Text Image: UM Medical School: Graduate Program in Immunology
Text Image: Faculty

Maria Castro, Ph.D.
R C Schneider Collegiate Professor of Neurosurgery
Professor of Cell and Developmental Biology

Current Research Activity

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.

a) “Role of brain tumor ligands in the differentiation and maturation of
myeloid hematopoietic precursor cells:  impact on anti-tumor immunity”. 

b) “The hematopoietic stem cell niche in brain cancer:  impact tumor progression on anti-tumor immunity”.

c) “Gutless adenovirus vectors encoding immune-stimulatory cytokines and conditional cytotoxic genes to develop anti-glioblastoma multiforme immunotherapies.”

d) “Role of RAGE signalling in glioblastoma multiforme preclinical in vivo models: impact on innate immunity.”

e) “Role of STAT3 signaling in anti-glioblastoma multiforme immunotherapies: role on dendritic cells’ vaccination efficacy, antigen presentation and effector T cells.”

f) “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.”

Recent Selected Publications

Candolfi M, Yagiz K, Wibowo M, Ahlzadeh G, Puntel M, Kamran N, Paran C, Ghiasi H, Lowenstein PR, Castro MG. (2014) Temozolomide does not impair gene therapy-mediated antitumor immunity in syngenic brain tumor models. Clinical Cancer Research. March 15, 2014: 20(6): 1555-65. Epub ahead of print February 5, 2014. Portrayed on the cover of the March, 2014 issue. PMCID: PMC3959570.

Assi H, Paran C, VanderVeen N, Savakus J, Doherty R, Petruzzella E, Hoeschele J, Appelman H, Raptis L, Mikkelsen T, Lowenstein PR, Castro MG. (2014) Pre-clinical characterization of signal transducer and activator of transcription 3 small molecule inhibitors for primary and metastatic brain cancer therapy. Journal of Pharmacology and Experimental Therapeutics, June, 2014, 349(3), 458-69.
Epub ahead of print April 2, 2014. PMCID: PMC4019317

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.

Candolfi M, King GD, Yagiz K, Curtin JF, Mineharu Y, Muhammad AG, Foulad D. Kroeger KM, Barnett N, Josien R, Lowenstein PR, and Castro, MG.  (2012) Plasmacytoid Dendritic Cells in the Tumor Microenvironment:  Immune Targets for Glioma Therapeutics. Neoplasia, 2012 Aug;14(8):757-70.  PMCID:  PMC3431182.

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.

Candolfi M, Curtin JF, Yagiz K, Assi H, Wibowo MK, Alzadeh GE, Foulad D, Muhammad AK, Salehi S, Keech N, Puntel M, Liu C, Sanderson NR, Kroeger KM, Dunn R, Martins G, Lowenstein PR, Castro MG. (2011) B cells are critical to T-cell-mediated antitumor immunity induced by a combined immune-stimulatory/conditionally cytotoxic therapy for glioblastoma. Neoplasia, 13(10), 947-960.  PMCID:  PMC3201571.

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.

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.

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.

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.

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.

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.

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.

Barcia C, Thomas CE, Curtin JF, King GD, Wawrowsky K, Candolfi M, Xiong WD, Liu C, Kroeger K, Boyer O, Kupiec-Weglinski J, Klatzmann D, Castro MG, Lowenstein PR. (2006) In Vivo mature immunological synapses forming SMACs mediate clearance of virally infected astrocytes from the brain. Journal of Experimental Medicine, 203:2095-2107.  Work portrayed on journal cover, highlighted in the journal; reviewed by Science, 313[issue 5790, August 25, 2006] p. 1020; reviewed by Cell [October 20, 2006], and Journal of Cell Biology [September 11, 2006]; cited in Faculty of 1000 Medicine.  PMCID: PMC1997281.

Iannacone M, Sitia G, Isogawa M, Marchese P, Castro MG, Lowenstein PR, Chisari FV, Ruggeri ZM, Guidotti LG (2005) Platelets mediate cytotoxic T lymphocyte-induced liver damage. Nature Medicine 11(11):1167-1169.  PMCID:  PMC2908083.

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