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Neural Stem Cell Working Group

This Working Group brings expertise in developmental, systems and cell neurobiology to their efforts to use stem cells to create potential therapies for spinal cord injury, neurodegeneration, traumatic brain injury, epilepsy and psychiatric disorders, including addiction and schizophrenia. The group combines diverse backgrounds of engineers, biochemists, cell biologists, neuroscientists, neurologists and psychiatrists to find the best solution for complex nervous system disorders. Projects in the group start from whole animal approaches of using advanced imaging techniques to guide and incorporate transplanted stem cell derived neurons to dissecting molecular pathways of cellular maturation to designing better artificial niche environments for commercial production of neural stem cells.

Group Leaders:

  • Candace Kerr, M.S., Ph.D.  

     Dr. Kerr’s team has shown that oligodendrocyte progenitors derived from induced pluripotent stem cell and embryonic stem cells possess significant regenerative ability when transferred into damaged rodent spinal cords and in rodent models of multiple sclerosis (with Dr. Jeff Bulte from Johns Hopkins University). These direct beneficial effects are mediated through early intervention and hypothermic treatment that increases survival of transplanted cells and reduces secondary effects of inflammation. In collaboration with Dr. Angelo All (Johns Hopkins University), Dr. Kerr’s group has demonstrated the ability of these progenitor cells to enhance remyelination of the injured spinal cord and to differentiate into mature oligodendrocytes.

    All AH, Bazley FA, Gupta S, Pashai N, Hu C, Pourmorteza A and Kerr CL. Human embryonic stem cell-derived oligodendrocyte progenitors aid in functional recovery of sensory pathways following contusive spinal cord injury", PLoS One. 2012;7(10):e47645. doi: 10.1371/journal.pone.0047645. Epub 2012 Oct 16. 

  • Marta Lipinski, Ph.D.  

    Dr. Lipinski studies autophagy, a cellular protein degradation pathway important for protection of organisms from a variety of diseases, including neurodegeneration, cancer and aging. Her lab concentrates on the function of autophagy in prevention of acute (brain trauma) and chronic (Parkinson’s disease) neuronal cell damage. Her long-term goal is to manipulate autophagy as a treatment against brain trauma and neurodegeneration.

    Lipinski MM, Hoffman G, Ng A, Zhou W, Py BF, Hsu E, Liu X, Eisenberg J, Liu J, Blenis J, Xavier RJ, Yuan J. A genome-wide siRNA screen reveals multiple mTORC1 independent signaling pathways regulating autophagy under normal nutritional conditions. Dev Cell. 2010 Jun 15;18(6):1041-52. doi: 10.1016/j.devcel.2010.05.005. 

Highlighted Group Members:

  • Laure Aurelian, Ph.D.   

    The Aurelian lab is using mesenchymal stem cells modified through the insertion of neuroprotective genes in order to overcome therapeutic limitations resulting from microenvironment toxicities caused by neuron-glial cell interactions and to better define the death programs to be targeted.

  • Cynthia  Bearer, M.D., Ph.D.  

    The developing central nervous system is vulnerable to a variety of toxicants including ethanol, solvents, bilirubin and volatile anesthetics. The Bearer laboratory is focused on understanding influences on lipid raft based neurite outgrowth as both the mechanism and a potential therapeutic target for these chemicals. We are using neural stem cells to model neuronal plasticity and serve as an in vitro model of neurodevelopment.

  •  Steven Bernstein, M.D., Ph.D. 

    Diseases of the optic nerve, such as glaucoma, optic neuritis and nonarteritic anterior ischemic optic neuropathy (NAION) are responsible for a large proportion of acquired blindness in the United States and developed world. Our laboratory is evaluating the role of progenitor cells in the development and repair of the damaged optic nerve and retina. We utilize both in vivo and cell culture methodologies to improve early recovery, and to understand the mechanisms that will enhance current treatment strategies.

  • Christopher Bever, Ph.D.  

    The Bever Group (Drs. Chris Bever, Tapas Makar and David Trisler) studies the use of hematogenous stem cells in cell replacement therapy and gene delivery. Ten years ago the group developed a method for growing CD34+ stem cells from bone marrow and showed that when transplanted into experimental animals they could differentiate into a wide range of neuronal and other cell types. More recently in blastocyst transplantation studies we have shown that the cells are capable of differentiating into all cell lineages. In addition we have engineered stem cells to deliver interferon beta, brain derived neurotrophic factor and ciliary neurtrophic factor and have used those cells in animal models of multiple sclerosis, spinal cord injury and brain trauma.

  • Paul Fishman, M.D., Ph.D.  

  • Gary Fiskum, Ph.D.  

  • Rao Gullapalli, Ph.D., MBA  

  • L. Elliot Hong, M.D.  

    Dr. Hong is a psychiatrist who is collaborating with Drs Ricardo Feldman and Patricio O’Donnell to develop human iPSC from patients with severe nicotine addiction. Their goal is to identify clinically obtained phenotypes from patients, and to find cellular phenotypes from the iPSC derived neurons that correspond to these clinical phenotypes. The long-term goal of this collaboration is to develop sets of well-characterized lines from patients with psychiatric conditions and achieve cellular phenotypes that have clinical predictive values.

  • Tibor Kristian, Ph.D.  

    The goal of the Kristian lab research is to use genetically modified stem cells for treatment of stroke and other neurologic disorders. The extremely low rate of survival of the engrafted cells into the hostile brain environment created following injury remains one of the major factors that limit the efficiency of these transplantation strategies. We use RNA interference-base strategy to increase survival of neuronal progenitors transplanted in the post—ischemic brain.

  • Jennie Leach, Ph.D.  

    Research within the Leach laboratory at UMBC focuses on designing biomaterials and sensors for tissue engineering applications. We design, synthesize and characterize biomaterials created from naturally derived and synthetic biopolymers. Particular interest centers on delineating quantitative relationships between properties of three-dimensional cell scaffolds and the elicited signaling mechanisms of cells grown within the materials. Current work focuses on 1) scaffolds to support neural regeneration and transplant of neural stem cells; 2) in vitro models of neurophysiology; and 3) novel sensor platforms for mapping hypoxia in areas of high metabolic activity, such as tissues undergoing regeneration or tumor morphogenesis. We have collaborated with Dr. Elizabeth Powell on the projects related to neural and neural stem cell applications.

    Ribeiro A, Vargo S, Powell EM, Leach JB. Substrate three-dimensionality induces elemental morphological transformation of sensory neurons on a physiologic timescale. Tissue Eng Part A. 18(1-2):93-102.(2012) doi: 10.1089/ten.tea.2011.0221. Epub 2011 Sep 12. 

  • Margaret McCarthy, Ph.D.  

    The McCarthy lab studies the effects of early life programming by steroid hormones on the developing brain. Neural progenitor cells in the hippocampus and amygdala are impacted by steroid hormones but in different ways. A major research goal is to understand how these progenitor cells are differentiated into neurons versus glia and the functional consequences of this process.

  • Rosengela Mezghanni, Ph.D.  

  • Sandra Mooney, Ph.D.  

    The Mooney lab investigates the effects of drugs, including alcohol and valproic acid, on stem and progenitor cell development. In vivo models are used to evaluate behavioral outcomes, as well as alterations in anatomy, metabolism, and protein and gene expression in the brain. In vitro models are used to understand effects on cell cycle parameters and the involvement of and requirement for growth factors.

  • Kiran Panickar, Ph.D.  

  • Elizabeth Powell, Ph.D.  

    The Powell laboratory is focused on the cellular and molecular mechanisms that lead to altered early brain development in epilepsy and autism. The laboratory has collaborated with Dr. Gullapalli in imaging abnormal brain morphology in mouse mutants of genes associated with autism. The laboratory also has a long standing collaboration with Dr. Leach (UMBC) in designing better substrates for tissue engineering and methods to control neural stem cell fate and morphology in preparation for use in regenerative therapies.

    Ribeiro A, Vargo S, Powell EM, Leach JB. Substrate three-dimensionality induces elemental morphological transformation of sensory neurons on a physiologic timescale. Tissue Eng Part A. 18(1-2):93-102.(2012) doi: 10.1089/ten.tea.2011.0221. Epub 2011 Sep 12. 

  • Adam Puche, Ph.D.  

    The Puche group has interests in the continual formation and migration of stem cells in the adult brain. These cells are born in a central region of the brain and migrate long distances to their cortical targets in the olfactory system. However, the molecular mechanisms regulating the movement of stem cells in the adult brain are unclear. Understanding how to control the movement of endogenous and transplanted stem cells are critical information if transplanted stem cells are to be used as effective neuronal replacement therapies. Using a combination of neuroanatomical, surgical, tissue culture, and molecular approaches we are investigating the migration and differentiation of stem cells in the adult brain.

  • Jean-Pierre Raufman, Ph.D.  

  • Sheelu Varghese, Ph.D.  

    Our team is studying neural cell development from cancer stem cells predominantly differentiation of mesenchymal stem cells. Embryonic stem cell markers, neural and endothelial cell markers were validated during tumor formation as we believe that the coordinated dedifferentiation and transdifferentation of both endothelial and neural cells promote tumor growth in abdominal cancers. Such studies could lead into the identification of new mechanisms of drug resistance, tumor relapse and metastasis.

  • Paul Yarowsky, Ph.D.  

    The Yarowsky group (Paul Yarowsky, Adam Puche, and Paul Fishman) are developing innovative medical protocols to treat traumatic brain injury (TBI) using site directed magnetic targeting of neural stem cells (NSCs) labeled with benign magnetic nanoparticles. We are labeling NSCs with magnetic nanoparticles (NP) and then controlling the magnetic NSCs’ migration and retention using magnetic fields. The inability to control the phenotype, viability, retention and migration of implanted stem cells in living animals is a major limitation in stem cell therapy and a significant concern for using stem cells for TBI therapy. Our research to overcome these challenges is (i) a magnetic iron oxide nanoparticle that efficiently labels stem cells, (ii) a method for tracking and quantifying both the location and therapeutic action of the labeled stem cells within the brain by MRI, (iii) a device to magnetically direct and retain stem cells at the site of injury and (iv) a method for long-term storage and rapid retrieval of the magnetically labeled stem cells. These methods will give a more efficient tissue rescue and regeneration of damaged brain tissue than is available using current technology.