Julien Rossignol's lab is part of the Field Neurosciences Institute laboratory for Restorative Neurology that he co-directs with Dr. Gary L. Dunbar.
Julien Rossignol, Ph.D.
College of Medicine
1280 S. East Campus Drive, CMED 2428
Mount Pleasant, MI 48859
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Huntington’s disease and stem cells therapy
Huntington’s disease (HD) is one of the most debilitating neurological disorders. HD is an autosomal dominant disorder characterized by uncontrolled ballistic movements and by extensive neuronal degeneration, especially of the medium spiny neurons (MSNs) in the striatum. Although it is known that the pathology of HD is the result of a trinucleotide CAG repeat mutation (The Huntington’s Disease Collaborative Research Group, 1993), the mechanisms responsible for the onset of neuronal degeneration and the characteristic motor and cognitive dysfunction have not been elucidated. The only FDA-approved treatment for HD is Tetrabenazine, a drug which depletes monoamine concentrations, but provides only palliative motor benefits and produces adverse side effects which limit its usefulness (Huntington Study Group, 2006). Thus, no current therapies exist that can reduce the constellation of cognitive, motor and psychiatric symptoms, or slow the unrelenting progression of this fatal disorder.
One of the most promising strategies for treating HD has emerged with the advent of cellular therapies. Transplantations of embryonic cells in HD have shown some success, but rejection of these cells and their limited engraftment into the host tissue have mitigated the efficacy of this approach. Although other cell replacement approaches are being developed, transplantation of mesenchymal adult stem cells (MSCs) has gained considerable attention because of their ability to produce and release anti-inflammatory cytokines and neurotrophic factors. Our strategy of transplanting genetically altered MSCs that overexpress a critical neurotrophin, brain derived neurotrophic factor (BDNF), has been targeted for clinical trials, funded by a $17 million grant from the California Institute of Regenerative Medicine to University of California, Davis. Although we believe this strategy is currently one of the most promising therapeutic approaches for slowing the relentless progression of HD, we believe that the efficacy of MSCs for treating HD can be further enhanced by co-transplanting them with induced-pluripotent stem cells (iPSCS), when either or both of these cell population are genetically altered to overexpress BDNF.
Nanoparticles and Huntington’s disease
Huntington’s disease (HD) is a devastating, fatal, autosomal dominant, neurodegenerative disorder, characterized by a relentless loss of cognitive and motor function which affects about 1 in 50,000 people, and which has, to date, remained refractory to any cure or treatment strategy. The use of stem cells and gene-editing techniques offer significant promise, but systemically delivering therapeutic biomolecules throughout the body, especially across the blood-brain barrier, remains a significant obstacle in developing an effective treatment. We are working on developing a novel way of delivering drugs or compound into the brain by studying the safety and biodistribution of a novel family of dendrimers to mesenchymal stem cells (MSCs) as a potential means of delivering therapeutic biomolecules.
Live nanoparticle detection in vivo after injection into the mouse brain.
Zika virus and stem cells
After the recent discovery that infection with Zika during pregnancy can lead to microcephaly in infants, there has been a huge response from the scientific community to determine the virus’ effect on the developing brain. We have been infecting human and mouse neural stem cells with the virus to understand how these cells respond to the virus. Our previous work with mouse neural stem cells has shown that the cells attempt to combat the virus by increasing the expression of genes important for the production of astrocytes, cells in the brain that are important for combating infection, supporting neurons, and regenerating the nervous system after an injury. Future studies include exploring how the virus effects differentiating neural stem cells, determining the inflammatory response to infection, and whether the virus effects the neuronal firing properties of mature neurons.
We are currently looking for student volunteers who would like to gain valuable laboratory experience and those who would like to complete an honors capstone project and are interested in our ongoing neuroscience research. Please contact Dr. Julien Rossignol for more information at firstname.lastname@example.org