Research

The current focus of my research is to discover the molecular pathways underlying the growth patterns of malignant brain tumors using state-of-the-art RNA sequencing and Chip sequencing techniques.  My lab also studies the mechanisms which mediate, the interactions between cancer cells and the tumor immune microenvironment, in both experimental models in humans and patients suffering from malignant brain tumors.

The long term aim of my research program is to develop novel therapies for the treatment of malignant brain tumors based on the activation of both innate and adaptive immune responses against brain tumors. The current focus is to discover the cellular, molecular, and neuroanatomical basis underlying 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. To do so, we are probing how brain glioma cells migrate throughout the brain and eventually kill the hosts’ neurons and glial cells. Understanding the precise molecular basis of glioma tumor cell growth and invasive behavior, will uncover novel therapeutic targets aiming at inactivating the essential mechanisms used by tumors to grow and destroy normal brain tissue, and thus, kill the host. We are studying very early stages of tumor pattern formation using fluorescently labeled glioma cells in combination with advanced in vivo multiphoton imaging technologies. We are also developing endogenous models of brain tumors induced by genetic lesions encountered in human gliomas (e.g., PDGF, p53 KO, etc). The new information obtained is then channeled into the development of novel therapeutic strategies for malignant glioma.

Most recently we have discovered evidence that growing tumors are self-organized.  We believe this is akin to collective behaviors of animals (i.e. bird flocks)  Our data indicate that streams may increase tumor malignancy, increase the spreading of tumor cells, and favor invasion.  We are not studying the molecular basis of tumor self-organization in vivo and in vitro.

As PI or co-Investigator on several NIH-funded grants, I have set the basis for my long term research program to develop effective ways to translate robust preclinical ideas and data into clinical trials in patients suffering from gliomas. Our first approved IND (IND# 14574, approved by FDA on 4/7/11) for the treatment of primary gliomas with combined gene therapy using Adv-TK and Adv-Flt3L is now open. A broad background in neuropharmacology, neuroanatomy, neuroscience, neuro-oncology, neuroimmunology and medicine.  Medicine provides me with the ideal education and background to lead translational therapeutics. In addition, I am co-author of >260 peer-reviewed publications (PubMed) (H-index =45), and approximately 50 reviews, and book chapters. I am currently a member of the CSR College of NIH Reviewers and past-Chair of the Neurodegeneration and Biology of Glia (NDBG) Study Section. The overarching goals of my research program are to: (i) a thorough understanding of pattern formation by glioma and glioma stem cells and their therapeutic targeting, (ii) the discovery of novel molecular mechanisms used by glioma cells to migrate throughout individual compartments in the brain, (iii) an early phase translational clinical trials for patients suffering from highly aggressive malignant gliomas, and (iv) train the next generation of graduate students, post-doctoral scientists and physician/ scientists to lead these efforts in the future.

Areas of Interest

Brain Tumor Biology; Brain Tumor Therapeutics; Clinical Trials for Brain Tumors; Oncology Genomics; Mathematical Modeling of Cancer; Brain Tumor Neuroimmunology; Adaptive Innate Immune Response Against Glioma:  Experimental Genomic and Therapeutic Studies

Current Research Activity

• Endogeous glioma tumors:  use of genetic models of brain tumors and immune interaction to express genetic lesions encountered in human gliomas: role in tumorigenesis, invasion and self organization and immune interaction.
• Human Glioblastoma Stem Cells: human GBM stem cells isolated from human GBM tumors  stem cell culture isolation and characterization, genomics, transcriptome studies, selection of targets to study in animal genetic models.
• Self organization of brain tumors:  genomic and mathematical experimental modeling and their interactions.
• Role of Galectin 1 signaling in glioma models: role in cancer cells’ invasion, tumor progression, NK cells’ mediated cytotoxicity; and resistance to innate immunity.

Honors & Awards

• Co-Organizer, 2011 FASEB Summer Research Conference: “Translational Neuroimmunology: From Mechanisms to Therapeutics”, Carefree, Arizona, July 31-August 5, 2011
• Chair/Organizer, Methods Workshop: “Scientifically Significant Challenges for the Future of Translational Medicine: A View from the Trenches”, American Association for Cancer Research (AACR) 101^st Annual Meeting, Washington, DC, April 17-21, 2010
• Nominated Member, College of CSR Reviewers, Center for Scientific Review, National Institutes of Health, Bethesda, MD, from 2010
• Honorary Professor, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina, from 2010
• Elected to the Association of American Physicians (AAP), 2006
• Chair, Neural Disorders Committee, American Society for Gene and Cell Therapy (ASGCT); Member, Publications Committee, American Society for Gene and Cell Therapy (ASGCT), 2005
• Awarded “The Bram and Elaine Goldsmith Chair in Molecular Medicine and Gene Therapy”; Gene Therapeutics Research Institute, Cedars Sinai Medical Center; University of California at Los Angeles (UCLA), 2003
• Founding Editor, Current Gene Therapy, Bentham Science Publishers, P.O. Box 1673, 1200 R Hilversum, The Netherlands, selected & included in Index Medicus & MEDLINE, 2001
• Editor-in-Chief, Current Gene Therapy, Bentham Science Publishers, P.O. Box 1673, 1200 R Hilversum, The Netherlands, selected & included in Index Medicus & MEDLINE, 2001-2003
• Research Fellow, The Lister Institute of Preventive Medicine, “Gene therapy of human neurological disorders”, 1993-2001
• Awarded the ‘Brain Bursary’, to give the Annual Brain Bursary Lecture: “Gene therapy: molecular therapeutics for neurological diseases”. University College, London, UK, 4^th April, 2000
• Junior Research Fellow, Wolfson College, Oxford, 1988-1990.
• Visiting Fogarty Fellow, NINDS, Laboratory of Neurochemistry (Dr. Harold Gainer), National Institutes of Health, Bethesda, Maryland, USA, 1987.
• NIH Fogarty International Center Postdoctoral Fellowship, The Johns Hopkins University, School of Medicine, Baltimore, Department of Psychiatry (Dr. Joseph Coyle), MD, USA, 1984-1986.
• Biography included in “Who’s Who in America”, “Who’s Who in Medicine and Healthcare” and “Who’s Who in the World” published by Marquis, USA 2003 Editions.
• Biography included in “Who’s Who in American Education”, published by Marquis, USA 2004-2005 6th Edition
• Referenced in the “Who’s Who in Science”, 2001 Edition.
• First Prize. Best Dissertation submitted to the School of Medicine, University of Buenos Aires, Academic Year 1984.
• Bursary awarded from the Wellcome Trust and The British Pharmacological Society to assist the attendance to the 9^th International Congress of Pharmacology, London, July 29 - August 3, 1984. 

Credentials

Medical Degree

M.D. (Cum laude), School of Medicine, University of Buenos Aires, Argentina, 1981

Post-Graduate Degree

Ph.D. (Medical Sciences [Summa cum laude]) for thesis “Studies on the molecular basis of the mechanism of action of benzodiazepines in the pineal gland and the central nervous system”, School of Medicine, University of Buenos Aires, Argentina, 1984

Post-Doctoral Fellowship

Department of Psychiatry, The John Hopkins University School of Medicine, 1986

Post-Graduate Employment

Medical Research Council (MRC) Research Scientist, MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, Oxford University, United Kingdom, 1990

Board Certification/Licensures

Education Council for Foreign Medical Graduates (ECFMG) Certification, USA, 1983

State of Michigan, Board of Pharmacy, Research Laboratory Controlled Substance License, 2013