Alemany, right you are..I didn't know he went back to Barcelona and make it his 'base' again..I think I better be more vigilant-g-
Juan Fueyo has to update his profile too-g-
utm-ext01a.mdacc.tmc.edu
Juan Fueyo-Margareto, MD
Research Interests:
Adenoviridae, gene therapy, glioma, antineoplastic agents
I am focusing on the development of novel approaches for the treatment of malignant gliomas. This research draws on recent discoveries in cellular and molecular biology. Since I joined M. D. Anderson more than 6 years ago, I have been studying the mechanisms of cell-cycle control and cell death that are abrogated in brain tumors. Preclinical data from my laboratory were used in part to develop a clinical trial of the transfer of p53 to brain tumors using adenoviral vectors. This work was done in collaboration with Drs. Candelaria Gomez-Manzano and W. K. Alfred Yung (this department). Working mainly on the p16/Rb (retinoblastoma)/E2F-1 pathway, my colleagues and I are also studying the role of p16 Rb, and E2F-1 as tumor suppressor genes in gliomas. Additionally, I am examining whether conventional chemotherapies for gliomas can be enhanced by combining them with gene therapies. Specifically, we are testing whether S-phase–inducer agents (including members of the E2F family of transcription factors) can create a favorable environment for anticancer agents that require cycling cells (including temozolomide) or that are S-phase specific (including irinotecan [CPT-11]). We hypothesize that gene-based approaches that help override the G2 arrest induced by conventional drugs will result in massive cell death. Adenoviral vectors can transfer exogenous genes to glioma xenografts in vivo; however, this system often does not transduce the number of cells needed to achieve a dramatic therapeutic effect. One way to effectively deliver genes is by using conditionally replicating adenoviruses that have a lytic phenotype, which is restricted to tumor cells. In this regard, Dr. Ramon Alemany, Ph.D. (Gene Therapy Center, University of Alabama at Birmimgham), Dr. Gomez-Manzano, and I were the first to identify a replication-competent adenovirus (delta-24) that cannot bind the Rb protein and that has a potent anticancer effect and low toxicity in quiescent normal cells. In collaboration with Drs. Frederick Lang, Jr. (Department of Neurosurgery), Gregory Fuller (Department of Pathology), and David Curiel (University of Alabama at Birmingham), the focus of my laboratory over the next 2 years will be on improving the anticancer effect of oncolytic adenoviruses and the translation of preclinical findings to the clinic.
Selected Publications
Fueyo J, Gomez-Manzano C, Alemany R, Lee PSY, McDonnell TJ, Mitlianga P, Shi Y-X, Levin VA, Yung WKA, Kyritsis AP. A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo. Oncogene 18:2-12, 2000
Fueyo J, Gomez-Manzano C, Yung WKA, Kyritsis AP. Targeting in gene therapy for gliomas. Arch Neurol 56:445-448, 1999
Fueyo J, Gomez-Manzano C, Yung WKA, Liu T-J, Alemany R, McDonnell TJ, Shi X, Levin VA, Kyritsis AP. Overexpression of E2F-1 in gliomas triggers caspase cascade and suppresses glioma growth in vitro and in vivo. Nat Med 4:685-690, 1998
Im S-A, Gomez-Manzano C, Fueyo J, Liu T-J, Ke LD, Kim J-S, Lee H-Y, Steck PA, Kyritsis AP, Yung WKA. Antiangiogenesis treatment for gliomas: Transfer of antisense-VEGF inhibits tumor growth in vivo. Cancer Res 59:895-900, 1999
Suzuki K, Fueyo J, Krasnykh V, Reynolds P, Curiel DT, Alemany R. A conditionally replicative adenovirus with enhanced infectivity shows improved oncolytic potency. Clin Cancer Res 7:120-126, 2001 |
