Bio

Professional Education


  • Neurosurgery Residency, Stanford University
  • Doctor of Medicine, University of Minnesota Twin Cities (2009)
  • Doctor of Philosophy, University of Minnesota Twin Cities (2007)
  • Bachelor of Science, Columbia Union College (2001)

Stanford Advisors


Research & Scholarship

Current Research and Scholarly Interests


My research interests include understanding the behavior of endogenous and transplanted stem cells in the healthy and diseased brain, with a goal of developing translational neuroregenerative therapies. My current work in the lab of Theo Palmer includes efforts to reactivate neurogenesis after brain irradiation for treatment of brain tumors. Specifically, our current projects include profiling the cellular and transcriptional changes occurring after brain irradiation, testing candidate strategies to overcome these changes, and developing strategies to reactivate or replace dysfunctional neural stem cells in the irradiated neurogenic niche.

Lab Affiliations


Publications

Journal Articles


  • MAPC culture conditions support the derivation of cells with nascent hypoblast features from bone marrow and blastocysts JOURNAL OF MOLECULAR CELL BIOLOGY Lo Nigro, A., Geraerts, M., Notelaers, T., Roobrouck, V. D., Muijtjens, M., Eggermont, K., Subramanian, K., Ulloa-Montoya, F., Park, Y., Owens, J., Burns, T. C., Low, W., Sharma, S., Sohni, A., Crabbe, A., Pauwelyn, K., Roelandt, P., Agirre, X., Prosper, F., O'Brien, T. D., Zwijsen, A., Hu, W., Binas, B., Verfaillie, C. M. 2012; 4 (6): 423-426

    View details for DOI 10.1093/jmcb/mjs046

    View details for Web of Science ID 000312890900009

    View details for PubMedID 22878264

  • Sex Differences in Clinical Presentation and Treatment Outcomes in Moyamoya Disease NEUROSURGERY Khan, N., Achrol, A. S., Guzman, R., Burns, T. C., Dodd, R., Bell-Stephens, T., Steinberg, G. K. 2012; 71 (3): 587-593

    Abstract

    Moyamoya (MM) disease is an idiopathic steno-occlusive angiopathy occurring more frequently in females.To evaluate sex differences in preoperative symptoms and treatment outcomes after revascularization surgery.We analyzed 430 MM disease patients undergoing 717 revascularization procedures spanning 19 years (1991-2010) and compared gender differences in preoperative symptoms and long-term outcomes after surgical revascularization.A total of 307 female and 123 male patients (ratio, 2.5:1) with a mean age of 31.0 ± 16.7 years and adults-to-children ratio of 2.5:1 underwent 717 revascularization procedures. Female patients were more likely to experience preoperative transient ischemic attacks (odds ratio: 2.1, P = .001) and less likely to receive a diagnosis of unilateral MM disease (odds ratio: 0.6, P = .04). No association was observed between sex and risk of preoperative ischemic or hemorrhagic stroke. There was no difference in neurological outcome because both male and female patients experienced significant improvement in the modified Rankin Scale score after surgery (P < .0001). On Kaplan-Meier survival analysis, 5-year cumulative risk of adverse postoperative events despite successful revascularization was 11.4% in female vs 5.3% in male patients (P = .05). In multivariate Cox proportional hazards analysis, female sex trended toward an association with adverse postoperative events (hazard ratio: 1.9, P = .14).Female patients are more susceptible to the development of preoperative transient ischemic attack and may be at higher risk of adverse postoperative events despite successful revascularization. There is, however, no sex difference in neurological outcome because patients of both sexes experience significant improvement in neurological status with low risk of the development of future ischemic events after surgical revascularization.

    View details for DOI 10.1227/NEU.0b013e3182600b3c

    View details for Web of Science ID 000308074400016

    View details for PubMedID 22718024

  • Intracranial hypotension producing reversible coma: a systematic review, including three new cases A review JOURNAL OF NEUROSURGERY Loya, J. J., Mindea, S. A., Yu, H., Venkatasubramanian, C., Chang, S. D., Burns, T. C. 2012; 117 (3): 615-628

    Abstract

    Intracranial hypotension is a disorder of CSF hypovolemia due to iatrogenic or spontaneous spinal CSF leakage. Rarely, positional headaches may progress to coma, with frequent misdiagnosis. The authors review reported cases of verified intracranial hypotension-associated coma, including 3 previously unpublished cases, totaling 29. Most patients presented with headache prior to neurological deterioration, with positional symptoms elicited in almost half. Eight patients had recently undergone a spinal procedure such as lumbar drainage. Diagnostic workup almost always began with a head CT scan. Subdural collections were present in 86%; however, intracranial hypotension was frequently unrecognized as the underlying cause. Twelve patients underwent one or more procedures to evacuate the collections, sometimes with transiently improved mental status. However, no patient experienced lasting neurological improvement after subdural fluid evacuation alone, and some deteriorated further. Intracranial hypotension was diagnosed in most patients via MRI studies, which were often obtained due to failure to improve after subdural hematoma (SDH) evacuation. Once the diagnosis of intracranial hypotension was made, placement of epidural blood patches was curative in 85% of patients. Twenty-seven patients (93%) experienced favorable outcomes after diagnosis and treatment; 1 patient died, and 1 patient had a morbid outcome secondary to duret hemorrhages. The literature review revealed that numerous additional patients with clinical histories consistent with intracranial hypotension but no radiological confirmation developed SDH following a spinal procedure. Several such patients experienced poor outcomes, and there were multiple deaths. To facilitate recognition of this treatable but potentially life-threatening condition, the authors propose criteria that should prompt intracranial hypotension workup in the comatose patient and present a stepwise management algorithm to guide the appropriate diagnosis and treatment of these patients.

    View details for DOI 10.3171/2012.4.JNS112030

    View details for Web of Science ID 000307627100031

    View details for PubMedID 22725982

  • Stem cells and stroke: opportunities, challenges and strategies EXPERT OPINION ON BIOLOGICAL THERAPY Burns, T. C., Steinberg, G. K. 2011; 11 (4): 447-461

    Abstract

    Stroke remains the leading cause of disability in the Western world. Despite decades of work, no clinically effective therapies exist to facilitate recovery from stroke. Stem cells may have the potential to minimize injury and promote recovery after stroke. AREAS COVERED: Transplanted stem cells have been shown in animal models to migrate to the injured region, secrete neurotrophic compounds, promote revascularization, enhance plasticity and regulate the inflammatory response, thereby minimizing injury. Endogenous neural stem cells also have a remarkable propensity to respond to injury. Under select conditions, subventricular zone progenitors may be mobilized to replace lost neurons. In response to focal infarcts, neuroblasts play important trophic roles to minimize neural injury. Importantly, these endogenous repair mechanisms may be experimentally augmented, leading to robust improvements in function. Ongoing clinical studies are now assessing the safety and feasibility of cell-based therapies for stroke. EXPERT OPINION: We outline the unique challenges and potential pitfalls in the clinical translation of stem cell research for stroke. We then detail what we believe to be the specific basic science and clinical strategies needed to overcome these challenges, fill remaining gaps in knowledge and facilitate development of clinically viable stem cell-based therapies for stroke.

    View details for DOI 10.1517/14712598.2011.552883

    View details for Web of Science ID 000288221600002

    View details for PubMedID 21323594

  • Stem Cells for Ischemic Brain Injury: A Critical Review JOURNAL OF COMPARATIVE NEUROLOGY Burns, T. C., Verfaillie, C. M., Low, W. C. 2009; 515 (1): 125-144

    Abstract

    No effective therapy is currently available to promote recovery following ischemic stroke. Stem cells have been proposed as a potential source of new cells to replace those lost due to central nervous system injury, as well as a source of trophic molecules to minimize damage and promote recovery. We undertook a detailed review of data from recent basic science and preclinical studies to investigate the potential application of endogenous and exogenous stem cell therapies for treatment of cerebral ischemia. To date, spontaneous endogenous neurogenesis has been observed in response to ischemic injury, and can be enhanced via infusion of appropriate cytokines. Exogenous stem cells from multiple sources can generate neural cells that survive and form synaptic connections after transplantation in the stroke-injured brain. Stem cells from multiple sources cells also exhibit neuroprotective properties that may ameliorate stroke deficits. In many cases, functional benefits observed are likely independent of neural differentiation, although the exact mechanisms remain poorly understood. Future studies of neuroregeneration will require the demonstration of function in endogenously born neurons following focal ischemia. Further, methods are currently lacking to demonstrate definitively the therapeutic effect of newly introduced neural cells. Increased plasticity following stroke may facilitate the functional integration of new neurons, but the loss of appropriate guidance cues and supporting architecture in the infarct cavity will likely impede the restoration of lost circuitry. Thus careful investigation of the mechanisms underlying trophic benefits will be essential. Evidence to date suggests that continued development of stem cell therapies may ultimately lead to viable treatment options for ischemic brain injury.

    View details for DOI 10.1002/cne.22038

    View details for Web of Science ID 000266113700012

    View details for PubMedID 19399885

  • Detection of neuronal loss using T-1 rho MRI assessment of (H2O)-H-1 spin dynamics in the aphakia mouse JOURNAL OF NEUROSCIENCE METHODS Michaeli, S., Burns, T. C., Kudishevich, E., Harel, N., Hanson, T., Sorce, D. J., Garwood, M., Low, W. C. 2009; 177 (1): 160-167

    Abstract

    The loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) is well characterized in Parkinson's disease (PD). Recent developments in magnetic resonance imaging (MRI) techniques have provided the opportunity to evaluate for changes in cellular density. Longitudinal relaxation measurements in the rotating frame (T(1rho)) provide a unique magnetic resonance imaging contrast in vivo. Due to the specificity of T(1rho) to water-protein interactions, the T(1rho) MRI method has strong potential to be used as a non-invasive method for quantification of neuronal density in the brain. Recently introduced adiabatic T(1rho) magnetic resonance imaging mapping methods provide a tool to assess molecular motional regimes with high sensitivity due to utilization of an effective magnetic field sweep during adiabatic pulses. In this work, to investigate the sensitivity of T(1rho) to alterations in neuronal density, adiabatic T(1rho) MRI measurements were employed in vivo on Pitx3-homeobox gene-deficient aphakia mice in which the deficit of DA neurons in the SNc is well established. The theoretical analysis of T(1rho) maps in the different areas of the brain of aphakia mouse suggested variation of the (1)H(2)O rotational correlation times, tau(c). This suggests tau(c) to be a sensitive indicator for neuronal loss during neurological disorders. The results manifest significant dependencies of the T(1rho) relaxations on the cell densities in the SNc, suggesting T(1rho) MRI method as a candidate for detection of neuronal loss in neurological disorders.

    View details for DOI 10.1016/j.jneumeth.2008.10.025

    View details for Web of Science ID 000262706300019

    View details for PubMedID 19027791

  • Endovascular Interventions following Intravenous Thrombolysis May Improve Survival and Recovery in Patients with Acute Ischemic Stroke: A Case-Control Study AMERICAN JOURNAL OF NEURORADIOLOGY Burns, T. C., Rodriguez, G. J., Patel, S., Hussein, H. M., Georgiadis, A. L., Lakshminarayan, K., Qureshi, A. I. 2008; 29 (10): 1918-1924

    Abstract

    Since the introduction of recombinant tissue plasminogen activator (rtPA) into clinical practice in the mid 1990s, no adjunctive treatment has further improved clinical outcomes in patients with ischemic stroke. The safety, feasibility, and efficacy of combining intravenous (IV) rtPA with endovascular interventions has been described; however, no direct comparative study has yet established whether endovascular interventions after IV rtPA are superior to IV rtPA alone. A retrospective case-control study was designed to address this issue.Between 2003 and 2006, 33 consecutive patients with acute ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) scores >/=10 were treated with IV rtPA in combination with endovascular interventions (IV plus intervention) at a tertiary care facility. Outcomes were compared with a control cohort of 30 consecutive patients treated with IV rtPA (IV only) at a comparable facility where endovascular interventions were not available.Baseline parameters were similar between the 2 groups. We found that the IV-plus-intervention group experienced significantly lower mortality at 90 days (12.1% versus 40.0%, P = .019) with a significantly greater improvement in NIHSS scores by the time of discharge or follow-up (P = .025). In the IV-plus-intervention group, patients with admission NIHSS scores between 10 and 15 and patients /=10, there was a suggestion of incremental clinical benefit among patients receiving endovascular interventions following standard administration of IV rtPA.

    View details for DOI 10.3174/ajnr.A1236

    View details for Web of Science ID 000261072200022

    View details for PubMedID 18784214

  • Hematopoietic reconstitution by multipotent adult progenitor cells: precursors to long-term hematopoietic stem cells JOURNAL OF EXPERIMENTAL MEDICINE Serafini, M., Dylla, S. J., Oki, M., Heremans, Y., Tolar, J., Jiang, Y., Buckley, S. M., Pelacho, B., Burns, T. C., Frommer, S., Rossi, D. J., Bryder, D., Panoskaltsis-Mortari, A., O'Shaughnessy, M. J., Nelson-Holte, M., Fine, G. C., Weissman, I. L., Blazar, B. R., Verfaillie, C. M. 2007; 204 (1): 129-139

    Abstract

    For decades, in vitro expansion of transplantable hematopoietic stem cells (HSCs) has been an elusive goal. Here, we demonstrate that multipotent adult progenitor cells (MAPCs), isolated from green fluorescent protein (GFP)-transgenic mice and expanded in vitro for >40-80 population doublings, are capable of multilineage hematopoietic engraftment of immunodeficient mice. Among MAPC-derived GFP+CD45.2+ cells in the bone marrow of engrafted mice, HSCs were present that could radioprotect and reconstitute multilineage hematopoiesis in secondary and tertiary recipients, as well as myeloid and lymphoid hematopoietic progenitor subsets and functional GFP+ MAPC-derived lymphocytes that were functional. Although hematopoietic contribution by MAPCs was comparable to control KTLS HSCs, approximately 10(3)-fold more MAPCs were required for efficient engraftment. Because GFP+ host-derived CD45.1+ cells were not observed, fusion is not likely to account for the generation of HSCs by MAPCs.

    View details for DOI 10.1084/jem.20061115

    View details for Web of Science ID 000243753600017

    View details for PubMedID 17227908

  • Heparan sulfate mediates neuroprotection from degeneration in experimental glutaric aciduria CELL TRANSPLANTATION Naylor, M. C., Negia, M., Noetzel, M., Burns, T. C., Demorest, Z. L., Low, W. C. 2007; 16 (3): 187-195

    Abstract

    Glutaric aciduria type 1 (GA1) is a childhood metabolic disorder associated with crises that lead to striatal necrosis. Although the disorder can be controlled with diet, there is no current treatment to ameliorate the neurodegeneration following a metabolic crisis. We hypothesized that heparan sulfate (HS) administration would stimulate neural stem cell proliferation by dimerizing with FGF-2 and binding to the FGF-2 receptor on neural stem cells, thus enhancing the number of newly generated neurons to repair damage following a metabolic crisis. In addition, FGF-2 is known to exert neuroprotective effects independent of neurogenesis, so HS may also have neuroprotective activities. To test these hypotheses, ibotenic acid was injected into the striatum of adult mice, mimicking the metabolic crisis and damage caused by glutaric aciduria. Daily doses of HS and bromodeoxyuridine (BrdU) or BrdU alone were administered starting 1 day after the ibotenic acid lesion. BrdU was used to label dividing cells. Fluorescent immunohistochemistry was used to quantify the lesion size and evaluate the phenotype of BrdU-positive cells. Intrastriatal administration of ibotenic acid resulted in a substantial striatal lesion that occupied 18.5% of the ipsilateral brain hemisphere. In contrast, animals treated with HS exhibited a lesion volume representing <1% of the ipsilateral brain hemisphere (ANOVA; p < 0.0001). Increased neurogenesis, however, was not observed in this group. These results suggest that HS administration 2 days after a "metabolic crisis" can ameliorate brain injury in an animal model of GA1. The neuroprotective mechanisms of HS, however, remain to be elucidated but may exert their actions indirectly through binding with FGF-2.

    View details for Web of Science ID 000246167200002

    View details for PubMedID 17503732

  • Transcriptional characterization of the notch signaling pathway in rodent multipotent adult progenitor cells PATHOLOGY & ONCOLOGY RESEARCH Hajdu, M., Luttun, A., Pelacho, B., Burns, T. C., Chase, L., Gutierrez-Perez, M., Jiang, Y., Lenvik, T., Vas, V., Uher, F., Sebestyen, A., Verfaillie, C. 2007; 13 (4): 302-310

    Abstract

    The Notch signaling pathway is a multifunctional, evolutionarily conserved pathway, which plays an important role in development as well as stem cell biology. Multipotent adult progenitor cells (MAPCs) represent a unique stem cell population, which is capable of differentiating into cell types of the ectodermal, mesodermal and endodermal lineages in vitro, and contribute to most somatic cell types in vivo. Our aim was to characterize the gene expression of Notch signaling elements in rodent MAPCs. We show that transcripts for Notch-receptors, ligands, regulatory molecules of the pathway and the Hairy/Enhancer of Split-1 (HES-1) target gene are present in mouse and rat low-Oct4 MAPCs. We found that mouse Notch3 and rat Notch1 transcripts increased when cells were cultured at high density for 48 to 96 hours. HES-1 and HES-related transcription factor-1 (HERP-1), transcriptional targets of Notch-signaling, were both elicited by immobilized Delta1 ligand. In addition, mRNA for Notch1 and Notch3 was also induced by Notch-signaling, suggesting the presence of regulatory feedback loops. Slight differences between mouse and rat derived MAPCs suggest that the exact function, transcriptional regulation and the fine-tuning of the signal may be species specific. Taken together, we characterized the gene expression profile of the Notch pathway in rodent low-Oct4-MAPCs, and showed that the pathway is functional and can be modulated. Our results provide an additional tool and a further basis for a better understanding of stem cell biology.

    View details for Web of Science ID 000253082900006

    View details for PubMedID 18158565

  • Thymidine analogs are transferred from prelabeled donor to host cells in the central nervous system after transplantation: A word of caution STEM CELLS Burns, T. C., Ortiz-Gonzalez, X. R., Gutierrez-Perez, M., Keene, C. D., Sharda, R., Demorest, Z. L., Jiang, Y., Nelson-Holte, M., Soriano, M., Nakagawa, Y., Luquin, M. R., Garcia-Verdugo, J. M., Prosper, F., Low, W. C., Verfaillie, C. M. 2006; 24 (4): 1121-1127

    Abstract

    Thymidine analogs, including bromodeoxyuridine, chlorodeoxyuridine, iododeoxyuridine, and tritiated thymidine, label dividing cells by incorporating into DNA during S phase of cell division and are widely employed to identify cells transplanted into the central nervous system. However, the potential for transfer of thymidine analogs from grafted cells to dividing host cells has not been thoroughly tested. We here demonstrate that graft-derived thymidine analogs can become incorporated into host neural precursors and glia. Large numbers of labeled neurons and glia were found 3-12 weeks after transplantation of thymidine analog-labeled live stem cells, suggesting differentiation of grafted cells. Remarkably, however, similar results were obtained after transplantation of dead cells or labeled fibroblasts. Our findings reveal for the first time that thymidine analog labeling may not be a reliable means of identifying transplanted cells, particularly in highly proliferative environments such as the developing, neurogenic, or injured brain.

    View details for DOI 10.1634/stemcells.2005-0463

    View details for Web of Science ID 000240636300035

    View details for PubMedID 16373692

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