. Epub Jan 19, 2010. PMCID:  PMC2842057.

Grants

  • 2013-2015  Inhibiting glioma invasion using targeted nanoparticles; Sponsor: NIH
  • 2013-2018  Mechanisms of glioma growth and invasion - Novel therapeutic strategies; Sponsor: NIH
  • 2013-2015  A non-randomized, open-label dose-finding trial of combined cytotoxic and immune stimulatory strategy for the treatment of resectable primary malignant glioma; Sponsor: Phase ONE
  • 2011-2014  Gutless Adenovirus Mediated Gene Therapy for Glioma; Sponsor: NIH
  • 2011-2014  Gutless Adenovirus Mediated Gene Therapy for Glioma S1: NIH
  • 2011-2014  Brain immune response: Cellular & Molecular Mechanisms; Sponsor: NIH
  • 2011-2016  Crosstalk between glioma cells & immune cells in the tumor microenvironment: Therapeutic implications; Sponsor: NIH
  • 2011-2013  Gene Therapy and the Brain: Neuroimmune Interactions; Sponsor: NIH
  • 2011-2013  Engineering the Brain Immune System for Tumor Therapy; Sponsor: NIH

Published Articles via PubMed

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