Pedro Lowenstein, M.D., Ph.D. Publications


ATRX loss in glioma results in dysregulation of cell-cycle phase transition and ATM inhibitor radio-sensitization.

Qin T, Mullan B, Ravindran R, Messinger D, Siada R, Cummings JR, Harris M, Muruganand A, Pyaram K, Miklja Z, Reiber M, Garcia T, Tran D, Danussi C, Brosnan-Cashman J, Pratt D, Zhao X, Rehemtulla A, Sartor MA, Venneti S, Meeker AK, Huse JT, Morgan MA, Lowenstein PR, Castro MG, Yadav VN, Koschmann C.
Cell Rep. 2022 Jan 11;38(2):110216.
doi: 10.1016/j.celrep.2021.110216


G-CSF secreted by mutant IDH1 glioma stem cells abolishes myeloid cell immunosuppression and enhances the efficacy of immunotherapy.

Alghamri MS, McClellan BL, Avvari RP, Thalla R, Carney S, Hartlage MS, Haase S, Ventosa M, Taher A, Kamran N, Zhang L, Faisal SM, Núñez FJ, Garcia-Fabiani MB, Al-Holou WN, Orringer D, Hervey-Jumper S, Heth J, Patil PG, Eddy K, Merajver SD, Ulintz PJ, Welch J, Gao C, Liu J, Núñez G, Hambardzumyan D, Lowenstein PR, Castro MG.
Sci Adv. 2021 Oct;7(40):eabh3243.
DOI: 10.1126/sciadv.abh3243

Uncovering Spatiotemporal Heterogeneity of High-Grade Gliomas: From Disease Biology to Therapeutic Implications 

Comba Andrea, Faisal Syed M., Varela Maria Luisa, Hollon Todd, Al-Holou Wajd N., Umemura Yoshie, Nunez Felipe J., Motsch Sebastien, Castro Maria G., Lowenstein Pedro R.
Front. Oncol., 05 Aug 2021
DOI: 10.3389/fonc.2021.703764

A novel miR1983-TLR7-IFNβ circuit licenses NK cells to kill glioma cells, and is under the control of galectin-1. 

Shah D, Comba A, Faisal SM, Kadiyala P, Baker GJ, Alghamri MS, Doherty R, Zamler D, Nuñez G, Castro MG, Lowenstein PR.
Oncoimmunology. 2021 Jun 28;10(1):1939601.
DOI: 10.1080/2162402X.2021.1939601

Genetic Alterations in Gliomas Remodel the Tumor Immune Microenvironment and Impact Immune-Mediated Therapies. 

Garcia-Fabiani MB, Haase S, Comba A, Carney S, McClellan B, Banerjee K, Alghamri MS, Syed F, Kadiyala P, Nunez FJ, Candolfi M, Asad A, Gonzalez N, Aikins ME, Schwendeman A, Moon JJ, Lowenstein PR, Castro MG.
Front Oncol. 2021 Jun 8;11:631037.
DOI: 10.3389/fonc.2021.631037

Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical Developments. 

Alghamri MS, McClellan BL, Hartlage MS, Haase S, Faisal SM, Thalla R, Dabaja A, Banerjee K, Carney SV, Mujeeb AA, Olin MR, Moon JJ, Schwendeman A, Lowenstein PR, Castro MG.
Front Pharmacol. 2021 May 18;12:680021.
DOI: 10.3389/fphar.2021.680021

Current Approaches for Glioma Gene Therapy and Virotherapy. 

Banerjee K, Núñez FJ, Haase S, McClellan BL, Faisal SM, Carney SV, Yu J, Alghamri MS, Asad AS, Candia AJN, Varela ML, Candolfi M, Lowenstein PR, Castro MG.
Front Mol Neurosci. 2021 Mar 11;14:621831.
DOI: 10.3389/fnmol.2021.621831

Targeting gliomas with STAT3-silencing nanoparticles

Kadiyala P, Gregory J, Lowenstein PR, Lahann J, Castro MG
Mol Cell Onco. 2021 Jan 31; 8(2) 
DOI: 10.1080/23723556.2020.1870647


Hemispherical Pediatric High-Grade Glioma: Molecular Basis and Therapeutic Opportunities. 

Haase S, Nuñez FM, Gauss JC, Thompson S, Brumley E, Lowenstein P, Castro MG.
Int J Mol Sci. 2020 Dec 17;21(24):E9654. 
DOI: 10.3390/ijms21249654

Immune-stimulatory (TK/Flt3L) gene therapy opens the door to a promising new treatment strategy against brainstem gliomas.

Faisal SM, Mendez FM, Nunez F, Castro MG, Lowenstein PR.
Oncotarget. 2020 Dec 15;11(50):4607-4612.
DOI: 10.18632/oncotarget.27834

Inhibition of 2-Hydroxyglutarate Elicits Metabolic-reprograming and Mutant IDH1 Glioma Immunity in Mice.

Kadiyala P, Carney SV, Gauss JC, Garcia-Fabiani MB, Haase S, Alghamri MS, Núñez FJ, Liu Y, Yu M, Taher AW, Nunez FM, Li D, Edwards MB, Kleer CG, Appelman H, Sun Y, Zhao L, Moon JJ, Schwendeman A, Lowenstein PR, Castro MG.
J Clin Invest. 2020 Dec 17:139542.
DOI: 10.1172/JCI139542

Genetically Engineered Mouse Model of Brainstem High-Grade Glioma.

Nunez FM, Gauss JC, Mendez FM, Haase S, Lowenstein PR, Castro MG.
STAR Protoc. 2020 Nov 25;1(3):100165.
DOI: 10.1016/j.xpro.2020.100165

Systemic brain tumor delivery of synthetic protein nanoparticles for glioblastoma therapy.

Gregory JV, Kadiyala P, Doherty R, Cadena M, Habeel S, Ruoslahti E, Lowenstein PR, Castro MG, Lahann J.
Nat Commun. 2020 Nov 10;11(1):5687.
DOI: 10.1038/s41467-020-19225-7

An Optimized Protocol for In Vivo Analysis of Tumor Cell Division in a Sleeping Beauty-Mediated Mouse Glioma Model.

Garcia-Fabiani MB, Kadiyala P, Lowenstein PR, Castro MG.
STAR Protoc. 2020 Sep 18;1(2):100044.
DOI: 10.1016/j.xpro.2020.100044

Synthetic High-density Lipoprotein Nanodiscs for Personalized Immunotherapy Against Gliomas.

Scheetz L, Kadiyala P, Sun X, Son S, Hassani Najafabadi A, Aikins M, Lowenstein PR, Schwendeman A, Castro MG, Moon JJ.
Clin Cancer Res. 2020 Aug 15;26(16):4369-4380.
DOI: 10.1158/1078-0432.CCR-20-0341

Glioblastoma Utilizes Fatty Acids and Ketone Bodies for Growth Allowing Progression during Ketogenic Diet Therapy.

Sperry J, Condro MC, Guo L, Braas D, Vanderveer-Harris N, Kim KKO, Pope WB, Divakaruni AS, Lai A, Christofk H, Castro MG, Lowenstein PR, Le Belle JE, Kornblum HI.
iScience. 2020 Aug 13;23(9):101453.
DOI: 10.1016/j.isci.2020.101453

Therapeutic Efficacy of Immune Stimulatory Thymidine Kinase and fms-like Tyrosine Kinase 3 Ligand (TK/Flt3L) Gene Therapy in a Mouse Model of High-Grade Brainstem Glioma.

Mendez F, Kadiyala P, Nunez FJ, Carney S, Nunez FM, Gauss JC, Ravindran R, Pawar S, Edwards M, Garcia-Fabiani MB, Haase S, Lowenstein PR, Castro MG.
Clin Cancer Res. 2020 Aug 1;26(15):4080-4092.
DOI: 10.1158/1078-0432.CCR-19-3714

Purine metabolism regulates DNA repair and therapy resistance in glioblastoma.

Zhou W, Yao Y, Scott AJ, Wilder-Romans K, Dresser JJ, Werner CK, Sun H, Pratt D, Sajjakulnukit P, Zhao SG, Davis M, Nelson BS, Halbrook CJ, Zhang L, Gatto F, Umemura Y, Walker AK, Kachman M, Sarkaria JN, Xiong J, Morgan MA, Rehemtualla A, Castro MG, Lowenstein P, Chandrasekaran S, Lawrence TS, Lyssiotis CA, Wahl DR.
Nat Commun. 2020 Jul 30;11(1):3811.
DOI: 10.1038/s41467-020-17512-x

Immunotherapy for gliomas: shedding light on progress in preclinical and clinical development.

Garcia-Fabiani MB, Ventosa M, Comba A, Candolfi M, Nicola Candia AJ, Alghamri MS, Kadiyala P, Carney S, Faisal SM, Schwendeman A, Moon JJ, Scheetz L, Lahann J, Mauser A, Lowenstein PR, Castro MG.
Expert Opin Investig Drugs. 2020 Jul;29(7):659-684.
DOI: 10.1080/13543784.2020.1768528

Fyn tyrosine kinase, a downstream target of receptor tyrosine kinases, modulates antiglioma immune responses.

Comba A, Dunn PJ, Argento AE, Kadiyala P, Ventosa M, Patel P, Zamler DB, Núñez FJ, Zhao L, Castro MG, Lowenstein PR.
Neuro Oncol. 2020 Jun 9;22(6):806-818.
DOI: 10.1093/neuonc/noaa006

Erratum: Fyn tyrosine kinase, a downstream target of receptor tyrosine kinases, modulates antiglioma immune responses.

Comba A, Dunn PJ, Argento AE, Kadiyala P, Ventosa M, Patel P, Zamler DB, Nunez FJ, Zhao L, Castro MG, Lowenstein PR.
Neuro Oncol. 2020 May 19:noaa063.
DOI: 10.1093/neuonc/noaa063

Self-organization in brain tumors: How cell morphology and cell density influence glioma pattern formation.

Jamous S, Comba A, Lowenstein PR, Motsch S.
PLoS Comput Biol. 2020 May 7;16(5):e1007611.
DOI: 10.1371/journal.pcbi.1007611

Laser Capture Microdissection of Glioma Subregions for Spatial and Molecular Characterization of Intratumoral Heterogeneity, Oncostreams, and Invasion.

Comba A, Dunn PJ, Kish PE, Kadiyala P, Kahana A, Castro MG, Lowenstein PR.
J Vis Exp. 2020 Apr 12;(158):10.3791/60939.
DOI: 10.3791/60939

Tumor mutational burden predicts survival in patients with low-grade gliomas expressing mutated IDH1.

Alghamri MS, Thalla R, Avvari RP, Dabaja A, Taher A, Zhao L, Ulintz PJ, Castro MG, Lowenstein PR.
Neurooncol Adv. 2020 Mar 27;2(1):vdaa042.
DOI: 10.1093/noajnl/vdaa042

Prospects of biological and synthetic pharmacotherapies for glioblastoma.

Altshuler DB, Kadiyala P, Nuñez FJ, Nuñez FM, Carney S, Alghamri MS, Garcia-Fabiani MB, Asad AS, Nicola Candia AJ, Candolfi M, Lahann J, Moon JJ, Schwendeman A, Lowenstein PR, Castro MG.
Expert Opin Biol Ther. 2020 Mar;20(3):305-317.
DOI: 10.1080/14712598.2020.1713085

Epigenetic reprogramming and chromatin accessibility in pediatric diffuse intrinsic pontine gliomas: a neural developmental disease.

Mendez FM, Núñez FJ, Garcia-Fabiani MB, Haase S, Carney S, Gauss JC, Becher OJ, Lowenstein PR, Castro MG.
Neuro Oncol. 2020 Feb 20;22(2):195-206.
DOI: 10.1093/neuonc/noz218

Isolation and characterization of immune cells from the tumor microenvironment of genetically engineered pediatric high-grade glioma models using the sleeping beauty transposon system.

Garcia-Fabiani MB, Comba A, Kadiyala P, Haase S, Núñez FJ, Altshuler D, Lowenstein PR, Castro MG.
Methods Enzymol. 2020;632:369-388.
DOI: 10.1016/bs.mie.2019.05.023

Functional assay to assess T-cell inhibitory properties of myeloid derived suppressor cells (MDSCs) isolated from the tumor microenvironment of murine glioma models.

Alghamri MS, Kamran N, Kadiyala P, Lowenstein PR, Castro MG.
Methods Enzymol. 2020;632:215-228.
DOI: 10.1016/bs.mie.2019.05.047

Functional characterization of tumor antigen-specific T-cells isolated from the tumor microenvironment of sleeping beauty induced murine glioma models.

Alghamri MS, Núñez FJ, Kamran N, Carney S, Altshuler D, Lowenstein PR, Castro MG.
Methods Enzymol. 2020;631:91-106.
DOI: 10.1016/bs.mie.2019.05.032


Engineering patient-specific cancer immunotherapies.

Scheetz L, Park KS, Li Q, Lowenstein PR, Castro MG, Schwendeman A, Moon JJ.
Nat Biomed Eng. 2019 Oct;3(10):768-782.
DOI: 10.1038/s41551-019-0436-x

High-Density Lipoprotein-Mimicking Nanodiscs for Chemo-immunotherapy against Glioblastoma Multiforme.

Kadiyala P, Li D, Nuñez FM, Altshuler D, Doherty R, Kuai R, Yu M, Kamran N, Edwards M, Moon JJ, Lowenstein PR, Castro MG, Schwendeman A.
ACS Nano. 2019 Feb 26;13(2):1365-1384.
DOI: 10.1021/acsnano.8b06842

IDH1-R132H acts as a tumor suppressor in glioma via epigenetic up-regulation of the DNA damage response.

Núñez FJ, Mendez FM, Kadiyala P, Alghamri MS, Savelieff MG, Garcia-Fabiani MB, Haase S, Koschmann C, Calinescu AA, Kamran N, Saxena M, Patel R, Carney S, Guo MZ, Edwards M, Ljungman M, Qin T, Sartor MA, Tagett R, Venneti S, Brosnan-Cashman J, Meeker A, Gorbunova V, Zhao L, Kremer DM, Zhang L, Lyssiotis CA, Jones L, Herting CJ, Ross JL, Hambardzumyan D, Hervey-Jumper S, Figueroa ME, Lowenstein PR, Castro MG.
Sci Transl Med. 2019 Feb 13;11(479):eaaq1427.
DOI: 10.1126/scitranslmed.aaq1427

Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures.

Núñez FJ, Mendez FM, Garcia-Fabiani MB, Pardo J, Edwards M, Lowenstein PR, Castro MG.
J Vis Exp. 2019 Jan 9;(143):10.3791/58931.
DOI: 10.3791/58931


Molecular ablation of tumor blood vessels inhibits therapeutic effects of radiation and bevacizumab.

Yadav VN, Altshuler D, Kadiyala P, Zamler D, Comba A, Appelman H, Dunn P, Koschmann C, Castro MG, Löwenstein PR.
Neuro Oncol. 2018 Sep 3;20(10):1356-1367.
DOI: 10.1093/neuonc/noy055

Mutant ATRX: uncovering a new therapeutic target for glioma.

Haase S, Garcia-Fabiani MB, Carney S, Altshuler D, Núñez FJ, Méndez FM, Núñez F, Lowenstein PR, Castro MG.
Expert Opin Ther Targets. 2018 Jul;22(7):599-613. 
DOI: 10.1080/14728222.2018.1487953

Immature myeloid cells in the tumor microenvironment: Implications for immunotherapy.

Kamran N, Chandran M, Lowenstein PR, Castro MG.
Clin Immunol. 2018 Apr;189:34-42. 
DOI: 10.1016/j.clim.2016.10.008

Evolutionary basis of a new gene- and immune-therapeutic approach for the treatment of malignant brain tumors: from mice to clinical trials for glioma patients.

Lowenstein PR, Castro MG.
Clin Immunol. 2018 Apr;189:43-51.
DOI: 10.1016/j.clim.2017.07.006

Current state and future prospects of immunotherapy for glioma.

Kamran N, Alghamri MS, Nunez FJ, Shah D, Asad AS, Candolfi M, Altshuler D, Lowenstein PR, Castro MG.
Immunotherapy. 2018 Feb 1;10(4):317-339.
DOI: 10.2217/imt-2017-0122

Native Chromatin Immunoprecipitation Using Murine Brain Tumor Neurospheres.

Mendez FM, Núñez FJ, Zorrilla-Veloz RI, Lowenstein PR, Castro MG.
J Vis Exp. 2018 Jan 29;(131):57016.
DOI: 10.3791/57016


Melanoma induced immunosuppression is mediated by hematopoietic dysregulation.

Kamran N, Li Y, Sierra M, Alghamri MS, Kadiyala P, Appelman HD, Edwards M, Lowenstein PR, Castro MG.
Oncoimmunology. 2017 Dec 14;7(3):e1408750.
DOI: 10.1080/2162402X.2017.1408750

Multi-focal sequencing of a diffuse intrinsic pontine glioma establishes PTEN loss as an early event.

Koschmann C, Farooqui Z, Kasaian K, Cao X, Zamler D, Stallard S, Venneti S, Hervey-Jumper S, Garton H, Muraszko K, Franchi L, Robertson PL, Leonard M, Opipari V, Castro MG, Lowenstein PR, Chinnaiyan A, Mody R.
NPJ Precis Oncol. 2017 Sep 14;1(1):32.
DOI: 10.1038/s41698-017-0033-y

Single vs. combination immunotherapeutic strategies for glioma.

Chandran M, Candolfi M, Shah D, Mineharu Y, Yadav VN, Koschmann C, Asad AS, Lowenstein PR, Castro MG.
Expert Opin Biol Ther. 2017 May;17(5):543-554.
DOI: 10.1080/14712598.2017.1305353

Survival and Proliferation of Neural Progenitor-Derived Glioblastomas Under Hypoxic Stress is Controlled by a CXCL12/CXCR4 Autocrine-Positive Feedback Mechanism.

Calinescu AA, Yadav VN, Carballo E, Kadiyala P, Tran D, Zamler DB, Doherty R, Srikanth M, Lowenstein PR, Castro MG.
Clin Cancer Res. 2017 Mar 1;23(5):1250-1262.
DOI: 10.1158/1078-0432.CCR-15-2888

Mutated Chromatin Regulatory Factors as Tumor Drivers in Cancer.

Koschmann C, Nunez FJ, Mendez F, Brosnan-Cashman JA, Meeker AK, Lowenstein PR, Castro MG.
Cancer Res. 2017 Jan 15;77(2):227-233.
DOI: 10.1158/0008-5472.CAN-16-2301

Immunosuppressive Myeloid Cells' Blockade in the Glioma Microenvironment Enhances the Efficacy of Immune-Stimulatory Gene Therapy.

Kamran N, Kadiyala P, Saxena M, Candolfi M, Li Y, Moreno-Ayala MA, Raja N, Shah D, Lowenstein PR, Castro MG.
Mol Ther. 2017 Jan 4;25(1):232-248.
DOI: 10.1016/j.ymthe.2016.10.003


CXCR4 increases in-vivo glioma perivascular invasion, and reduces radiation induced apoptosis: A genetic knockdown study.

Yadav VN, Zamler D, Baker GJ, Kadiyala P, Erdreich-Epstein A, DeCarvalho AC, Mikkelsen T, Castro MG, Lowenstein PR.
Oncotarget. 2016 Dec 13;7(50):83701-83719. 
DOI: 10.18632/oncotarget.13295

Characterizing and targeting PDGFRA alterations in pediatric high-grade glioma.

Koschmann C, Zamler D, MacKay A, Robinson D, Wu YM, Doherty R, Marini B, Tran D, Garton H, Muraszko K, Robertson P, Leonard M, Zhao L, Bixby D, Peterson L, Camelo-Piragua S, Jones C, Mody R, Lowenstein PR, Castro MG.
Oncotarget. 2016 Oct 4;7(40):65696-65706.
DOI: 10.18632/oncotarget.11602

Recent advances and future of immunotherapy for glioblastoma.

Kamran N, Calinescu A, Candolfi M, Chandran M, Mineharu Y, Asad AS, Koschmann C, Nunez FJ, Lowenstein PR, Castro MG.
Expert Opin Biol Ther. 2016 Oct;16(10):1245-64. 
DOI: 10.1080/14712598.2016.1212012

Multiple Expressed Endogenous Glioma Epitopes as Novel Vaccines for Gliomas.

Lowenstein PR, Castro MG.
Clin Cancer Res. 2016 Oct 1;22(19):4760-4762. 
DOI: 10.1158/1078-0432.CCR-16-1477

Reversibility of glioma stem cells' phenotypes explains their complex in vitro and in vivo behavior: Discovery of a novel neurosphere-specific enzyme, cGMP-dependent protein kinase 1, using the genomic landscape of human glioma stem cells as a discovery tool.

Wilson TJ, Zamler DB, Doherty R, Castro MG, Lowenstein PR.
Oncotarget. 2016 Sep 27;7(39):63020-63041.
DOI: 10.18632/oncotarget.11589

Preclinical Efficacy and Safety Profile of Allometrically Scaled Doses of Doxycycline Used to Turn "On" Therapeutic Transgene Expression from High-Capacity Adenoviral Vectors in a Glioma Model.

VanderVeen N, Raja N, Yi E, Appelman H, Ng P, Palmer D, Zamler D, Dzaman M, Lowenstein PR, Castro MG.
Hum Gene Ther Methods. 2016 Jun;27(3):98-111.
DOI: 10.1089/hgtb.2015.168

ATRX mutations and glioblastoma: Impaired DNA damage repair, alternative lengthening of telomeres, and genetic instability.

Koschmann C, Lowenstein PR, Castro MG.
Mol Cell Oncol. 2016 Apr 27;3(3):e1167158. 
DOI: 10.1080/23723556.2016.1167158

Natural killer cells require monocytic Gr-1(+)/CD11b(+) myeloid cells to eradicate orthotopically engrafted glioma cells.

Baker GJ, Chockley P, Zamler D, Castro MG, Lowenstein PR.
Oncoimmunology. 2016 Mar 16;5(6):e1163461.
DOI: 10.1080/2162402X.2016.1163461

ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma.

Koschmann C, Calinescu AA, Nunez FJ, Mackay A, Fazal-Salom J, Thomas D, Mendez F, Kamran N, Dzaman M, Mulpuri L, Krasinkiewicz J, Doherty R, Lemons R, Brosnan-Cashman JA, Li Y, Roh S, Zhao L, Appelman H, Ferguson D, Gorbunova V, Meeker A, Jones C, Lowenstein PRCastro MG.
Sci Transl Med. 2016 Mar 2;8(328):328ra28.
DOI: 10.1126/scitranslmed.aac8228

Gene Therapy for the Treatment of Neurological Disorders: Central Nervous System Neoplasms.

Kamran N, Candolfi M, Baker GJ, Ayala MM, Dzaman M, Lowenstein PR, Castro MG.
Methods Mol Biol. 2016;1382:467-82. 
DOI: 10.1007/978-1-4939-3271-9_31

The Long and Winding Road: From the High-Affinity Choline Uptake Site to Clinical Trials for Malignant Brain Tumors.

Lowenstein PR, Castro MG.
Adv Pharmacol. 2016;76:147-73.
DOI: 10.1016/bs.apha.2016.03.002