Walter Low , PhD

Professor, Department of Neurosurgery

Education

Biography

Dr. Walter Low is a Professor in the Department of Neurosurgery and serves as the Associate Head for Research. He earned his PhD in Bioengineering from the University of Michigan, and was a National Science Foundation/NATO Fellow in Neurophysiology/Neuroscience at the University of Cambridge in England. He is currently Director of the Research Laboratories in the Department of Neurosurgery.

Dr. Low was formerly on the faculty at Indiana University School of Medicine where he was the Director of the Graduate Program in Physiology and Biophysics. He has served as a member of numerous grant review study sections for the National Institutes of Health, the National Science Foundation, and the Veterans Administration Medical Centers.

The h-index for the scientific impact of Dr. Low's research publications is ranked above the 95th percentile among faculty in neurosurgery departments in the United States.

Research

Research Summary

Dr. Low's research is focused on translating neuroscience developments from the laboratory to the clinic. He has been involved in a number of technologies that include neural progenitor/stem cell therapies, gene therapies, neuroprotective therapies, and medical devices for treating a variety of neurological conditions. Neural disorders of interest include ischemic and hemorrhagic stroke, Parkinson's disease, brain tumors, Alzheimer's disease, lysosomal storage disorders of the brain, Huntington's disease, spinal cord injury, and traumatic brain injury.

Dr. Low's group was the first to: Demonstrate that the transplantation of cholinergic neurons into the hippocampal formation could restore learning and memory function in a rat model of Alzheimer's disease Demonstrate the efficacy of immunotherapy for eradicating intracranial tumors in rodents Receive FDA approval for clinical trials in the United States to study the efficacy of deep brain stimulation for the treatment of Parkinson's disease. Read more.

Brain and tumor immunology and development of cancer vaccines

Dr. Low's laboratory is focused on the study of brain tumors. Primary tumors that originate in the brain represent some of the most malignant types of cancers. Patients diagnosed with grade IV glioblastoma multiforme have a mean survival time of 11 months after diagnosis. Our studies of brain tumors have emphasized the development of immunotherapeutic approaches for the treatment of these tumors. Cancer vaccines consisting of cytokines and tumor antigens are used to stimulate cells of the immune system to recognize and destroy tumors within the brain.

Publications

Selected Publications

2022. (Strell, P, Shetty A, Steer CJ and Low WC, Interspecies chimeric barriers for generating exogenic organs and cells for transplantation, Cell Transp 2022, Jan-Dec;31:9636897221110525. doi: 10.1177/09636897221110525). Interspecies chimeric barriers for generating exogenic organs and cells for transplantation.

2022. (Cell Reprogramming for Regeneration and Repair of the Nervous System. Clark IH, Roman A, Fellows E, Radha S, Var SR, Roushdy Z, Borer SM, Johnson S, Chen O, Borgida JS, Steevens A, Shetty A, Strell P, Low WC, Grande AW.Biomedicines. 2022 Oct 17;10(10):2598. doi: 10.3390/biomedicines10102598. ). Cell Reprogramming for Regeneration and Repair of the Nervous System.

2022. (Wu L, Canna A, Narvaez O, Ma J, Sang S, Lehto LJ, Sierra A, Tanila H, Zhang Y, Gröhn O, Low WC, Filip P, Mangia S, Michaeli S. Orientation selective DBS of entorhinal cortex and medial septal nucleus modulates activity of rat brain areas involved in memory and cognition. Sci Rep. 2022 May 20;12(1):8565. doi: 10.1038/s41598-022-12383-2.). Orientation selective DBS of entorhinal cortex and medial septal nucleus modulates activity of rat brain areas involved in memory and cognition.

2022. (Saha R, Faramarzi S, Bloom RP, Benally OJ, Wu K, di Girolamo A, Tonini D, Keirstead SA, Low WC, Netoff TI, Wang JP. Strength-frequency curve for micromagnetic neurostimulation through excitatory postsynaptic potentials (EPSPs) on rat hippocampal neurons and numerical modeling of magnetic microcoil (μcoil). J Neural Eng. 2022 Feb 4;19(1). doi: 10.1088/1741-2552/ac4baf.). Strength-frequency curve for micromagnetic neurostimulation through excitatory postsynaptic potentials (EPSPs) on rat hippocampal neurons and numerical modeling of magnetic microcoil (μcoil).

2021. (Var SR, Shetty AV, Grande AW, Low WC, Cheeran MC. Microglia and Macrophages in Neuroprotection, Neurogenesis, and Emerging Therapies for Stroke. Cells. 2021 Dec 16;10(12):3555. doi: 10.3390/cells10123555.). Microglia and Macrophages in Neuroprotection, Neurogenesis, and Emerging Therapies for Stroke.

2021. (Harris MA, Kuang H, Schneiderman Z, Shiao ML, Crane AT, Chrostek MR, Tăbăran AF, Pengo T, Liaw K, Xu B, Lin L, Chen CC, O'Sullivan MG, Kannan RM, Low WC, Kokkoli E. ssDNA nanotubes for selective targeting of glioblastoma and delivery of doxorubicin for enhanced survival. Sci Adv. 2021 Dec 3;7(49):eabl5872. doi: 10.1126/sciadv.abl5872.). SSDNA nanotubes for selective targeting of glioblastoma and delivery of doxorubicin for enhanced survival.

(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, 15:804-810 (2020).). The American public is ready to accept human-animal chimera research.

(Do TH, Miller C, Low WC, Haines SJ, The Radicchi Index (hf) for Comparing Academic Productivity of Medical Specialties, Neurosurgery, doi: 10.1093/neuros/nyz207.(in press, 2019).). The Radicchi Index (hf) for Comparing Academic Productivity of Medical Specialties.

(Toman, N, Grande AW, and Low WC, Neural repair in stroke, Cell Transplantation doi: 10.1177/0963689719863784. (2019). ). Neural repair in stroke.

(Chrostek MR, Fellows EG, Guo WL, Swnson WJ, Crane AT, Cheeran MC, Low WC, and Grande, AW, Efficacy of cell-based therapies for traumatic brain injuries, Brain Sciences (in press, 2019).). Efficacy of cell-based therapies for traumatic brain injuries.

(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).). Interspecies organogenesis for human transplantation.

(Chrostek MR, Fellows EG, Crane AT, Grande AW, and Low WC, Efficacy of Stem Cell-Based Therapies for Stroke, Brain Research. doi: 10.1016/j.brainres.2019.146362. (2020).). Efficacy of Stem Cell-Based Therapies for Stroke.

(Ruiz-Estevez M, Crane AT, Rodriguez-Villamil P, Ongaratto FL, Steevens A, Hill C, Goldsmith T, Webster D, Sherry L, Denman N, Lim S, Low WC, Carlson DF, Dutton JR, Steer CJ, Gafni O, Liver development in restored by blastocyst complementation of HHEX knockout in mice and pigs, Stem Cell Research and Therapy, doi:10.1186/s13287-02348-z (2021).). Liver development in restored by blastocyst complementation of HHEX knockout in mice and pigs.

(Li Y, Yi B, Rong G, Wang, Zhang, Chrostek M, Low WC, Zhu X, and Chen W, Machine Learning-Enabled High-Resolution Dynamic Deuterium MR Spectroscopic Imaging, IEEE Transactions in Medical Imaging, 40(12):3879-3890 (2021).). Machine Learning-Enabled High-Resolution Dynamic Deuterium MR Spectroscopic Imaging, IEEE Transactions in Medical Imaging.

(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 38:1400-1408 (2020).). Accelerated differentiation of human pluripotent stem cells into neural lineages via an early intermediate ectoderm population.

(Lehto LJ, Canna A, Wu L, Sierra A, Pearce C, Shiao M, Johnson MD, Low WC, Grohn O, Tanila H, Mangia S, and Michaeli S, Orientation selective deep brain stimulation of the subthalamic nucleus in rats, Neuroimaging, 213:116750, doi:10.1016/j.neuroimage.2020.116750. (2020).). Orientation selective deep brain stimulation of the subthalamic nucleus in rats.

(Belur, LR, Romera M Lee J, Poetz-Pedersen KM, Nan Z, Riedl MS, Vulshanova L, Kitto KF, Fairbanks, CA, Kozarsky KF, Orchard PJ, Frey WH 2nd, Low WC, and McIvor RS, Comparative effectiveness of intracerebroventricular, intrathecal, and intranasal routes of AAV9 vector administration for genetic therapy of neurologic disease in murine muscopolysaccharidosis Type I, Frontiers in Molecular Neuroscience, doi:10.3389/fnmol.2021618360. eCollection (2021). ). Comparative effectiveness of intracerebroventricular, intrathecal, and intranasal routes of AAV9 vector administration for genetic therapy of neurologic disease in murine muscopolysaccharidosis Type I.

(Sathe AG, Tuite P, Chen C, Ma YW, Chen W, Cloyd J, Low WC, Steer CJ, Lee BY, Zhu XH, and Coles LD, Pharmacokinetics, safety and tolerability of orally administered ursodeoxycholic acid in patients with Parkinson’s disease – A pilot study, Journal of Clinical Pharmacology, 11(3):145. doi: 10.3390/metabo11030145. (2020).). Pharmacokinetics, safety and tolerability of orally administered ursodeoxycholic acid in patients with Parkinson’s disease – A pilot study.

(Zhu XH, Lee BY, Tuite P, Coles L, Sathe AG, Cloyd J, Low WC, Steer CJ, Chen C, and Chen W, Quantitative assessment of occipital metabolic and energetic changes in Parkinson’s patients using in vivo 31P MRS-based metabolic imaging at 7T, Metabolites 11(3):145. doi: 10.3390/metabo11030145 (2021).). Quantitative assessment of occipital metabolic and energetic changes in Parkinson’s patients using in vivo 31P MRS-based metabolic imaging at 7T.

(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)). Human-animal neurological chimeras: humanized animals or human cells in an animal.

(Zhan L. Guo S, Kangas, J, Shao Q, Shiao M, Khosla K, Low WC, McAlpine M, and Bischof J. Conduction cooling and plasmonic heating dramatically increase droplet vitrificaiton volumes for cell cryopreservation, Advanced Sciences, 8: 2004605 (1-14), DOI: 10.1002/advs.202004605 (2021).). Conduction cooling and plasmonic heating dramatically increase droplet vitrificaiton volumes for cell cryopreservation.

(Shiao ML, Yuan C, Crane AT, Voth JP, Juliano M, Hocum-Stone LL, Nan Z, Zhang Y, Kuzman-Nichols N, Sanberg PR, Grande AW, and Low WC, Immunomodulation with human umbilical cord blood stem cells ameliorates ischemic brain injury – A brain transcriptome profiling analysis, Cell Transplantation. doi: 10.1177/0963689719836763. (2019).). Immunomodulation with human umbilical cord blood stem cells ameliorates ischemic brain injury – A brain transcriptome profiling analysis.

(Crane AT, Shen FX, Low WC, Continuing the dialog on human-animal chimerism, Stem Cell Reports, 16:227 (2021).). Continuing the dialog on human-animal chimerism.

(Lehto LJ, Filip P, Laakso H, Sierra A, Slopsema J, Johnson MD, Eberly LE, Utecht L, Low WC, Grohn O, Tanila H, Mangia S, and Michaeli S, Tuning neuromodulation effects by orientation selective deep brain stimulation in the rat medial frontal cortex. Frontiers in Neuroscience, doi: 10.3389/fnins.00899. (2019).). Tuning neuromodulation effects by orientation selective deep brain stimulation in the rat medial frontal cortex.

(Steevens AR, Griesbach MW, You Y, Dutton JR, Low WC, and Santi PA, Generation of inner ear sensory neurons using blastocyst complementation in a Neurog1-deficient mouse. Stem Cells & Developmental Biology, 12(1):122. doi: 10.1186/s13287-021-02184-1. (2021).). Generation of inner ear sensory neurons using blastocyst complementation in a Neurog1-deficient mouse.

(Steevens AR, Glatzer JC, Kellogg CC, Low WC, Santi P, and Kiernam AE, SOX2 is required for inner ear growth and nonsensory formation prior to sensory development, Development. doi: 10.1242/dev.170522. (2019). ). SOX2 is required for inner ear growth and nonsensory formation prior to sensory development.

(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 15(10):e0232858. doi: 10.1371 (2020).). Zika virus-based immunotherapy enhances long-term survival of rodents with brain tumors through up regulation of memory T-cells

Grants and Patents

Selected grants

Award: "Magnetic Nanodevice Arrays for the Treatment of Neurological Disorders"

Sponsoring Organization: State of Minnesota University of Minnesota–Mayo Clinic Biotechnology Program

Funded Amount: 913049

Award: “Brain Connectome as a Novel Biomarker for Krabbe Disease”

Sponsoring Organization: Legacy of Angels

Funded Amount: 105000

Award: “Zika Virus-Based Immunotherapy for Treating Malignant Brain Tumors: FDA Enabling Studies”

Sponsoring Organization: Randy Shaver Cancer Research and Community Fund

Funded Amount: 79176

Award: “Modeling and Reversing Alzheimer’s Pathology via Human Brain Organoids”

Sponsoring Organization: UMN AHC Faculty Research Development Program

Funded Amount: 200000

Award: “Enhancing Zika Virus-Based Therapies for Treating Malignant Brain Tumors”

Sponsoring Organization: Randy Shaver Cancer Research and Community Fund

Funded Amount: 50000

Award: “Acute and Long-Term Impact of SARS-CoV2 Infection and its Interaction with APOE on Cognitive Function and Neuropathology in Aging and Alzheimer’s Disease”.

Sponsoring Organization: National Institutes of Health

Funded Amount: 3687171

Award: “Cell Reprogramming for Traumatic Brain Injury”