Walter Low Lab

Stem Cell Institute PhotoWalter Low, PhD, is a Professor in the Department of Neurosurgery. He earned his doctorate in Bioengineering/Neurophysiology from the University of Michigan and was an NSF/NATO postdoctoral fellow in Neurophysiology at Cambridge University, England.

Dr. Low's research is focused on the translational development of therapies for treating neurological disorders. Stem cells and neural progenitor cells are used in transplantation studies to replace neurons in conditions such as neurodegenerative disorders. Gene therapy approaches are used to correct gene mutations and reprogram cells to restore neurological function. Deep brain stimulation is used to modulate and activate neural networks. Computational biological and multi “omic” approaches are used to identify dysfunctional neural networks and underlying molecular alterations. Immunotherapies are being developed for targeting and eradicating malignant brain tumors.

Low's investigation into using the Zika virus to help fight cancer was featured in this Kare11 news feature.

Learn about the lab's research areas below.

  • Stem Cells for Stroke
  • Neural Cell Transplantation
  • Gene Therapy
  • Brain Tumor Immunotherapies
  • Exogenic Organs/Cells
  • DBS/MRI Brain Imaging
  • Bioinformatics
  • Lab News
  • Our Team
  • Location & Resources
  • Stem Cells for Stroke

    Current standard of care for treating patients with ischemic stroke is the administration of tPA to break down clots within cerebral blood vessels. Unfortunately, only 5% of individuals with ischemic stroke reach hospitals within the 3-4 hours after their stroke to qualify for this treatment. We discovered a CD34-negative population of stem cells in human umbilical cord blood that can be administered 48 hours after ischemic injury and reduce infarct volume (a small localized area of dead tissue resulting from failure of blood supply) by approximately 50% and restore neurological function. We are currently conducting pre-clinical studies to obtain data to apply to the FDA for an Investigational New Drug to conduct a Phase I safety trial using these stem cells to treat stroke patients.

    • Xiao J, Nan ZH, Motooka Y, Low WC. Transplantation of a novel cell line population of umbilical cord blood stem cells ameliorates neurological deficits associated with ischemic brain injury. Stem Cells and Development 14:722-733 (2005).
    • Stone, LL, Grande A, Low WC. Neural repair and neuroprotection with stem cells in ischemic stroke. Basic Sciences 3:599-614 (2013).
    • Stone LLH, Xiao F, Rotshafer J, Juliano M, Sanberg CD, Sanberg PR, Kuzmin-Nichol N, Grande A, Cheeran MC, Low WC. Amelioration of ischemic brain injury in rats with human umbilical cord blood stem cells: Mechanisms of action. Cell Transplantation 25: 1473-1488 (2016).
    • Shiao, ML, Yuan C, Crane AT, Voth JP, Juliano M, Hocum-Stone LL, Nan Z, Zhang Y, Kuzman-Nichols N, Sanberg PR, Grande AW, Low WC. Immunomodulation with Human Umbilical Cord blood Stem Cells Ameliorates Ischemic Brain Injury – A Brain Transcriptome Profiling Analysis. Cell Transplantation 28:864-873 (2019).
  • Neural Cell Transplantation

    Neural progenitor cells and stem cells can be transplanted for repair of the nervous system. Our studies were the first to demonstrate that cholinergic precursors of the medial septal nucleus could innervate the hippocampal formation to replicate the intrinsic innervation pattern, and restore neurological function in terms of electrophysiological responses, and learning and memory test measures. In addition, we conducted studies that demonstrated dopaminergic ventral mesencephalic precursor cells can innervate the striatum and correct neurological deficits in a genetic mouse model of Parkinson disease. We have also shown that pluripotent stem cells can be used to treat other neurological disorders.

    • Low WC, Lewis PR, Bunch ST, Dunnett SB, Thomas SR, Iversen SD, Bjorklund A, Stenevi U. Function recovery following neural transplantation of embryonic septal nuclei in adult rats with septohippocampal lesions. Nature 300:260 262 (1982).
    • Triarhou, L.C., Low WC, and B. Ghetti, Transplantation of ventral mesencephalic analgen to a genetic model of nigrostriatal dopamine deficiency, Proceedings of the National Academy of Science, 83:8789-8793 (1986).
    • Jiang, YH, BN Jahagirdar, RL Reinhardt, RE Schwartz, CD Keene, X. Ortiz-Gonzalez, M Reyes, T Lenvik, Lund, M Blackstad, JB Du, S Aldrich, A Lisberg, WC Low, DA Largaespada, CM Verfaillie, Pluripotent nature of adult marrow derived mesenchymal stem cells. Nature 418:41-49 (2002).
    • Terzic D, Maxon JR, Krevitt L, DiBartolomeo, Goyal T, Dutton JR, Low WC, Parr AM. Directed differentiation of oligodendrocyte progenitor cells from mouse induced pluripotent stem cells. Cell Transplantation 25:411-424 (2016).
    • Walsh P, Troung V, Saldia Montivero M, Nayak S, Low WC, Parr AM, Dutton J, Accelerated differentiation of human pluripotent stem cells into neural lineages via an early intermediate ectoderm population, Stem Cells (in press, 2020).
  • Gene Therapy

    The laboratory is also involved in developing gene engineering approaches to correct neurological disorders based on gene mutations or delivery therapeutic genes. Our group was the first to show the benefit of gene therapy in animal models of ataxia and Hurler’s syndrome with the latter demonstrating restoration of neurological function. These gene therapy studies are being extended to treat other neurological disorders.

    • Kaemmerer WF, Reddy RG, Warlick CA, Hartung SD, Zolotukhin S., McIvor RS, Low WC. In vivo transduction of cerebellar Purkinje Cells using adeno-associated virus vectors. Journal of Molecular Therapy 2:446-457 (2000).
    • Belur LR, Kaemmerer WF, McIvor RS, and Low WC. Adeno associate virus type 2 vectors: Transduction and long term expression in cerebellar Purkinje cells is mediated by fibroblast growth factor receptor 1. Archives of Virology 153:2107-2110 (2008).
    • Wolf DA, Banerjee S, Hackett PB, Whitley CB, McIvor RS, Low WC. Gene therapy for nervous system manifestations of mucopolysaccharidoses. Expert Opinion on Drug Delivery 10(2):e0116788.doi. (2015).
    • Laoharawee K, Podetz-Pedersen K, Nguyen T, Fairbanks C, Low WC, Kozarsky K, McIvor RS.  
    • Prevention of neurocognitive deficiency in mucopolysaccharidosis type II mice by CNS-directed AAV9-  mediated sulfatase gene transfer. Human Gene Therapy 28:626-638 (2017).
  • Brain Tumor Immunotherapies

    The lab team was one of the first to demonstrate the efficacy of immunotherapy for treating brain tumors. These studies were initially performed in rodents with intracranial gliomas that were vaccinated with tumor lysate and GM-CSF to recruit dendritic cells for processing of tumor antigen and stimulation of T cells for clonal expansion for recognition and selective killing of tumor cells. Recently, we have begun studying the use of the viruses for activation of the immune response against brain tumors.

    • Olin M, Low WC, McKenna DH, Haines SJ, Tambra D, Nacene D, Gustafson MP, Dietz AB, Clark HB, Chen W, Blazar B, Ohlfest JR, Moertel C. Vaccination with dendritic cells loaded with allogeneic brain tumor stem cells for recurrent and progressive malignant brain tumors induces a CD4+IL17+ response. Journal for Immunotherapy of Cancer 18;2:4 (2014).
    • Gardeck AM, Sheehan J, Low WC. Immune and viral therapies for brain cancer. Expert Opinion on Biological Therapies 17(4):457-474 (2017).
    • Pearce CM, Chrostek MR, Fellows EG, Toman NG, Tran S, Crane AT, Low WC. Immunotherapy and checkpoint inhibitors for gliomas. Neuroimmunology and Neuroinflammation 5:47, doi 1.20517/2347-8659.2018.46 (2018).
    • Crane AT, Chrostek MR, Krishna VD, Shiao M, Toman NG, Pearce C, Tran SK, Sipe CJ, Buo W, Voth JP, Vaid S, Xie H, Lu WC, Swanson W, Grande AW, Schleiss MR, Bierle CJ, Cheeran MCJ, Low WC, Zika virus-based immunotherapy enhances long-term survival of rodents with brain tumors through upregulation of memory T-cells, PLOS ONE (in press, 2020)
  • Exogenic Organs/Cells

    A new avenue of research in the Low Laboratory is the generation of organs and cells for regenerative medicine by the targeted knockout of organ/cell specific genes in embryos and transfer of wild-type stem cells to occupy the ablated niche for the development of the desired organs/cells. Potentially, this approach for the generation of human-animal chimeras could provide an abundant source of organs/cells for transplantation.

    • Crane AT, Aravalli RN, Asakura A, Grande AW, Krishnan VD, Carlson DF,Cheeran MCJ, Danczyk G, Durron JR, Hackett PB, Hu WS, Li L, Lu WC, Miller ZD, O’Brien T, Panoskaltsis-Mortari A, Parr AM, Pearce C, Ruiz M, Shiao M, Sipe C, Toman NG, Voth J, Xie H, Steer, CJ, and Low WC,  Interspecies organogenesis for human transplantation, Cell Transplantation. doi: 10.1177/0963689719845351. (2019).
    • Crane AT, Voth JP, Shen FX, and Low WC, Human-animal neurological chimeras: humanized animals or human cells in an animal, Stem Cells. doi: 10.1002/stem.2971. (2019)
    • Crane AT, Shen FX, Brown JL, Carmack W, Ruiz-Estevez M, Voth JP, Sawai T, Hatta T, Fujita M, and Low WC, The American public is ready to accept human-animal chimera research, Stem Cell Reports (in press, 2020).
  • DBS/MRI Brain Imaging

    Modulating brain activity with deep brain stimulation (DBS) has emerged as an effective form of therapy for numerous neurological disorders. Current investigations in this area of research in the lab include miniaturization of the electrode size to nanoscale dimensions, orientation-selective activation by directing electromagnetic fields, and employing MRI brain imaging technologies to monitor effects of neuromodulation.

    • Michaeli S, Burns TC, Kudishevich E, Harel N, Hanson T, Sorce DJ, Garwood M, Low WC. Detection of neuronal loss using T1(rho) MRI assessment of (1)H(2)O spin dynamics in the aphakia mouse. J Neurosci Methods. 177(1):160-7 (2009)
    • Satzer D, DiBartolomeo C, Ritchie MM, Storino C, Liimatainen T, Hakkarainen H, Idiyatullin D, Mangia S, Michaeli S, Parr AM, Low WC. Assessment of dysmyelination with RAFFn MRI: application to murine MPS I. PLoS One.  10(2):e0116788  (2015)
    • Lehto LJ, Slopsema JP, Johnson MD, Shatillo A, Teplitzky BA, Utecht L, Adriany G, Mangia S, Sierra A, Low WC, Gröhn O, Michaeli S. Orientation selective deep brain stimulation. J Neural Eng.14(1):016016. doi: 0.1088/1741-2552/aa5238 (2017)
    • Lehto LJ, Filip P, Laakso H, Sierra A, Slopsema JP, Johnson MD, Eberly LE, Low WC, Gröhn O, Tanila H, Mangia S, Michaeli S. Tuning neuromodulation effects by orientation selective deep brain stimulation in the rat medial frontal cortex. Frontiers in Neurosci.12:899 (2018)
    • Lehto LJ, Canna A, Wu L, Sierra A, Pearce C, Shaio M, Filip P, Johnson MD, Low WC, Gröhn O, Tanila H, Mangia S, Michaeli S., Orientation selective deep brain stimulation of the subthalamic nucleus in rats. NeuroImage. 213:116750. (2020).
  • Bioinformatics

    Another area of research focus is on developing diagnostic biomarkers of disease, disease progression, and response to therapies. Current investigations involve computational biology approaches applied to analysis of transcriptome, proteome, and metabolome data sets.

    • Nikas J and Low WC, ROC-Supervised Principal Component Analysis in Connection with the Diagnosis of Diseases, American Journal of Translational Research 3:180-196 (2011)
    • Nikas J, and Low WC, Application of clustering analyses to the diagnosis of Huntington disease in mice and other diseases with well-defined group boundaries,  Computer Methods and Programs in Biomedicine, 104:e133-147 (2011)
    • Nikas JB, Boylan KL, Skubitz AP, and Low WC, Mathematical prognostic models for treatment response and survival in epithelial ovarian cancer, Cancer Informatics 10:233-247 (2011)
    • Nikas JB and Low WC, Linear discriminant functions in connection with the microRNA diagnosis of colon cancer. Cancer Informatics 11:1-14 (2012).
    • Satzer, D, Miller, C, Maxon J, Dibartolomeo C, Dutton JR, Low WC, and Parr AM, T cell deficiency in spinal cord injury – altered locomotor recovery and whole-genome transcriptional analysis, BMC Neuroscience 16:74 Epub ahead of print (2015)
    • Shiao, ML, Yuan C, Crane AT, Voth JP, Juliano M, Hocum-Stone LL, Nan Z, Zhang Y, Kuzman-Nichols N, Sanberg PR, Grande AW, Low WC. Immunomodulation with Human Umbilical Cord blood Stem Cells Ameliorates Ischemic Brain Injury – A Brain Transcriptome Profiling Analysis. Cell Transplantation 28:864-873 (2019).
  • Lab News

    The Low Lab is featured in this Stem Cell Reports article: The American Public Is Ready to Accept Human-Animal Chimera Research and in this press release about the same topic: Survey finds American support for human-animal chimera research.

     

  • Our Team

    CURRENT LAB MEMBERS

    Postdoctoral Research Associates
    Andrew Crane
    Maple Shiao
    Aleta Steevens
    Susanne Var

    Graduate Students
    Isaac Clark
    Nicole Emmitt
    Swathi Radha
    Alex Roman
    Anala Shetty

    Medical Students
    Emily Fellows
    Tony Larson

    Undergraduate Students
    Chris Carchi
    Samantha Johnson
    Kashif Qureshi

    Laboratory Manager
    Nick Toman

    See present and past lab members.

  • Location & Resources

    Location

    Dr. Low’s laboratory is located on the 4th floor of the Lions Research Building on the corner of Sixth Street SE and Oak Street. The Translational Research Facility was recently added to the Lions Research Building.

    Resources

    Required training for new lab members