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Maria Castro, Ph.D.

Email Address:
maria.castro@cshs.org
Work Email Address:
castromg@cshs.org

Work Address:
8700 Beverly Blvd.
Davis 5090
Los Angeles, CA 90048
UNITED STATES

Fax Number:
310-423-7308
Work Phone Number:
(310) 423-7303



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Department / Division Affiliations
Professor, Department of Medicine
Member, Access Immunity, Microbes, and Molecular Pathogenesis Home Area, Access Molecular Pharmacology: Therapeutics, Diagnostics, and Biology of Disease Home Area, Access Neuroscience Home Area, CTSI, Pharmacology Home Area

Research Interest:

Cellular and molecular mechanisms underlying brain tumor regression and immunological long term memory

Dr. Maria G Castro's group is investigating the cellular and molecular mechanisms underlying brain tumor regression and immunological long term memory in pre-clinical models of glioblastoma (GBM). Her group has uncovered the role of plasmocitoid dendritic cells (pDC) in mediating tumor regression and initiating both the innate and adaptive arms of the immune response against intracranial tumors. Dr. Castro's lab is currently working with knock out mice to establish the phenotype of immune cells responsible for long term memory in the syngeneic GBM models. Dr. Castro's group is establishing gutless and lentivirus vectors with the aim of imaging in vivo and non-invasively the trafficking of activated immune cells in and out of the central nervous system.

Bio:

Dr. Castro is Co-Director of the Board of Governors Gene Therapeutics Research Institute at Cedars-Sinai. Dr. Castro is also Professor of Medicine and Professor of Molecular and Medical Pharmacology at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA). Dr Castro has recently been awarded the Medallion's Group Endowed Chair in Gene Therapeutics at Cedars Sinai Medical Center. She currently serves as a permanent member and consultant at a study section of the National Institute of Neurological Disorders and Stroke, National Institutes of Health. Dr Castro previously served as Professor of Molecular Medicine at the University of Manchester in England. She was a member of the Neuroscience Panel (Study Section) of the Welcome Trust, UK and is an expert member on the Neuroscience Panel for Evaluators of the European Commission. Dr. Castro is the recipient of RO-1 and R0-3 grants from the National Institutes of Health to develop novel gene therapy approaches to treat chronic neurodegenerative brain diseases, such as Parkinson's disease and brain cancer. Dr Castro's research program focuses on the molecular and cellular mechanisms which mediate brain tumor regression in response to immune-stimulatory and cytotoxic gene therapeutics. Dr Castro has published over 200 research articles, reviews and book chapters in high impact peer-reviewed journals, e.g. Nature Medicine, Nature Biotechnology, Proceedings of the National Academy of Medicine USA, The Journal of Experimental Medicine, The Journal of Virology, The Journal of Neuroscience, and Cancer Research amongst many others. Dr Castro serves on the editorial boards of Gene Therapy, Current Gene Therapy, Journal of Endocrinology, Journal of Molecular Endocrinology and Journal of Neuromolecular Medicine.

Publications:

Ferraz-Filho José Roberto L, Torres Ulysses S, Teixeira Augusto César V, Castro Maria Laura S, Dias Marco Antonio F Ectopic growth hormone-secreting pituitary adenoma involving the clivus treated with octreotide: role of magnetic resonance imaging in the diagnosis and clinical follow-up. Arquivos de neuro-psiquiatria. 2012; 70(9): 744-5.
Mineharu Yohei, Muhammad A K M Ghulam, Yagiz Kader, Candolfi Marianela, Kroeger Kurt M, Xiong Weidong, Puntel Mariana, Liu Chunyan, Levy Eva, Lugo Claudia, Kocharian Adrina, Allison James P, Curran Michael A, Lowenstein Pedro R, Castro Maria G Gene therapy-mediated reprogramming tumor infiltrating T cells using IL-2 and inhibiting NF-κB signaling improves the efficacy of immunotherapy in a brain cancer model. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 2012; 9(4): 827-43.
Zirger Jeffrey M, Puntel Mariana, Bergeron Josee, Wibowo Mia, Moridzadeh Rameen, Bondale Niyati, Barcia Carlos, Kroeger Kurt M, Liu Chunyan, Castro Maria G, Lowenstein Pedro R Immune-mediated loss of transgene expression from virally transduced brain cells is irreversible, mediated by IFNγ, perforin, and TNFα, and due to the elimination of transduced cells. Molecular therapy : the journal of the American Society of Gene Therapy. 2012; 20(4): 808-19.
Candolfi Marianela, King Gwendalyn D, Yagiz Kader, Curtin James F, Mineharu Yohei, Muhammad A K M Ghulam, Foulad David, Kroeger Kurt M, Barnett Nick, Josien Regis, Lowenstein Pedro R, Castro Maria G Plasmacytoid dendritic cells in the tumor microenvironment: immune targets for glioma therapeutics. Neoplasia (New York, N.Y.). 2012; 14(8): 757-70.
Lowenstein Pedro R, Castro Maria G Pushing the limits of glioma resection using electrophysiologic brain mapping. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012; 30(20): 2437-40.
Muhammad A K M Ghulam, Xiong Weidong, Puntel Mariana, Farrokhi Catherine, Kroeger Kurt M, Salem Alireza, Lacayo Liliana, Pechnick Robert N, Kelson Kyle R, Palmer Donna, Ng Philip, Liu Chunyan, Lowenstein Pedro R, Castro Maria G Safety profile of gutless adenovirus vectors delivered into the normal brain parenchyma: implications for a glioma phase 1 clinical trial. Human gene therapy methods. 2012; 23(4): 271-84.
Candolfi Marianela, Curtin James F, Yagiz Kader, Assi Hikmat, Wibowo Mia K, Alzadeh Gabrielle E, Foulad David, Muhammad A K M G, Salehi Sofia, Keech Naomi, Puntel Mariana, Liu Chunyan, Sanderson Nicholas R, Kroeger Kurt M, Dunn Robert, Martins Gislaine, Lowenstein Pedro R, Castro Maria G B cells are critical to T-cell-mediated antitumor immunity induced by a combined immune-stimulatory/conditionally cytotoxic therapy for glioblastoma. Neoplasia (New York, N.Y.). 2011; 13(10): 947-60.
King Gwendalyn D, Muhammad A K M Ghulam, Larocque Daniel, Kelson Kyle R, Xiong Weidong, Liu Chunyan, Sanderson Nicholas S R, Kroeger Kurt M, Castro Maria G, Lowenstein Pedro R Combined Flt3L/TK gene therapy induces immunological surveillance which mediates an immune response against a surrogate brain tumor neoantigen. Molecular therapy : the journal of the American Society of Gene Therapy. 2011; 19(10): 1793-801.
Mineharu Yohei, King Gwendalyn D, Muhammad A K M G, Bannykh Serguei, Kroeger Kurt M, Liu Chunyan, Lowenstein Pedro R, Castro Maria G Engineering the brain tumor microenvironment enhances the efficacy of dendritic cell vaccination: implications for clinical trial design. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011; 17(14): 4705-18.
Castro Maria G, Candolfi Marianela, Kroeger Kurt, King Gwendalyn D, Curtin James F, Yagiz Kader, Mineharu Yohei, Assi Hikmat, Wibowo Mia, Ghulam Muhammad A K M, Foulad David, Puntel Mariana, Lowenstein Pedro R Gene therapy and targeted toxins for glioma. Current gene therapy. 2011; 11(3): 155-80.
Puntel Mariana, Barrett Robert, Sanderson Nicholas S R, Kroeger Kurt M, Bondale Niyati, Wibowo Mia, Kennedy Sean, Liu Chunyan, Castro Maria G, Lowenstein Pedro R Identification and visualization of CD8+ T cell mediated IFN-γ signaling in target cells during an antiviral immune response in the brain. PloS one. 2011; 6(8): e23523.
Puntel Mariana, Muhammad A K M G, Candolfi Marianela, Salem Alireza, Yagiz Kader, Farrokhi Catherine, Kroeger Kurt M, Xiong Weidong, Curtin James F, Liu Chunyan, Bondale Niyati S, Lerner Jonathan, Pechnick Robert N, Palmer Donna, Ng Philip, Lowenstein Pedro R, Castro Maria G A novel bicistronic high-capacity gutless adenovirus vector that drives constitutive expression of herpes simplex virus type 1 thymidine kinase and tet-inducible expression of Flt3L for glioma therapeutics. Journal of virology. 2010; 84(12): 6007-17.
Saghizadeh Mehrnoosh, Kramerov Andrei A, Yaghoobzadeh Yousha, Hu Jinwei, Ljubimova Julia Y, Black Keith L, Castro Maria G, Ljubimov Alexander V Adenovirus-driven overexpression of proteinases in organ-cultured normal human corneas leads to diabetic-like changes. Brain research bulletin. 2010; 81(2-3): 262-72.
Larocque Daniel, Sanderson Nicholas S R, Bergeron Jose, Curtin James F, Girton Joe, Wibowo Mia, Bondale Niyati, Kroeger Kurt M, Yang Jieping, Lacayo Liliana M, Reyes Kevin C, Farrokhi Catherine, Pechnick Robert N, Castro Maria G, Lowenstein Pedro R Exogenous fms-like tyrosine kinase 3 ligand overrides brain immune privilege and facilitates recognition of a neo-antigen without causing autoimmune neuropathology. Proceedings of the National Academy of Sciences of the United States of America. 2010; 107(32): 14443-8.
Kroeger Kurt M, Muhammad A K M Ghulam, Baker Gregory J, Assi Hikmat, Wibowo Mia K, Xiong Weidong, Yagiz Kader, Candolfi Marianela, Lowenstein Pedro R, Castro Maria G Gene therapy and virotherapy: novel therapeutic approaches for brain tumors. Discovery medicine. 2010; 10(53): 293-304.
Candolfi Marianela, Xiong Weidong, Yagiz Kader, Liu Chunyan, Muhammad A K M G, Puntel Mariana, Foulad David, Zadmehr Ali, Ahlzadeh Gabrielle E, Kroeger Kurt M, Tesarfreund Matthew, Lee Sharon, Debinski Waldemar, Sareen Dhruv, Svendsen Clive N, Rodriguez Ron, Lowenstein Pedro R, Castro Maria G Gene therapy-mediated delivery of targeted cytotoxins for glioma therapeutics. Proceedings of the National Academy of Sciences of the United States of America. 2010; 107(46): 20021-6.
Puntel Mariana, Kroeger Kurt M, Sanderson Nicholas S R, Thomas Clare E, Castro Maria G, Lowenstein Pedro R Gene transfer into rat brain using adenoviral vectors. Current protocols in neuroscience / editorial board, Jacqueline N. Crawley ... [et al.]. 2010; Chapter 4(2-3): Unit 4.24.
Xiong Weidong, Candolfi Marianela, Liu Chunyan, Muhammad A K M Ghulam, Yagiz Kader, Puntel Mariana, Moore Peter F, Avalos Julie, Young John D, Khan Dorothy, Donelson Randy, Pluhar G Elizabeth, Ohlfest John R, Wawrowsky Kolja, Lowenstein Pedro R, Castro Maria G Human Flt3L generates dendritic cells from canine peripheral blood precursors: implications for a dog glioma clinical trial. PloS one. 2010; 5(6): e11074.
Saghizadeh Mehrnoosh, Kramerov Andrei A, Yu Fu-Shin X, Castro Maria G, Ljubimov Alexander V Normalization of wound healing and diabetic markers in organ cultured human diabetic corneas by adenoviral delivery of c-Met gene. Investigative ophthalmology & visual science. 2010; 51(4): 1970-80.
Muhammad AKM, Candolfi M, King GD, Foulad D, Yagiz K, Mineharu Y, Kroeger K, Treuer KA, Nichols S, Sanderson NS, Lowenstein PR, Castro MG. Anti-glioma immunological memory in response to conditional cytotoxic/immune-stimulatory gene therapy: humoral and cellular immunity lead to tumor regression. Clinical Cancer Research 2009; In Press: .
Curtin JF, Liu N, Candolfi M, Xiong W, Assi H, Yagiz K, Edwards MR, Michelsen KS, Kroeger KM, Liu C, Muhammad AKM, Clark MC, Arditi M, Comin-Anduix B, Ribas A, Lowenstein PR, Castro MG HMGB1 mediates endogenous TLR2 activation and brain tumor regression. PLoS Medicine. 2009; 6(1): e10.
Candolfi M, Yagiz K, Foulad D, Alzadeh G, Tesarfreund M, Muhammad AKM, Puntel M, Kroeger KM, Liu C, Lee S, Curtin JF, King G, Lerner J, Sato K, Mineharu Y, Xiong W, Lowenstein PR, Castro MG Release of HMGB1 in response to pro-apoptotic glioma killing strategies: efficacy and neurotoxicity. Clinical Cancer Research. 2009; 15(13): 4401-4414.
Candolfi Marianela, Yagiz Kader, Foulad David, Alzadeh Gabrielle E, Tesarfreund Matthew, Muhammad A K M Ghulam, Puntel Mariana, Kroeger Kurt M, Liu Chunyan, Lee Sharon, Curtin James F, King Gwendalyn D, Lerner Jonathan, Sato Katsuaki, Mineharu Yohei, Xiong Weidong, Lowenstein Pedro R, Castro Maria G Release of HMGB1 in response to proapoptotic glioma killing strategies: efficacy and neurotoxicity. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009; 15(13): 4401-14.
King GD, Muhammad AK, Xiong W, Kroeger KM, Puntel M, Larocque D, Palmer D, Ng P, Lowenstein PR, Castro MG High-Capacity adenoviral vector-mediated 1 anti-glioma gene therapy in the presence of systemic anti-adenovirus immunity. Journal of Virology. 2008; 82(9): 4680-4684.
Curtin James F, Candolfi Marianela, Fakhouri Tamer M, Liu Chunyan, Alden Anderson, Edwards Matthew, Lowenstein Pedro R, Castro Maria G Treg depletion inhibits efficacy of cancer immunotherapy: implications for clinical trials. PloS one. 2008; 3(4): e1983.
Curtin JF, King GD, Barcia C, Liu C, Hubert FX, Guillonneau C, Josien R, Anegon I, Lowenstein PR, Castro MG. Fms-like tyrosine kinase 3 ligand recruits plasmacytoid dendritic cells to the brain. Journal of Immunology. 2006; 176(6): 3566-77.
Ali S, King GD, Curtin JF, Candolfi M, Xiong W, Liu C, Puntel M, Cheng Q, Prieto J, Ribas A, Kupiec-Weglinski J, van Rooijen N, Lassmann H, Lowenstein PR, Castro MG. Combined immunostimulation and conditional cytotoxic gene therapy provide long-term survival in a large glioma model. Cancer Research. 2005; 65(16): 7194-204.
Dewey RA, Morrissey G, Cowsill C, Stone D, Dodd NJF, Bolognani F, Southgate TD, Klatzmann D, Castro MG, Lowenstein PR. Chronic brain inflammation and persistent HSV1-TK expression in survivors of syngeneic glioma treated by adenovirus-mediated gene therapy: Implications for clinical trials. Nature Medicine. 1999; 5(11): 1256-1263.