Pedro R. Lowenstein, MD, Ph.D. is a Professor of Neurosurgery and Cell and Developmental Biology at the University of Michigan. He received his M.D./Ph.D. from the School of Medicine, University of Buenos Aires, Argentina. The focus of his 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. Another focus of his research program aims to harness the new information obtained on the mechanisms of tumor growth for therapeutic intent. Specifically, he will utilize nanoparticles targeted to peri-tumoral blood vessels to block GBM invasion. Recent work discovered that both rodent and human glioma cells and glioma stem cells disperse from the primary tumor inoculum by growing along peri-tumoral blood vessels. We predict that eliminating the vessels which support GBM growth and invasion will elicit long term survival of tumor bearing animal, and thus, this approach could become a future therapy for GBM. The long term goal will be to translate this strategy into early phase clinical trials. In this regard, Dr. Lowenstein’s pioneering work in gene therapy for glioblastoma multiforme has been approved by the FDA and a Phase I clinical trial will commence at the University of Michigan imminently.
Areas of Interest
- High-Grade Gliomas
- Antigen Processing/Presentation
- Cell Homing/Trafficking
- Cytokine Networks
- Innate Immunity
- T-Cell Activation
- Viral Infections in the Brain
- Gene Delivery
- Diffuse Intrinsic Pontine Glioma (DIPG)
- Cell Signaling
- Immune Suppression
- T-Cell Biology
- Animal Models of Disease
- Vaccine Development
- Gene Therapy
The focus of Dr. Lowenstein's research program is to discover the cellular, molecular, and mathematical basis underlying the growth patterns of malignant brain tumors, the molecular and cellular mechanisms that mediate tumor immune escape and the interactions between cancer cells with the tumor microenvironment, in both experimental models and in human patients suffering from malignant brain tumors. His group has shown that galectin-1 knockdown in cancer cells causes the eradication of intracranial glioma in RAG1-/- mice lacking mature B- and T-cells by sensitizing tumor cells to NK cytotoxicity. Conversely, in NK cell depleted RAG1-/- mice, and severely immunocompromised NOD-scid IL2Rg null mice, galectin-1 deficient glioma cells progress killing the host with 100% efficiency. C57BL/6J mice with intact B- and T-cells enable galectin-1 deficient glioma growth only when NK cells are depleted. The data indicate that adaptive immunity is not required for galectin-1 deficient glioma rejection. Investigation is underway into therapeutic galectin-1 suppression to improve outcomes in patient survival by heightening NK immune surveillance.
Current Research Activity
- “Endogeous glioma models: use of lentivirus vectors to express genetic lesions encountered in human tumors: role in tumorigenesis, invasion and the immune microenvironment.”
- “Role of Galectin 1 signaling in glioma models: role in cancer cells’ invasion, tumor progression and NK cells’ mediated cytotoxicity.”
- “Human Glioblastoma Stem Cells: investigations in human GBM specimens and isolated human GBM stem cells in culture. Immune mediated mechanisms in GBM stem cells’ migration.”
- “Role of angiogenesis in brain tumor invasion and immune cell migration: molecular and cellular mechanisms”.
Honors & Awards
- Member, College of CSR Reviewers, Center for Scientific Review, National Institutes of Health, Bethesda, MD, from 2010.
- Richard Schneider Collegiate Professor of Neurosurgery, Department of Neurosurgery, University of Michigan, School of Medicine, October 2013.
- Co-Director of Neuro-Oncology Program, Rogel Cancer Center, University of Michigan, June 2015.
- Elected Fellow, The American Association for the Advancement of Science (AAAS), 2018.
- Elected Member, The Latin American Academy of Sciences (ACAL), Caracas, Venezuela, 2020.
M.D. (Cum laude), School of Medicine, University of Buenos Aires, Argentina, 1981
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
Department of Psychiatry, The John Hopkins University School of Medicine, 1986
Medical Research Council (MRC) Research Scientist, MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, Oxford University, United Kingdom, 1990
Education Council for Foreign Medical Graduates (ECFMG) Certification, USA, 1983
State of Michigan, Board of Pharmacy, Research Laboratory Controlled Substance License, 2013
A complete list of Dr. Lowenstein's grant support is located here.
A complete list of Dr. Lowenstein's recent publications is located here.