Pedro R. Lowenstein, M.D., Ph.D., is a professor of neurosurgery and cell and developmental biology at the University of Michigan. He received his M.D. and Ph.D from the School of Medicine, University of Buenos Aires, Argentina, and has held research positions at Johns Hopkins, the National Institutes of Health and Oxford University (United Kingdom). He then became professor of molecular medicine and gene therapy at the School of Medicine, University of Manchester, England, where he pioneered the development and implementation of a novel immunotherapy approach to treat malignant brain cancers in adults and children.
In 2001, Dr. Lowenstein became a professor of molecular and medical pharmacology at the University of California, Los Angeles, before moving to the University of Michigan Medical School in 2011, where he now holds the Richard Schneider Collegiate Professorship in the Department of Neurosurgery.
The focus of Dr. Lowenstein’s research program is to discover the cellular, molecular, and structural basis of malignant glioma growth and invasion, the role of glioblastoma (GBM) derived micro RNAs into the tumor microenvironment, GBM stem cell microbiology, tumor derived double-stranded DNA and the STING signaling pathway. Dr. Lowenstein is pioneering the implementation of patient derived xenograft models using tissue derived from human glioma patients, including pediatric patients with diffuse intrinsic brainstem glioma (DIPG). His team is establishing patient derived GBM cell cultures in the lab to test novel small molecule chemotherapeutics which can be immediately translated to the clinic.
Dr. Lowenstein is also interested in understanding glioma-immune interactions in order to develop novel therapies to treat patients suffering from this rapidly progressive disease. A novel strategy to combat brain tumors that reprograms the brain immune system (endogenous immunotherapy) to attack and destroy malignant brain tumor cells, recently approved by the FDA, is now being tested in human clinical trials in the Department of Neurosurgery at the University of Michigan.
Maria G. Castro, Ph.D., is the R.C. Schneider Collegiate Professor of Neurosurgery and a professor of cell and developmental biology at the University of Michigan Medical School. She received her Ph.D. in biochemistry from the National University of LaPlata in Buenos Aires in 1986. Shortly after, she was awarded a Fogarty International Fellowship to continue her training as a postdoctoral fellow at the National Institutes of Health in Bethesda, Maryland. Dr. Castro held faculty positions at the University of Wales College of Cardiff, and was a professor of medicine at the University of Manchester, England. In 2001, she was appointed professor of molecular and medical pharmacology at the University of California, Los Angeles, School of Medicine with a joint appointment as professor of medicine at Cedars-Sinai Medical Center. Dr. Castro joined the University of Michigan in 2011 as a professor in the departments of Neurosurgery and Cell and Developmental Biology.
Dr. Castro is a world leader in glioma immune-microenvironment and development of novel anti-GBM immunotherapies. Her research focuses on uncovering the role of oncometabolites in the brain tumor microenvironment and epigenetic reprogramming. Her team is developing novel models of pediatric malignant glioma, including DIPG. She is aiming to use these genetically engineered murine models to uncover molecular mechanisms that mediate tumor progression and implement novel therapeutic approaches which will ultimately be translated to human clinical trials.
Dr. Castro’s team is also developing novel immunotherapies for primary and metastatic brain cancer, studying basic immune-biology mechanisms leading to clinical implementation. They are investigating the role of the tumor immune-microenvironment in tumor progression and response to therapeutics; crosstalk between cancer cells and hematopoietic stem/progenitor cells, and mechanisms affecting the migration of immune cells from peripheral lymphoid organs to the tumor microenvironment. Her innovative work has led to an FDA approved gene therapy phase 1 clinical trial for malignant brain cancer which is ongoing in the University of Michigan Department of Neurosurgery.
Xing Fan, M.D., Ph.D., is an associate professor of neurosurgery and cell and developmental biology at the University of Michigan Medical School. Dr. Fan received his M.D. in 1994 and then did three years of neurosurgical training at Tianjin Medical University in China. He later completed his Ph.D. at the University of Navarra in Spain in 2002. Subsequently, he came to the United States for his postdoctoral fellowship at Johns Hopkins University. Dr. Fan joined the University of Michigan faculty in 2008 to establish his own laboratory.
Dr. Fan is an international expert on developmental signaling pathways in brain cancer stem cells. He has discovered that the Notch pathway blockade by gamma-secretase inhibitor (GSI) depletes cancer stem like cells in both medulloblastoma — the most common malignant brain tumor in children — and glioblastoma — the most common malignant brain tumor in adults. Based on his published data, the National Cancer Institute has launched phase I clinical trials using GSI to treat medulloblastoma and malignant gliomas in 24 institutions across the country. The first report shows that 24 percent of malignant glioma patients have stabilized disease for more than four months after GSI treatment. A phase II clinical trial combining GSI with chemotherapeutic drug temozolomide is now underway. His current research focuses on developing additional therapeutic strategies to target cancer stem cells in medulloblastoma, glioblastoma and Diffuse Intrinsic Pontine Glioma (DIPG).
Dr. Fan has received many prestigious national awards for his brain tumor research and his work is currently funded by several private foundation grants and NIH R01 grants. As a national leader in brain tumor research, Dr. Fan has been invited to give lectures at many national and international conferences, as well as prestigious institutions including Johns Hopkins University, the University of Texas M.D. Anderson Cancer Center, Ohio State University, and Harvard University. Dr. Fan has made an indelible contribution to the brain tumor research community. He has reviewed manuscripts for 17 renowned peer-reviewed journals and is an editorial board member for the American Journal of Stem Cells. He has been reviewing grants for national and international agencies, including NIH study sections, Samantha Dickson Brain Tumour Trust in the UK, Spanish National Evaluation and Foresight Agency in Spain, Canada Research Chairs Program in Canada and Swiss Cancer League in Switzerland.
Daniel A. Orringer, M.D., is an assistant professor of neurological surgery at the University of Michigan Medical School. After attending Cornell University, Dr. Orringer earned his medical degree from The Ohio State University in 2004. His residency took place at the U-M, followed by a fellowship at Brigham and Women’s Hospital. Upon completion of his residency he had published more than 20 peer-reviewed publications and was awarded two institutional teaching awards and a leadership award.
During brain tumor surgery, precision is key. Removing healthy tissue can cause neurologic deficits; leaving tumor behind can allow cancer to spread and treatment to fail. Consequently, optimal surgical results are achieved in only one-third of glioblastoma patients. To help surgeons accurately distinguish between tumor and normal tissue, Dr. Orringer and his colleagues have developed an entirely new imaging technique called Stimulated Raman Scattering (SRS) microscopy for visualizing cancer cells in the brain during surgery.
SRS microscopy enables rapid, high-resolution, imaging of tissues based on the distribution of lipids, proteins, and DNA, eliminating the need for dye to visualize tissue architecture. Much like MRI, SRS microscopy can generate images of the human brain without the need for removing or processing tissue. However, unlike MRI, SRS microscopy can generate images on a microscopic level where there is a clear difference between tumor and normal brain.
Dr. Orringer’s research, featured on a recent cover of Science Translational Medicine and reported by news outlets across the globe, demonstrates for the first time that it is possible to use a laboratory-style SRS microscope to guide brain tumor surgery. SRS microscopy is expected to deliver the best possible surgical results, prolonging and improving quality of life for patients afflicted with glioblastoma. It may also improve the safety and accuracy of other types of surgeries in which tumor boundaries are visually indistinct.
Dr. Orringer received the prestigious Young Clinician Investigator Award for 2013-14 from the American Association of Neurosurgeons for his groundbreaking work on SRS microscopy imaging.