Neurosurgery and neuroscience research
Since its inception in 1996 the Henry Ford Neuroscience Institute has received more than $185 million in research funds and conducted more than 630 clinical trials. Currently more than 180 clinical trials are ongoing for patients with neurological diseases.
Marcia and Eugene Applebaum Laboratory of Invasion & Molecular Therapeutics (Tom Mikkelsen, M.D.)
Research is focused on acquiring molecular data from glioblastoma and other brain tumors to develop therapies tailored to each type of these highly aggressive tumors. Dr. Mikkelsen is one of the Co-directors Neurosurgery and Neuroscience Research of The Hermelin Brain Tumor Center. The Center’s Tissue Bank, one of the three largest in the world, includes more than 3,300 tissue specimens. These specimens are being used as a national resource to understand the basic mechanisms involved in development of brain tumors and to design new approaches to target treatment. Dr. Mikkelsen is also working on the NIH Cancer Genome Atlas (TCGA) project, started in 2007 to chart genomic changes in 20 different types of cancer, selected to study glioblastoma, the most deadly and common type of brain cancer. Among the leading brain tumor centers in the U.S., the Hermelin Brain Tumor Center contributed 40% of the 500 glioblastoma tissues collected for analysis by the NIH.
In addition to numerous clinical trials, Dr. Mikkelsen’s lab is also supported by individual private donors. Examples of those would be: The Indenbaum Preclinical Research Program - The characterization of driver mutations in brain tumors will help lead to development of new therapies targeted to each molecular subtype of brain cancer, and The Jeffries Family Personalized Clinical Trials Program. Since the molecular causes of tumor development and growth differ for each patient’s tumor, it is not surprising that clinical trials have failed to achieve significant improvements in the majority of tumors. This effort along with other national organizations such as ABC2 will develop a novel national clinical trials program under the Hermelin Center’s supervision to personalize the approach and likely lead to more agents approved and a remarkable improvement in care. The research group is currently taking advantage of the emerging technologies to acquire molecular data from glioblastoma and other brain tumors collected at the HBTC, in collaboration with academic centers that specialize in genomics and proteomics research. Because glioblastoma tumors are very heterogeneous, the efficacy of therapeutic interventions varies from patient to patient. The detailed molecular information from these tumors is the basis for the development of therapies tailored to attack each type of these highly aggressive tumors. In the past few years, we have been successfully culturing cancer stem cells from these tumors, which retain the genomic characteristics and can recreate the tumor in research animals. These remarkable developments now allow us to test the efficacy of several compounds against cancer stem cells and experimental tumors, and correlate the responses to the original molecular make up of each tumor. Some of the agents being testing are already in clinical trials, others are in earlier development. We are then applying bioinformatics to study how the molecular networks in the tumor cells change in response to pharmacological interventions, towards the development of resistance to therapy. Our ultimate goals are first to identify measurable biomarkers that can predict responses to therapeutic interventions, for better selection of therapies. Second, we aim to design combination therapies that will take into account the dynamic and heterogeneous molecular characteristics of these tumors, much like the advances in the clinical management of AIDS, which have only been achieved with a multi-drug cocktail.
William and Karen Davidson Laboratory of Cell Signaling and Tumorigenesis (Chaya Brodie, Ph.D.)
Research in this laboratory focuses on understanding the signaling pathways associated with the oncogenic potential of glioma stem cells and their infiltrative nature. Nationally innovative research on glioma stem cells is being performed that includes studies of stemness, mesenchymal transformation, and therapy resistance of glioma stem cells. New approaches are being developed for the selective targeting of glioma stem cells using nanoparticles and mesenchymal stem cells through their precise delivery of miRNAs via their enclosed endosomes.
Laboratory of Translational Research (Steve Kalkanis, M.D.)
With a primary focus on development of personalized medicine protocols, research includes viral therapy for the most resistant tumors as well as investigations of the use “smart” stem cells as delivery vehicles for other targeted, cell-based, anti-tumor therapies. Potential applications of Raman spectroscopy are being investigated in collaboration with Wayne State University to determine whether scattered light waves can be employed to identify the presence of a single cancer cell amidst multiple normal cells, with the potential to allow a more complete surgical resection. Dr. Kalkanis is also a Co-Director of the Hermelin Brain Tumor Center and has numerous research subcontracts with collaborating universities.
Traumatic brain injury research (Asim Mahmood, M.D. and Ye Xiong, Ph.D.)
Traumatic brain injury (also known as TBI) is a significant health concern worldwide. Every year, an estimated 1.7 million people in the United States sustain TBI, and more than 5 million people are coping with disabilities from TBI at an annual cost of more than $60 billion. In addition, TBI is a risk factor for Alzheimer's and Parkinson’s diseases. No effective pharmacological treatments are currently available for TBI. Developing effective therapeutic treatments for TBI is essential.
Dr. Mahmood’s lab (Cerebral Injury Protection Lab) has been focused on investigating TBI pathophysiology and exploring cell-based and pharmaceutical therapies using animal TBI models. Our ongoing proposal is a major advance in this direction where we are combining cell based therapy with tissue engineering using collagen implants to optimize the treatment of TBI. In addition, we are working on pleiotropic or combinatorial agents that act on multiple pathways to reduce brain damage and/or enhance endogenous neurorestoration for treatment of TBI. Our TBI research projects have been funded five times by NIH (4 R01s and 1 P01). Our ultimate goal is to develop new therapies to promote neural repair, and improve functional recovery and quality of life after TBI.
In 2011 Henry Ford Health System’s Neurosurgery Research Department became the Coordinating Center for The Michigan Spine Surgery Improvement Collaborative (MSSIC). MSSIC is a statewide quality improvement collaborative involving hospitals, orthopaedic surgeons and neurosurgeons who will seek to measure and improve the care and outcomes of patients who undergo spine surgery. This Collaborative is supported by Blue Cross Blue Shield of Michigan and will continue for years to come. This Collaborative will help make spine surgeries of the future in Michigan safer than the national average.
Resident research and journal club
Dr. Beverly Walters has recently become a consultant to the department. Dr. Walters’s a neurosurgeon and clinical epidemiologist who retired from a full time clinical practice in general neurosurgery, focusing on spine, brachial plexus, and peripheral nerve, to pursue her interest in applied evidence-based medicine. Her experience in clinical research involves the design and implementation of randomized controlled trials, case-control studies, meta-analyses, and outcome measure evaluation, and she has written extensively on study design and assessment of the quality of medical literature.
She has extensive experience in survey methodology and has developed a statistical technique for use in generating evidence for use in algorithms when randomized controlled trials cannot be done. For many years, Dr. Walters was the chairperson of the Practice Guidelines Committee of the American Association of Neurological Surgeons, a member of the Outcomes Committee of the AANS/CNS, and a member of the Committee for the Assessment of Quality of the AANS/CNS. Her guidelines activities have included the development of the Guidelines for the Management of Severe Head Injury, the Guidelines for Prehospital Management of Traumatic Brain Injury, Guidelines for the Surgical Management of Traumatic Brain Injury, Guidelines for Penetrating Brain Injury, Acute Spinal Cord Injury Guidelines, Guidelines for the Treatment of Low Grade Gliomas, Guidelines for the Management of the Neurobehavioral Consequences of Traumatic Brain Injury and the Lumbar Fusion Guidelines. Her work on the Spinal Cord Injury Guidelines was recognized by the United States Congress for its achievement. She was also honored by the Congress of Neurological Surgeons for her guideline work with their Exceptional and Distinguished Service Award. In her consultant role at Henry Ford’s Neurosurgery Department, among other responsibilities, Dr. Walters will be overseeing resident research activities and hosting bimonthly journal clubs.