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P.R. Lowenstein, MD, PhD

Professor, Dept. of Neurosurgery,

Professor, Dept. of Cell and Developmental Biology

MSRB II, Room 4570

Department of Neurosurgery

University of Michigan School of Medicine

1150 West Medical Center Drive
Ann Arbor, MI 48109-5689

Phone (office) 734-764-0851

email: pedrol@umich.edu

Research Interests

The current focus of my research program is to discover the cellular, molecular, and mathematical basis underlying the growth patterns of malignant brain tumors, and the interactions between cancer cells with the tumor microenvironment, in both experimental models and in human patients suffering from malignant brain tumors. Based on our most recent discoveries we are now very interested in using nantotechnology to target the brain blood vessels surrounding brain tumors, as these would be the most important targets to destroy to reduce invasion of brain tumors.

I will bring to MNIMBS the establishment of joint ventures and new technological developments to create therapeutic approaches for the treatment of deadly brain tumors, by merging our most recent pathophysiological understanding of cancer growth and dispersion with nanotechnological approaches to target the structures we know are central to brain tumor invasion.  In summary, I can provide new disease models that can be targeted with nanotechnology.

Selected publications

  • Zirger JM, Puntel M, Bergeron J, Wibowo M, Moridzadeh R, Bondale N, Barcia C, Kroeger KM, Liu C, Castro MG, Lowenstein PR. (2012) 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 808-19. doi: 10.1038/mt.2011.243.
  • Candolfi M, Kroeger KM, Xiong W, Liu C, Puntel M, Yagiz K, Muhammad AG, Mineharu Y, Foulad D, Wibowo M, Assi H, Baker GJ, Lowenstein PR, Castro MG.  (2011) Targeted toxins for glioblastoma multiforme:  pre-clinical studies and clinical implementation.  Anticancer Agents Medicinal Chemistry 11:729-38.
  • Puntel M, Barrett R, Sanderson NS, Kroeger KM, Bondale N, Wibowo M, Kennedy S, Liu C, Castro MG, Lowenstein PR. (2011) Identification and visualization of CD8+ T cell mediated IFN-γ signaling in target cells during an antiviral immune response in the brain. PLoS One 6:e23523.
  • 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. Neoplasia13: 947-960.
  • 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: 4705-4718.
  • 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.  19:1793-801.
  • Xiong W, Candolfi M, Liu C, Muhammad AKM, Yagiz K, Puntel M, Moore PF, Avalos J, Young JD, Khan D, Donelson R, Pluhar GE, Ohlfest JR, Wawrowsky K, Lowenstein PR, Castro MG. (2010) Human Flt3L generates dendritic cells from canine peripheral blood precursors: implications for a dog glioma clinical trial. PLoS ONE 5:e11074.
  • Puntel M*, Muhammad AKMG*, Candolfi M, Salem A, Yagiz K, Farrokhi C, Kroeger KM, Xiong W, Curtin JF, Liu C, Bondale NS, Lerner J, Pechnick RN, Palmer D, Ng P, Lowenstein PR, Castro MG. (2010) A novel bi-cistronic 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. 84:6007-6017. * Co-first authors.
  • Pluhar GE, Grogan PG, Seiler C, Goulart M, Santacruz KS, Carlson C, Chen W, Olin MR, Lowenstein PR, Castro MG, Haines SJ, Ohlfest JR. (2010) Anti-tumor immune response correlates with neurological symptoms in a dog with spontaneous astrocytoma treated by gene and vaccine therapy.  Vaccine 28: 3371-3378.
  • Muhammad AKM, Puntel M, Candolfi M, Salem A, Yagiz K, Farrokhi C, Kroeger KM, Xiong W, Curtin JF, Liu C, Lawrence K, Bondale NS, Lerner J, Baker GJ, Foulad D, Pechnick RN, Palmer D, Ng P, Lowenstein PR, Castro MG. (2010) Study of the Efficacy, biodistribution and safety profile of therapeutic gutless adenovirus vectors as a prelude to a Phase 1 Clinical Trial for Glioblastoma. Clinical Pharmacology and Therapeutics 88:204-213.
  • Barcia C Jr, Gomez A, Gallego-Sanchez JM, Perez-Valles A, Castro MG, Lowenstein PR, Barcia C Sr, Herrero M-T. (2009) Infiltrating CTLs in human glioblastoma establish immunological synapses with tumorigenic cells. American Journal of Pathology 175(2):786-798 PMCID: PMC2716973.
  • Muhammad AKM, Candolfi M, King GD, Yagiz K, Foulad D, Mineharu Y, Kroeger K, Treuer KA, Nichols S, Sanderson NS, Yang JP, Khayznikov M, Van Rooijen N, Lowenstein PR, Castro MG. (2009) Anti-glioma immunological memory in response to conditional cytotoxic/immune-stimulatory gene therapy: humoral and cellular immunity lead to tumor regression Clinical Cancer Research 15:6113-6127.
  • Vit JP, Ohara PT, Sundberg C, Rubi B, Maechler P, Liu C, Puntel M, Lowenstein P, Castro M, Jasmin L. (2009) Adenovector GAD65 gene delivery into the rat trigeminal ganglion produces orofacial analgesia. Molecular Pain 5:42.
  • Barcia C, Wawrowsky K, Barrett RJ, Liu C, Castro MG, Lowenstein PR, (2008) In vivo polarization of IFN-g at Kupfer and non-Kupfer immunological synapses during the clearance of virally infected brain cells. The Journal of Immunology, 180(3)1344-1352. Portrayed on the cover; PMCID: PMC2629497.
  • Zirger JM, Barcia C, Liu C, Puntel M, Ngan M, Campbell I, Castro MG, Lowenstein PR, (2006) Rapid upregulation of IFNg-regulated and chemokine-mRNAs upon injection of 1 x 108 iu, but not lower doses of adenoviral vectors into the brain. The Journal of Virology 80:5655-5659. Portrayed on the cover
  • 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. (2005) Combined immune-stimulation and conditional cytotoxic gene therapy provide long-term survival in a large glioma model. Cancer Research 65:7194-7204.  Portrayed on the highlights section of Cancer Research.
  • Guillot C, Menoret S, Guillonneau C, Braudeau C, Castro MG, Lowenstein P, Anegon I. (2003) Active suppression of allogenic prolferative responses by dendritic cells after induction of long-term allograft survival by CTLA4Ig.  Blood 101: 3325-3333.

 

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