Bio

Bio


Stroke is the leading cause of disability in the United States, drastically disrupting the lives of stroke survivors and their caretakers. Unfortunately, because of tight therapeutic time requirements, the majority of stroke patients are not eligible for the current medicines or interventions. The George Lab's research focuses on improving stroke diagnostics as well as engineering new methods to enhance stroke recovery. Our lab's primary focus is applying novel bioengineering techniques to understand the mechanisms of neural recovery (primarily in stroke) and discovering methods to improve patient recovery. We use rodent models of stroke combined with biomaterial techniques, stem cell transplants, and microfabrication to achieve these aims and evaluate our methods with behavior testing and various imaging techniques. Our ultimate goal is to translate these findings into clinical trials to help stroke patients.

Clinical Focus


  • Neurology

Academic Appointments


Administrative Appointments


  • Neuroscience PhD Program Representative, Committee on Graduate Admissions and Policy (2017 - Present)

Boards, Advisory Committees, Professional Organizations


  • Science Committee, American Academy of Neurology (2013 - Present)

Professional Education


  • Fellowship:Stanford University Vascular Neurology Fellowship (2013) CA
  • Residency:Stanford University Neurology Residency (2012) CA
  • Internship:Stanford University Internal Medicine Residency Training (2009) CA
  • Board Certification: Vascular Neurology, American Board of Psychiatry and Neurology (2014)
  • Board Certification: Neurology, American Board of Psychiatry and Neurology (2012)
  • Medical Education:Harvard Medical School (2008) MA
  • PhD, Massachussetts Institute of Technology, Electrical and Medical Engineering (2005)
  • BSE, Tulane University of Louisiana (1999)

Research & Scholarship

Current Research and Scholarly Interests


CONDUCTIVE POLYMER SCAFFOLDS FOR STEM CELL-ENHANCED STROKE RECOVERY:
We focus on developing conductive polymers for stem cell applications. We have created a microfabricated, polymeric system that can continuously interact with its biological environment. This interactive polymer platform allows modifications of the recovery environment to determine essential repair mechanisms. Recent work studies the effect of electrical stimulation on neural stem cells seeded on the conductive scaffold and the pathways by which it enhances stroke recovery Further understanding the combined effect of electrical stimulation and stem cells in augmenting neural repair for clinical translational is a major focus of this research going forward.

BIOPOLYMER SYSTEMS FOR NEURAL RECOVERY AND STEM CELL MODULATION:
The George lab develops biomaterials to improve neural recovery in the peripheral and central nervous systems. By controlled release of drugs and molecules through biomaterials we can study the temporal effect of these neurotrophic factors on neural recovery and engineer drug delivery systems to enhance regenerative effects. By identifying the critical mechanisms for stroke and neural recovery, we are able to develop polymeric technologies for clinical translation in nerve regeneration and stroke recovery. Recent work utilizing these novel conductive polymers to differentiate stem cells for therapeutic and drug discovery applications.

APPLYING ENGINEERING TECHNIQUES TO DETERMINE BIOMARKERS FOR STROKE DIAGNOSTICS:
The ability to create diagnostic assays and techniques enables us to understand biological systems more completely and improve clinical management. Previous work utilized mass spectroscopy proteomics to find a simple serum biomarker for TIAs (a warning sign of stroke). Our study discovered a novel candidate marker, platelet basic protein. Current studies are underway to identify further candidate biomarkers using transcriptome analysis. More accurate diagnosis will allow for aggressive therapies to prevent subsequent strokes.

Clinical Trials


  • Transient Ischemic Attack (TIA) Triage and Evaluation of Stroke Risk Not Recruiting

    Transient ischemic attack (TIA) is a transient neurological deficit (speech disturbance, weakness…), caused by temporary occlusion of a brain vessel by a blood clot that leaves no lasting effect. TIA diagnosis can be challenging and an expert stroke evaluation combined with magnetic resonance imaging (MRI) could improve the diagnosis accuracy. The risk of a debilitating stroke can be as high as 5% during the first 72 hrs after TIA. TIA characteristics (duration, type of symptoms, age of the patient), the presence of a significant narrowing of the neck vessels responsible for the patient's symptoms (symptomatic stenosis), and an abnormal MRI are associated with an increased risk of stroke. An emergent evaluation and treatment of TIA patients by a stroke specialist could reduce the risk of stroke to 2%. Stanford has implemented an expedited triage pathway for TIA patients combining a clinical evaluation by a stroke neurologist, an acute MRI of the brain and the vessels and a sampling of biomarkers (Lp-PLA2). The investigators are investigating the yield of this unique approach to improve TIA diagnosis, prognosis and secondary stroke prevention. The objective of this prospective cohort study is to determine which factors will help the physician to confirm the diagnosis of TIA and to define the risk of stroke after a TIA.

    Stanford is currently not accepting patients for this trial. For more information, please contact Stephanie Kemp, BS, 650-723-4481.

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  • Imaging Collaterals in Acute Stroke (iCAS) Recruiting

    Stroke is caused by a sudden blockage of a blood vessel that delivers blood to the brain. Unblocking the blood vessel with a blood clot removal device restores blood flow and if done quickly may prevent the disability that can be caused by a stroke. However, not all stroke patients benefit from having their blood vessel unblocked. The aim of this study is to determine if special brain imaging, called MRI, can be used to identify which stroke patients are most likely to benefit from attempts to unblock their blood vessel with a special blood clot removal device. In particular, we will assess in this trial whether a noncontrast MR imaging sequence, arterial spin labeling (ASL), can demonstrate the presence of collateral blood flow (compared with a gold standard of the angiogram) and whether it is useful to predict who will benefit from treatment.

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Teaching

2018-19 Courses


Stanford Advisees


Graduate and Fellowship Programs


Publications

All Publications


  • Engineered stem cell mimics to enhance stroke recovery. Biomaterials George, P. M., Oh, B., Dewi, R., Hua, T., Cai, L., Levinson, A., Liang, X., Krajina, B. A., Bliss, T. M., Heilshorn, S. C., Steinberg, G. K. 2018; 178: 63–72

    Abstract

    Currently, no medical therapies exist to augment stroke recovery. Stem cells are an intriguing treatment option being evaluated, but cell-based therapies have several challenges including developing a stable cell product with long term reproducibility. Since much of the improvement observed from cellular therapeutics is believed to result from trophic factors the stem cells release over time, biomaterials are well-positioned to deliver these important molecules in a similar fashion. Here we show that essential trophic factors secreted from stem cells can be effectively released from a multi-component hydrogel system into the post-stroke environment. Using our polymeric system to deliver VEGF-A and MMP-9, we improved recovery after stroke to an equivalent degree as observed with traditional stem cell treatment in a rodent model. While VEGF-A and MMP-9 have many unique mechanisms of action, connective tissue growth factor (CTGF) interacts with both VEGF-A and MMP-9. With our hydrogel system as well as with stem cell delivery, the CTGF pathway is shown to be downregulated with improved stroke recovery.

    View details for DOI 10.1016/j.biomaterials.2018.06.010

    View details for PubMedID 29909038

  • Electrically Conductive Scaffold to Modulate and Deliver Stem Cells. Journal of visualized experiments : JoVE Oh, B., Levinson, A., Lam, V., Song, S., George, P. 2018

    Abstract

    Stem cell therapy has emerged as an exciting stroke therapeutic, but the optimal delivery method remains unclear. While the technique of microinjection has been used for decades to deliver stem cells in stroke models, this technique is limited by the lack of ability to manipulate the stem cells prior to injection. This paper details a method of using an electrically conductive polymer scaffold for stem cell delivery. Electrical stimulation of stem cells using a conductive polymer scaffold alters the stem cell's genes involved in cell survival, inflammatory response, and synaptic remodeling. After electrical preconditioning, the stem cells on the scaffold are transplanted intracranially in a distal middle cerebral artery occlusion rat model. This protocol describes a powerful technique to manipulate stem cells via a conductive polymer scaffold and creates a new tool to further develop stem cell-based therapy.

    View details for DOI 10.3791/57367

    View details for PubMedID 29708538

  • Electrical preconditioning of stem cells with a conductive polymer scaffold enhances stroke recovery. Biomaterials George, P. M., Bliss, T. M., Hua, T., Lee, A., Oh, B., Levinson, A., Mehta, S., Sun, G., Steinberg, G. K. 2017; 142: 31–40

    Abstract

    Exogenous human neural progenitor cells (hNPCs) are promising stroke therapeutics, but optimal delivery conditions and exact recovery mechanisms remain elusive. To further elucidate repair processes and improve stroke outcomes, we developed an electrically conductive, polymer scaffold for hNPC delivery. Electrical stimulation of hNPCs alters their transcriptome including changes to the VEGF-A pathway and genes involved in cell survival, inflammatory response, and synaptic remodeling. In our experiments, exogenous hNPCs were electrically stimulated (electrically preconditioned) via the scaffold 1 day prior to implantation. After in vitro stimulation, hNPCs on the scaffold are transplanted intracranially in a distal middle cerebral artery occlusion rat model. Electrically preconditioned hNPCs improved functional outcomes compared to unstimulated hNPCs or hNPCs where VEGF-A was blocked during in vitro electrical preconditioning. The ability to manipulate hNPCs via a conductive scaffold creates a new approach to optimize stem cell-based therapy and determine which factors (such as VEGF-A) are essential for stroke recovery.

    View details for DOI 10.1016/j.biomaterials.2017.07.020

    View details for PubMedID 28719819

  • Conductive polymer scaffolds to improve neural recovery. Neural regeneration research Song, S., George, P. M. 2017; 12 (12): 1976–78

    View details for DOI 10.4103/1673-5374.221151

    View details for PubMedID 29323032

    View details for PubMedCentralID PMC5784341

  • Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischaemic attack: a pooled analysis of individual-patient data from cohort studies LANCET NEUROLOGY Kelly, P. J., Albers, G. W., Chatzikonstantinou, A., De Marchis, G. M., Ferrari, J., George, P., Katan, M., Knoflach, M., Kim, J. S., Li, L., Lee, E., Olivot, J., Purroy, F., Raposo, N., Rothwell, P. M., Sharma, V. K., Song, B., Tsivgoulis, G., Walsh, C., Xu, Y., Merwick, A. 2016; 15 (12): 1236-1245
  • Inter-rater agreement analysis of the Precise Diagnostic Score for suspected transient ischemic attack. International journal of stroke Cereda, C. W., George, P. M., Inoue, M., Vora, N., Olivot, J., Schwartz, N., Lansberg, M. G., Kemp, S., Mlynash, M., Albers, G. W. 2016; 11 (1): 85-92

    Abstract

    No definitive criteria are available to confirm the diagnosis of transient ischemic attack. Inter-rater agreement between physicians regarding the diagnosis of transient ischemic attack is low, even among vascular neurologists. We developed the Precise Diagnostic Score, a diagnostic score that consists of discrete and well-defined clinical and imaging parameters, and investigated inter-rater agreement in patients with suspected transient ischemic attack.Fellowship-trained vascular neurologists, blinded to final diagnosis, independently reviewed retrospectively identical history, physical examination, routine diagnostic studies, and brain magnetic resonance imaging (diffusion and perfusion images) from consecutive patients with suspected transient ischemic attack. Each patient was rated using the 8-point Precise Diagnostic Score score, composed of a clinical score (0-4 points) and an imaging score (0-4 points). The composite Precise Diagnostic Score determines a Precise Diagnostic Score Likelihood of Brain Ischemia Scale: 0-1 = unlikely, 2 = possible, 3 = probable, 4-8 = very likely.Three raters reviewed data from 114 patients. Using Precise Diagnostic Score, all three raters scored a similar percentage of the clinical events as being "probable" or "very likely" caused by brain ischemia: 57, 55, and 58%. Agreement was high for both total Precise Diagnostic Score (intraclass correlation coefficient of 0.94) and for the Likelihood of Brain Ischemia Scale (agreement coefficient of 0.84).Compared with prior studies, inter-rater agreement for the diagnosis of transient brain ischemia appears substantially improved with the Precise Diagnostic Score scoring system. This score is the first to include specific criteria to assess the clinical relevance of diffusion-weighted imaging and perfusion lesions and supports the added value of magnetic resonance imaging for assessing patients with suspected transient ischemic attack.

    View details for DOI 10.1177/1747493015607507

    View details for PubMedID 26763024

  • Novel TIA biomarkers identified by mass spectrometry-based proteomics INTERNATIONAL JOURNAL OF STROKE George, P. M., Mlynash, M., Adams, C. M., Kuo, C. J., Albers, G. W., Olivot, J. 2015; 10 (8): 1204-1211

    View details for DOI 10.1111/ijs.12603

    View details for Web of Science ID 000367673700011

  • Novel Stroke Therapeutics: Unraveling Stroke Pathophysiology and Its Impact on Clinical Treatments. Neuron George, P. M., Steinberg, G. K. 2015; 87 (2): 297-309

    Abstract

    Stroke remains a leading cause of death and disability in the world. Over the past few decades our understanding of the pathophysiology of stroke has increased, but greater insight is required to advance the field of stroke recovery. Clinical treatments have improved in the acute time window, but long-term therapeutics remain limited. Complex neural circuits damaged by ischemia make restoration of function after stroke difficult. New therapeutic approaches, including cell transplantation or stimulation, focus on reestablishing these circuits through multiple mechanisms to improve circuit plasticity and remodeling. Other research targets intact networks to compensate for damaged regions. This review highlights several important mechanisms of stroke injury and describes emerging therapies aimed at improving clinical outcomes.

    View details for DOI 10.1016/j.neuron.2015.05.041

    View details for PubMedID 26182415

  • Beneficial effects of a semi-intensive stroke unit are beyond the monitor. Cerebrovascular diseases Cereda, C. W., George, P. M., Pelloni, L. S., Gandolfi-Decristophoris, P., Mlynash, M., Biancon Montaperto, L., Limoni, C., Stojanova, V., Malacrida, R., Städler, C., Bassetti, C. L. 2015; 39 (2): 102-109

    Abstract

    Precise mechanisms underlying the effectiveness of the stroke unit (SU) are not fully established. Studies that compare monitored stroke units (semi-intensive type, SI-SU) versus an intensive care unit (ICU)-based mobile stroke team (MST-ICU) are lacking. Although inequalities in access to stroke unit care are globally improving, acute stroke patients may be admitted to Intensive Care Units for monitoring and followed by a mobile stroke team in hospital's lacking an SU with continuous cardiovascular monitoring. We aimed at comparing the stroke outcome between SI-SU and MST-ICU and hypothesized that the benefits of SI-SU are driven by additional elements other than cardiovascular monitoring, which is equally offered in both care systems.In a single-center setting, we compared the unfavorable outcomes (dependency and mortality) at 3 months in consecutive patients with ischemic stroke or spontaneous intracerebral hemorrhage admitted to a stroke unit with semi-intensive monitoring (SI-SU) to a cohort of stroke patients hospitalized in an ICU and followed by a mobile stroke team (MST-ICU) during an equal observation period of 27 months. Secondary objectives included comparing mortality and the proportion of patients with excellent outcomes (modified Rankin Score (mRS) 0-1). Equal cardiovascular monitoring was offered in patients admitted in both SI-SU and MST-ICU.458 patients were treated in the SI-SU and compared to the MST-ICU (n = 370) cohort. The proportion of death and dependency after 3 months was significantly improved for patients in the SI-SU compared to MST-ICU (p < 0.001; aOR = 0.45; 95% CI: 0.31-0.65). The shift analysis of the mRS distribution showed significant shift to the lower mRS in the SI-SU group, p < 0.001. The proportion of mortality in patients after 3 months also differed between the MST-ICU and the SI-SU (p < 0.05), but after adjusting for confounders this association was not significant (aOR = 0.59; 95% CI: 0.31-1.13). The proportion of patients with excellent outcome was higher in the SI-SU (59.4 vs. 44.9%, p < 0.001) but the relationship was no more significant after adjustment (aOR = 1.17; 95% CI: 0.87-1.5).Our study shows that moving from a stroke team in a monitored setting (ICU) to an organized stroke unit leads to a significant reduction in the 3 months unfavorable outcome in patients with an acute ischemic or hemorrhagic stroke. Cardiovascular monitoring is indispensable, but benefits of a semi-intensive Stroke Unit are driven by additional elements beyond intensive cardiovascular monitoring. This observation supports the ongoing development of Stroke Centers for efficient stroke care.

    View details for DOI 10.1159/000369919

    View details for PubMedID 25634579

  • Aortic arch atheroma: a plaque of a different color or more of the same? Stroke; a journal of cerebral circulation George, P. M., Albers, G. W. 2014; 45 (5): 1239-1240

    View details for DOI 10.1161/STROKEAHA.114.004827

    View details for PubMedID 24699053

  • Three-dimensional conductive constructs for nerve regeneration. Journal of biomedical materials research. Part A George, P. M., Saigal, R., Lawlor, M. W., Moore, M. J., LaVan, D. A., Marini, R. P., Selig, M., Makhni, M., Burdick, J. A., Langer, R., Kohane, D. S. 2009; 91 (2): 519-527

    Abstract

    The unique electrochemical properties of conductive polymers can be utilized to form stand-alone polymeric tubes and arrays of tubes that are suitable for guides to promote peripheral nerve regeneration. Noncomposite, polypyrrole (PPy) tubes ranging in inner diameter from 25 microm to 1.6 mm as well as multichannel tubes were fabricated by electrodeposition. While oxidation of the pyrrole monomer causes growth of the film, brief subsequent reduction allowed mechanical dissociation from the electrode mold, creating a stand-alone, conductive PPy tube. Conductive polymer nerve guides made in this manner were placed in transected rat sciatic nerves and shown to support nerve regeneration over an 8-week time period.

    View details for DOI 10.1002/jbm.a.32226

    View details for PubMedID 18985787

  • Electrically Controlled Drug Delivery from Biotin-Doped Conductive Polymer Advanced Materials George, P. M., LaVan, D., Burdick, J., Chen, C. Y., Liang, E., Langer, R. 2006; 18 (5)
  • Fabrication and biocompatibility of polypyrrole implants suitable for neural prosthetics BIOMATERIALS George, P. M., Lyckman, A. W., LaVan, D. A., Hegde, A., Leung, Y., Avasare, R., Testa, C., Alexander, P. M., Langer, R., Sur, M. 2005; 26 (17): 3511-3519

    Abstract

    Finding a conductive substrate that promotes neural interactions is an essential step for advancing neural interfaces. The biocompatibility and conductive properties of polypyrrole (PPy) make it an attractive substrate for neural scaffolds, electrodes, and devices. Stand-alone polymer implants also provide the additional advantages of flexibility and biodegradability. To examine PPy biocompatibility, dissociated primary cerebral cortical cells were cultured on PPy samples that had been doped with polystyrene-sulfonate (PSS) or sodium dodecylbenzenesulfonate (NaDBS). Various conditions were used for electrodeposition to produce different surface properties. Neural networks grew on all of the PPy surfaces. PPy implants, consisting of the same dopants and conditions, were surgically implanted in the cerebral cortex of the rat. The results were compared to stab wounds and Teflon implants of the same size. Quantification of the intensity and extent of gliosis at 3- and 6-week time points demonstrated that all versions of PPy were at least as biocompatible as Teflon and in fact performed better in most cases. In all of the PPy implant cases, neurons and glial cells enveloped the implant. In several cases, neural tissue was present in the lumen of the implants, allowing contact of the brain parenchyma through the implants.

    View details for DOI 10.1016/j.biomaterials.2004.09.037

    View details for Web of Science ID 000226968200016

    View details for PubMedID 15621241

  • Simple, three-dimensional microfabrication of electrodeposited structures ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LaVan, D. A., George, P. M., Langer, R. 2003; 42 (11): 1262-1265

    View details for Web of Science ID 000181872300008

    View details for PubMedID 12645058

  • Fabrication of Screen-Printed Carbon Electrode Arrays for Sensing Neuronal Messengers BIOMEDICAL MICRODEVICES George, P. M., Muthuswamy, J., Currie, J., Thakor, N. V., Paranjape, M. 2001; 3 (4): 307-313