Research My research program relates to brain cancer biology, development of immune-therapeutics for primary and metastatic brain cancer; manipulating the brain tumor microenvironment using gene therapy strategies, small molecules and blocking antibodies. Neuro-immunology, ie, in vivo migration of immune cells into the central nervous system and the brain tumor microenvironment. The role of pattern recognition receptors' signaling in cancer immune suppression and brain inflammation. Mechanisms mediated by myeloid derived suppressor cells (MDSCs) in brain cancer biology and response to therapeutics My lab has recently focused its research efforts on DNA repair pathways, the epigenetic regulation of cancer progression, uncovering the role of oncometabolites in the brain tumor microenvironment and in mediating the response to immunotherapies. To this end, we are developing novel rodent models of malignant brain cancer using in vivo gene transfer technologies. To accomplish this, we are using the Sleeping Beauty Transposase System to insert specific genetic lesions in the genome of stem cells lining the third ventricle. These genetically engineered murine models harboring genetic lesions present in the human disease have proven to be powerful platforms to uncover the molecular mechanisms that mediate tumor progression and implement novel immune-mediated gene and/or cell based therapeutic approaches. The ultimate aim of the lab is to develop novel therapeutic approaches to be translated to human Phase I clinical trials. Dr. Castro's innovative work has led to and FDA approved gene therapy Phase I clinical trial for malignant brain cancer which is ongoing at the University of Michigan, Department of Neurosurgery. I have a broad background in cancer biology, mouse models of brain cancer, neuro-immunology, cancer immunology and experimental therapeutics, with specific training and expertise in key research areas for this application. As PI or Co-Investigator on several previous NIH-funded grants, I have laid the groundwork for the implementation of research programs in bran cancer biology and therapeutics, including the development of the relevant animal models, immunological techniques, imaging and molecular approaches. In addition, I successfully administered the projects (e.g.staffing, research protections, budget), collaborated with other researchers, and produced high impact peer-reviewed publications from each project. As a result of these previous experiences, I am aware of the importance of frequent communication among project members and of constructing a realistic research plan, timeline and budget. In summary, I have a demonstrated record of successful and productive research output and project management in an area of high relevance for brain cancer biology and the development of novel therapeutic strategies for primary and metastatic brain tumors.
In The News Dr. Maria Castro Receives Prestigious Javits Neuroscience Investigator Award see the link below for full details.Areas of Interest Antigen Processing/Presentation; Cell Homing/Trafficking; epigenetics; RNA Seq; Bru Seq Technologies; Genetically Engineered Mouse Glioma Models using Sleeping Beauty Transposase Method; DNA Repair Pathways; Oligodendrocyte Development Pathways; 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
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 transposase mediated insertion of oncogenes and
tumor suppressor genes to create novel brain cancer models: Impact on the tumor microenvironment and anti-tumor immunity.
- DNA repair pathways in glioma models, testing of new chemotherapeutic agents.
- Epigenetic modulation in brain cancer.
- Development of novel immunotherapies for both adult and pediatric brain cancers.
Honors & Awards - Javits Neuroscience Investigator Award: for R01 “Immune-suppressive Myeloid Cells in the Glioma
Microenvironment: Signaling Mechanisms and Novel Therapeutic Strategies”, Ann Arbor, MI, February, 2016.
- 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 21stcentury; “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 23rdEdition, 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 forsignificant
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
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