Bio

Clinical Focus


  • Pediatric Neurosurgery
  • Brain Tumors
  • Surgical epilepsy
  • Neuroendoscopy
  • Arnold-Chiari Malformation
  • Minimally invasive craniosynostosis
  • Moya-moya disease

Academic Appointments


Administrative Appointments


  • Division Chief, Pediatric Neurosurgery (2014 - Present)

Boards, Advisory Committees, Professional Organizations


  • Section Editor, Neurosurgery (2014 - Present)
  • Education Chair, American Society of Pediatric Neurosurgery (2013 - Present)
  • Committee on Trauma, American College of Surgeons (2012 - Present)
  • Member at Large, Executive Commitee, Section of Pediatric Neurosurgery (2014 - Present)
  • Executive Committee, Congress of Neurological Surgeons (2014 - Present)

Professional Education


  • Board Certification: Pediatric Neurological Surgery, American Board of Pediatric Neurological Surgery (2008)
  • Fellowship:University of Washington (2002) WA
  • Residency:University of Washington (2001) WA
  • Internship:University of Washington (1995) WA
  • Board Certification: Neurological Surgery, American Board of Neurological Surgery (2005)
  • Medical Education:Stanford University School of Medicine (1994) CA
  • Bachelor of Sciences, Duke University, Neurosciences (1989)

Community and International Work


  • Stanford Neurosurgery in Uganda, Mulago Hospital

    Topic

    Pediatric Neurosurgery/Endoscopy

    Partnering Organization(s)

    Duke University

    Populations Served

    Uganda

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

Research & Scholarship

Current Research and Scholarly Interests


Dr. Grant directs a Blood-brain Barrier Translational Laboratory focusing on enhancing drug delivery to brain tumors in children.

Teaching

2014-15 Courses


Publications

Journal Articles


  • Therapeutic strategies to improve drug delivery across the blood-brain barrier. Neurosurgical focus Azad, T. D., Pan, J., Connolly, I. D., Remington, A., Wilson, C. M., Grant, G. A. 2015; 38 (3): E9-?

    Abstract

    Resection of brain tumors is followed by chemotherapy and radiation to ablate remaining malignant cell populations. Targeting these populations stands to reduce tumor recurrence and offer the promise of more complete therapy. Thus, improving access to the tumor, while leaving normal brain tissue unscathed, is a critical pursuit. A central challenge in this endeavor lies in the limited delivery of therapeutics to the tumor itself. The blood-brain barrier (BBB) is responsible for much of this difficulty but also provides an essential separation from systemic circulation. Due to the BBB's physical and chemical constraints, many current therapies, from cytotoxic drugs to antibody-based proteins, cannot gain access to the tumor. This review describes the characteristics of the BBB and associated changes wrought by the presence of a tumor. Current strategies for enhancing the delivery of therapies across the BBB to the tumor will be discussed, with a distinction made between strategies that seek to disrupt the BBB and those that aim to circumvent it.

    View details for DOI 10.3171/2014.12.FOCUS14758

    View details for PubMedID 25727231

  • Sertraline-induced potentiation of the CYP3A4-dependent neurotoxicity of carbamazepine: An in vitro study EPILEPSIA Ghosh, C., Hossain, M., Spriggs, A., Ghosh, A., Grant, G. A., Marchi, N., Perucca, E., Janigro, D. 2015; 56 (3): 439-449

    Abstract

    Drug toxicity is a hurdle to drug development and to clinical translation of basic research. Antiepileptic drugs such as carbamazepine (CBZ) and selective serotonin reuptake inhibitors such as sertraline (SRT) are commonly co-prescribed to patients with epilepsy and comorbid depression. Because SRT may interfere with cytochrome P450 (CYP) enzyme activity and CYPs have been implicated in the conversion of CBZ to reactive cytotoxic metabolites, we investigated in vitro models to determine whether SRT affects the neurotoxic potential of CBZ and the mechanisms involved.Human fetal brain-derived dopaminergic neurons, human brain microvascular endothelial cells (HBMECs), and embryonic kidney (HEK) cells were used to evaluate cytotoxicity of CBZ and SRT individually and in combination. Nitrite and glutathione (GSH) levels were measured with drug exposure. To validate the role of CYP3A4 in causing neurotoxicity, drug metabolism was compared to cell death in HEK CYP3A4 overexpressed and cells pretreated with the CYP3A4 inhibitor ketoconazole.In all cellular systems tested, exposure to CBZ (127 μm) or SRT (5 μm) alone caused negligible cytotoxicity. By contrast CBZ, tested at a much lower concentration (17 μm) in combination with SRT (5 μm), produced prominent cytotoxicity within 15 min exposure. In neurons and HBMECs, cytotoxicity was associated with increased nitrite levels, suggesting involvement of free radicals as a pathogenetic mechanism. Pretreatment of HBMECs with reduced GSH or with the GSH precursor N-acetyl-l-cysteine prevented cytotoxic response. In HEK cells, the cytotoxic response to the CBZ + SRT combination correlated with the rate of CBZ biotransformation and production of 2-hydroxy CBZ, further suggesting a causative role of reactive metabolites. In the same system, cytotoxicity was potentiated by overexpression of CYP3A4, and prevented by CYP3A4 inhibitor.These results demonstrate an unexpected neurotoxic interaction between CBZ and SRT, apparently related to increased CYP3A4-mediated production of reactive CBZ metabolites. The potential clinical implications of these findings are discussed.

    View details for DOI 10.1111/epi.12923

    View details for Web of Science ID 000351240300016

    View details for PubMedID 25656284

  • Joint eQTL assessment of whole blood and dura mater tissue from individuals with Chiari type I malformation BMC GENOMICS Lock, E. F., Soldano, K. L., Garrett, M. E., Cope, H., Markunas, C. A., Fuchs, H., Grant, G., Dunson, D. B., Gregory, S. G., Ashley-Koch, A. E. 2015; 16
  • Is there a role for decompressive craniectomy in children after stroke? World neurosurgery Grant, G. A. 2015; 83 (1): 44-45

    View details for DOI 10.1016/j.wneu.2013.08.049

    View details for PubMedID 24012655

  • Preface to clinical neurosurgery volume 61, proceedings of the congress of neurological surgeons 2013 annual meeting. Neurosurgery Grant, G. A., Hankinson, T., Muh, C., Dumont, A., Cheshier, S. 2014; 61: N1-?

    View details for DOI 10.1227/NEU.0000000000000442

    View details for PubMedID 25032656

  • Identification of Chiari Type I Malformation subtypes using whole genome expression profiles and cranial base morphometrics BMC MEDICAL GENOMICS Markunas, C. A., Lock, E., Soldano, K., Cope, H., Ding, C. C., Enterline, D. S., Grant, G., Fuchs, H., Ashley-Koch, A. E., Gregory, S. G. 2014; 7
  • Genome Sequencing of SHH Medulloblastoma Predicts Genotype-Related Response to Smoothened Inhibition CANCER CELL Kool, M., Jones, D. T., Jaeger, N., Northcott, P. A., Pugh, T. J., Hovestadt, V., Piro, R. M., Esparza, L. A., Markant, S. L., Remke, M., Milde, T., Bourdeaut, F., Ryzhova, M., Sturm, D., Pfaff, E., Stark, S., Hutter, S., Seker-Cin, H., Johann, P., Bender, S., Schmidt, C., Rausch, T., Shih, D., Reimand, J., Sieber, L., Wittmann, A., Linke, L., Witt, H., Weber, U. D., Zapatka, M., Koenig, R., Beroukhim, R., Bergthold, G., Van Sluis, P., Volckmann, R., Koster, J., Versteeg, R., Schmidt, S., Wolf, S., Lawerenz, C., Bartholomae, C. C., von Kalle, C., Unterberg, A., Herold-Mende, C., Hofer, S., Kulozik, A. E., von Deimling, A., Scheurlen, W., Felsberg, J., Reifenberger, G., Hasselblatt, M., Crawford, J. R., Grant, G. A., Jabado, N., Perry, A., Cowdrey, C., Croul, S., Zadeh, G., Korbel, J. O., Doz, F., Delattre, O., Bader, G. D., McCabe, M. G., Collins, V. P., Kieran, M. W., Cho, Y., Pomeroy, S. L., Witt, O., Brors, B., Taylor, M. D., Schueller, U., Korshunov, A., Eils, R., Wechsler-Reya, R. J., Lichter, P., Pfister, S. M. 2014; 25 (3): 393-405

    Abstract

    Smoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large cohort of SHH-MBs (n = 133). SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 years old harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often in the germline, all of which were rare in infants and adults. Functional assays in different SHH-MB xenograft models demonstrated that SHH-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant.

    View details for DOI 10.1016/j.ccr.2014.02.004

    View details for Web of Science ID 000333233400015

    View details for PubMedID 24651015

  • Reorganization and stability for motor and language areas using cortical stimulation: case example and review of the literature. Brain sciences Serafini, S., Komisarow, J. M., Gallentine, W., Mikati, M. A., Bonner, M. J., Kranz, P. G., Haglund, M. M., Grant, G. 2013; 3 (4): 1597-1614

    Abstract

    The cerebral organization of language in epilepsy patients has been studied with invasive procedures such as Wada testing and electrical cortical stimulation mapping and more recently with noninvasive neuroimaging techniques, such as functional MRI. In the setting of a chronic seizure disorder, clinical variables have been shown to contribute to cerebral language reorganization underscoring the need for language lateralization and localization procedures. We present a 14-year-old pediatric patient with a refractory epilepsy disorder who underwent two neurosurgical resections of a left frontal epileptic focus separated by a year. He was mapped extraoperatively through a subdural grid using cortical stimulation to preserve motor and language functions. The clinical history and extensive workup prior to surgery is discussed as well as the opportunity to compare the cortical maps for language, motor, and sensory function before each resection. Reorganization in cortical tongue sensory areas was seen concomitant with a new zone of ictal and interictal activity in the previous tongue sensory area. Detailed neuropsychological data is presented before and after any surgical intervention to hypothesize about the extent of reorganization between epochs. We conclude that intrahemispheric cortical plasticity does occur following frontal lobe resective surgery in a teenager with medically refractory seizures.

    View details for DOI 10.3390/brainsci3041597

    View details for PubMedID 24961623

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