Research

Our clinical faculty maintain research interests within their fields and are complemented by a large group of dedicated research faculty, positioning the department among the leaders in the nation for federal and extramural research funding. The environment at Michigan can support research at the highest level.

Research is conducted in the Crosby Neurosurgical Research Laboratories, the Castro & Lowenstein Translational Neuro-Oncology Laboratories, and in our various clinical areas.

Crosby Neurosurgical Laboratories

The Crosby Neurosurgical Laboratories are named after famed neuroanatomist, Dr. Elizabeth Crosby. The laboratories have two main areas of research focus, cerebrovascular disease and CNS tumors.

The cerebrovascular focus, with Drs. Richard Keep, Guohua Xi, Ya Hua, Aditya Pandey, Oren Sagher and Jianming Xiang, centers on elucidating mechanisms of brain injury in hemorrhagic and ischemic stroke, and the effects of neurological disease on the blood-brain barrier. They use in vitro, small animal, and large animal models of intracerebral, subarachnoid and intraventricular hemorrhage, as well as cerebral ischemia.  Much work has focused on the role of clot-derived factors in brain injury after cerebral hemorrhage and the studies led by Dr. Guohua Xi formed the basis of the recent Phase II clinical trial of an iron chelator, deferoxamine, in intracerebral hemorrhage.

The CNS tumor focus, with Drs. Xing Fan, Nicholas Szerlip and Alexandra Calinescu, centers on the role of cancer stem cells in glioblastoma and medullobastoma, the stem cell vascular niche, developing new therapies for spine metastatic cancers, and engineering stem cells as inflammatory sensors and vehicles for delivering therapeutics for glioblastoma. They use in vitro and mouse models, as well as human tumors.  The preclinical work of Dr. Xing Fan contributed to current clinical trials of NOTCH inhibitors targeting cancer stem cells in brain tumors.

The Crosby Laboratories, which cover about 6,000 square feet, are well equipped for both in vitro and in vivo work.  They are mostly housed in the A. Alfred Taubman Biomedical Sciences Research Building at the University of Michigan. This building houses numerous core facilities, including the Center for Molecular Imaging (small animal MRI and optical imaging) and the Microscope and Image Analysis Facility.

Castro & Lowenstein Translational Neuro-Oncology Laboratory

The focus the Castro & Lowenstein Lab is to discover the cellular, molecular, and mathematical basis underlying the growth patterns of malignant brain tumors (glioma, GBM), and the interactions between cancer cells with the tumor microenvironment, in both experimental models and in human patients.

Understanding the precise molecular basis of glioma tumor cell growth and invasive behavior will uncover novel therapeutic targets aimed at inactivating the essential mechanisms used by tumors to grow and destroy normal brain tissue, and thus, kill the host.

This lab is also developing novel immunotherapies for primary and metastatic brain cancer. Research within the lab stems all the way from basic immunobiology mechanisms to translational immune-therapeutics.

Another active research area is related to the tumor immune-microenvironment:  its role in tumor progression and response to therapeutics; cross talk between cancer cells and hematopoietic stem/progenitor cells; and mechanisms affecting the migration of immune cells from peripheral lymphoid organs to the tumor microenvironment.

The Castro & Lowenstein Lab has recently focused research efforts on DNA repair pathways, the epigenetic regulation of cancer progression, uncovering the role of oncometabolites in the brain tumor microenvironment and in mediating the response to immunotherapies. To this end, novel rodent models are being developed of malignant brain cancer using in vivo gene transfer technologies. To accomplish this, the Sleeping Beauty Transposase System is being used to insert specific genetic lesions in the genome of stem cells lining the third ventricle. These genetically engineered murine models harboring genetic lesions present in the human disease have proven to be powerful platforms to uncover the molecular mechanisms that mediate tumor progression and implement novel immune-mediated gene and/or cell based therapeutic approaches. These approaches will lead to the development of novel therapeutic approaches and their implementation in Phase I clinical trials for GBM.

Pioneering work from the Castro & Lowenstein Lab has led to an FDA approved Phase I clinical trial for malignant brain cancer which is ongoing at the University of Michigan, Department of Neurosurgery.

Lab website:  http://castro-lowenstein.lab.medicine.umich.edu/

The Castro-Lowenstein clinical trial:   clinicaltrials.gov number NCT01811992,    http://clinicaltrials.gov/ct2/results?term=Lowenstein+AND+glioma&Search=Search.