Academic Appointments

  • Instructor, Neurology

Honors & Awards

  • Pediatric Cancer Fellowship, Damon Runyon-Sohn (2017-2021)
  • Fellowship Award, Stanford CHRI (2017-2018)
  • PhD Fellowship Award, Abbie's Army (2013-2015)
  • Pediatric Basic Science Award, WFNO/SNO (supported by the Pediatric Brain Tumor Foundation) (2013)

Professional Education

  • PhD, University of London : The Institute of Cancer Research, Neuro-oncology (2016)

All Publications

  • Glioma synapses recruit mechanisms of adaptive plasticity. Nature Taylor, K. R., Barron, T., Hui, A., Spitzer, A., Yalcin, B., Ivec, A. E., Geraghty, A. C., Hartmann, G. G., Arzt, M., Gillespie, S. M., Kim, Y. S., Maleki Jahan, S., Zhang, H., Shamardani, K., Su, M., Ni, L., Du, P. P., Woo, P. J., Silva-Torres, A., Venkatesh, H. S., Mancusi, R., Ponnuswami, A., Mulinyawe, S., Keough, M. B., Chau, I., Aziz-Bose, R., Tirosh, I., Suva, M. L., Monje, M. 2023


    The role of the nervous system in the regulation of cancer is increasingly appreciated. In gliomas, neuronal activity drives tumour progression through paracrine signalling factors such as neuroligin-3 and brain-derived neurotrophic factor1-3 (BDNF), and also through electrophysiologically functional neuron-to-glioma synapses mediated by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors4,5. The consequent glioma cell membrane depolarization drives tumour proliferation4,6. In the healthy brain, activity-regulated secretion of BDNF promotes adaptive plasticity of synaptic connectivity7,8 and strength9-15. Here we show that malignant synapses exhibit similar plasticity regulated by BDNF. Signalling through the receptor tropomyosin-related kinase B16 (TrkB) to CAMKII, BDNF promotes AMPA receptor trafficking to the glioma cell membrane, resulting in increased amplitude of glutamate-evoked currents in the malignant cells. Linking plasticity of glioma synaptic strength to tumour growth, graded optogenetic control of glioma membrane potential demonstrates that greater depolarizing current amplitude promotes increased glioma proliferation. This potentiation of malignant synaptic strength shares mechanistic features with synaptic plasticity17-22 that contributes to memory and learning in the healthy brain23-26. BDNF-TrkB signalling also regulates the number of neuron-to-glioma synapses. Abrogation of activity-regulated BDNF secretion from the brain microenvironment or loss of glioma TrkB expression robustly inhibits tumour progression. Blocking TrkB genetically or pharmacologically abrogates these effects of BDNF on glioma synapses and substantially prolongs survival in xenograft models of paediatric glioblastoma and diffuse intrinsic pontine glioma. Together, these findings indicate that BDNF-TrkB signalling promotes malignant synaptic plasticity and augments tumour progression.

    View details for DOI 10.1038/s41586-023-06678-1

    View details for PubMedID 37914930

  • Neuron-oligodendroglial interactions in health and malignant disease. Nature reviews. Neuroscience Taylor, K. R., Monje, M. 2023


    Experience sculpts brain structure and function. Activity-dependent modulation of the myelinated infrastructure of the nervous system has emerged as a dimension of adaptive change during childhood development and in adulthood. Myelination is a richly dynamic process, with neuronal activity regulating oligodendrocyte precursor cell proliferation, oligodendrogenesis and myelin structural changes in some axonal subtypes and in some regions of the nervous system. This myelin plasticity and consequent changes to conduction velocity and circuit dynamics can powerfully influence neurological functions, including learning and memory. Conversely, disruption of the mechanisms mediating adaptive myelination can contribute to cognitive impairment. The robust effects of neuronal activity on normal oligodendroglial precursor cells, a putative cellular origin for many forms of glioma, indicates that dysregulated or 'hijacked' mechanisms of myelin plasticity could similarly promote growth in this devastating group of brain cancers. Indeed, neuronal activity promotes the pathogenesis of many forms of glioma in preclinical models through activity-regulated paracrine factors and direct neuron-to-glioma synapses. This synaptic integration of glioma into neural circuits is central to tumour growth and invasion. Thus, not only do neuron-oligodendroglial interactions modulate neural circuit structure and function in the healthy brain, but neuron-glioma interactions also have important roles in the pathogenesis of glial malignancies.

    View details for DOI 10.1038/s41583-023-00744-3

    View details for PubMedID 37857838

    View details for PubMedCentralID 2791798

  • Remote neuronal activity drives glioma progression through SEMA4F. Nature Huang-Hobbs, E., Cheng, Y. T., Ko, Y., Luna-Figueroa, E., Lozzi, B., Taylor, K. R., McDonald, M., He, P., Chen, H. C., Yang, Y., Maleki, E., Lee, Z. F., Murali, S., Williamson, M. R., Choi, D., Curry, R., Bayley, J., Woo, J., Jalali, A., Monje, M., Noebels, J. L., Harmanci, A. S., Rao, G., Deneen, B. 2023


    The tumour microenvironment plays an essential role in malignancy, and neurons have emerged as a key component of the tumour microenvironment that promotes tumourigenesis across a host of cancers1,2. Recent studies on glioblastoma (GBM) highlight bidirectional signalling between tumours and neurons that propagates a vicious cycle of proliferation, synaptic integration and brain hyperactivity3-8; however, the identity of neuronal subtypes and tumour subpopulations driving this phenomenon is incompletely understood. Here we show that callosal projection neurons located in the hemisphere contralateral to primary GBM tumours promote progression and widespread infiltration. Using this platform to examine GBM infiltration, we identified an activity-dependent infiltrating population present at the leading edge of mouse and human tumours that is enriched for axon guidance genes. High-throughput, in vivo screening of these genes identified SEMA4F as a key regulator of tumourigenesis and activity-dependent progression. Furthermore, SEMA4F promotes the activity-dependent infiltrating population and propagates bidirectional signalling with neurons by remodelling tumour-adjacent synapses towards brain network hyperactivity. Collectively our studies demonstrate that subsets of neurons in locations remote to primary GBM promote malignant progression, and also show new mechanisms of glioma progression that are regulated by neuronal activity.

    View details for DOI 10.1038/s41586-023-06267-2

    View details for PubMedID 37380778

    View details for PubMedCentralID 7367763

  • GABAERGIC NEURON-TO-GLIOMA SYNAPSES IN DIFFUSE MIDLINE GLIOMAS Barron, T., Yalcin, B., Mochizuki, A., Cantor, E., Shamardani, K., Tlais, D., Franson, A., Lyons, S., Mehta, V., Jahan, S., Taylor, K., Keough, M., Xu, H., Su, M., Quezada, M., Woo, P., Fisher, P., Campen, C., Partap, S., Koschmann, C., Monje, M. OXFORD UNIV PRESS INC. 2023
  • Invasive glioma cells: The malignant pioneers that follow the current. Cell Taylor, K. R., Monje, M. 2022; 185 (16): 2846-2848


    Glioblastoma is a lethal, diffusely invasive brain cancer that is robustly regulated by the activity of the brain itself, in part through neuron-to-glioma synaptic communication. Venkataramani et al. have conceptually advanced understanding of glioblastoma interactions with neural circuits, demonstrating that conduction of electrochemical signals via neuron-to-glioma synapses drives glioma invasion.

    View details for DOI 10.1016/j.cell.2022.06.033

    View details for PubMedID 35931016

  • Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. Cell Fernández-Castañeda, A., Lu, P., Geraghty, A. C., Song, E., Lee, M. H., Wood, J., O'Dea, M. R., Dutton, S., Shamardani, K., Nwangwu, K., Mancusi, R., Yalçın, B., Taylor, K. R., Acosta-Alvarez, L., Malacon, K., Keough, M. B., Ni, L., Woo, P. J., Contreras-Esquivel, D., Toland, A. M., Gehlhausen, J. R., Klein, J., Takahashi, T., Silva, J., Israelow, B., Lucas, C., Mao, T., Peña-Hernández, M. A., Tabachnikova, A., Homer, R. J., Tabacof, L., Tosto-Mancuso, J., Breyman, E., Kontorovich, A., McCarthy, D., Quezado, M., Vogel, H., Hefti, M. M., Perl, D. P., Liddelow, S., Folkerth, R., Putrino, D., Nath, A., Iwasaki, A., Monje, M. 2022


    COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared with SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white-matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis, and elevated CCL11 at early time points, but after influenza, only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.

    View details for DOI 10.1016/j.cell.2022.06.008

    View details for PubMedID 35768006

  • How Support of Early Career Researchers Can Reset Science in the Post-COVID19 World. Cell Gibson, E. M., Bennett, F. C., Gillespie, S. M., Guler, A. D., Gutmann, D. H., Halpern, C. H., Kucenas, S. C., Kushida, C. A., Lemieux, M., Liddelow, S., Macauley, S. L., Li, Q., Quinn, M. A., Roberts, L. W., Saligrama, N., Taylor, K. R., Venkatesh, H. S., Yalcin, B., Zuchero, J. B. 2020


    The COVID19 crisis has magnified the issues plaguing academic science, but it has also provided the scientific establishment with an unprecedented opportunity to reset. Shoring up the foundation of academic science will require a concerted effort between funding agencies, universities, and the public to rethink how we support scientists, with a special emphasis on early career researchers.

    View details for DOI 10.1016/j.cell.2020.05.045

    View details for PubMedID 32533917

  • Electrical and synaptic integration of glioma into neural circuits. Nature Venkatesh, H. S., Morishita, W., Geraghty, A. C., Silverbush, D., Gillespie, S. M., Arzt, M., Tam, L. T., Espenel, C., Ponnuswami, A., Ni, L., Woo, P. J., Taylor, K. R., Agarwal, A., Regev, A., Brang, D., Vogel, H., Hervey-Jumper, S., Bergles, D. E., Suva, M. L., Malenka, R. C., Monje, M. 2019


    High-grade gliomas are lethal brain cancers whose progression is robustly regulated by neuronal activity. Activity-regulated release of growth factors promotes glioma growth, but this alone is insufficient to explain the effect that neuronal activity exerts on glioma progression. Here we show that neuron and glioma interactions include electrochemical communication through bona fide AMPA receptor-dependent neuron-glioma synapses. Neuronal activity also evokes non-synaptic activity-dependent potassium currents that are amplified by gap junction-mediated tumour interconnections, forming an electrically coupled network. Depolarization of glioma membranes assessed by in vivo optogenetics promotes proliferation, whereas pharmacologically or genetically blocking electrochemical signalling inhibits the growth of glioma xenografts and extends mouse survival. Emphasizing the positive feedback mechanisms by which gliomas increase neuronal excitability and thus activity-regulated glioma growth, human intraoperative electrocorticography demonstrates increased cortical excitability in the glioma-infiltrated brain. Together, these findings indicate that synaptic and electrical integration into neural circuits promotes glioma progression.

    View details for DOI 10.1038/s41586-019-1563-y

    View details for PubMedID 31534222

  • ALK2 inhibitors display beneficial effects in preclinical models of ACVR1 mutant diffuse intrinsic pontine glioma. Communications biology Carvalho, D. n., Taylor, K. R., Olaciregui, N. G., Molinari, V. n., Clarke, M. n., Mackay, A. n., Ruddle, R. n., Henley, A. n., Valenti, M. n., Hayes, A. n., Brandon, A. D., Eccles, S. A., Raynaud, F. n., Boudhar, A. n., Monje, M. n., Popov, S. n., Moore, A. S., Mora, J. n., Cruz, O. n., Vinci, M. n., Brennan, P. E., Bullock, A. N., Carcaboso, A. M., Jones, C. n. 2019; 2 (1): 156


    Diffuse intrinsic pontine glioma (DIPG) is a lethal childhood brainstem tumour, with a quarter of patients harbouring somatic mutations in ACVR1, encoding the serine/threonine kinase ALK2. Despite being an amenable drug target, little has been done to-date to systematically evaluate the role of ACVR1 in DIPG, nor to screen currently available inhibitors in patient-derived tumour models. Here we show the dependence of DIPG cells on the mutant receptor, and the preclinical efficacy of two distinct chemotypes of ALK2 inhibitor in vitro and in vivo. We demonstrate the pyrazolo[1,5-a]pyrimidine LDN-193189 and the pyridine LDN-214117 to be orally bioavailable and well-tolerated, with good brain penetration. Treatment of immunodeprived mice bearing orthotopic xenografts of H3.3K27M, ACVR1R206H mutant HSJD-DIPG-007 cells with 25 mg/kg LDN-193189 or LDN-214117 for 28 days extended survival compared with vehicle controls. Development of ALK2 inhibitors with improved potency, selectivity and advantageous pharmacokinetic properties may play an important role in therapy for DIPG patients.

    View details for DOI 10.1038/s42003-019-0420-8

    View details for PubMedID 31925004

  • Functional diversity and cooperativity between subclonal populations of pediatric glioblastoma and diffuse intrinsic pontine glioma cells NATURE MEDICINE Vinci, M., Burford, A., Molinari, V., Kessler, K., Popov, S., Clarke, M., Taylor, K. R., Pemberton, H. N., Lord, C. J., Gutteridge, A., Forshew, T., Carvalho, D., Marshall, L., Qin, E. Y., Ingram, W. J., Moore, A. S., Ng, H., Trabelsi, S., Hmida-Ben Brahim, D., Entz-Werle, N., Zacharoulis, S., Vaidya, S., Mandeville, H. C., Bridges, L. R., Martin, A. J., Al-Sarraj, S., Chandler, C., Sunol, M., Mora, J., de Torres, C., Cruz, O., Carcaboso, A. M., Monje, M., Mackay, A., Jones, C. 2018; 24 (8): 1204-+


    The failure to develop effective therapies for pediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) is in part due to their intrinsic heterogeneity. We aimed to quantitatively assess the extent to which this was present in these tumors through subclonal genomic analyses and to determine whether distinct tumor subpopulations may interact to promote tumorigenesis by generating subclonal patient-derived models in vitro and in vivo. Analysis of 142 sequenced tumors revealed multiple tumor subclones, spatially and temporally coexisting in a stable manner as observed by multiple sampling strategies. We isolated genotypically and phenotypically distinct subpopulations that we propose cooperate to enhance tumorigenicity and resistance to therapy. Inactivating mutations in the H4K20 histone methyltransferase KMT5B (SUV420H1), present in <1% of cells, abrogate DNA repair and confer increased invasion and migration on neighboring cells, in vitro and in vivo, through chemokine signaling and modulation of integrins. These data indicate that even rare tumor subpopulations may exert profound effects on tumorigenesis as a whole and may represent a new avenue for therapeutic development. Unraveling the mechanisms of subclonal diversity and communication in pGBM and DIPG will be an important step toward overcoming barriers to effective treatments.

    View details for PubMedID 29967352

    View details for PubMedCentralID PMC6086334

  • DRUG SCREENING LINKED TO MOLECULAR PROFILING IDENTIFIES NOVEL DEPENDENCIES IN PATIENT-DERIVED PRIMARY CULTURES OF PAEDIATRIC HIGH GRADE GLIOMA AND DIPG Mackay, A., Molinari, V., Carvalho, D., Pemberton, H., Temelso, S., Burford, A., Clarke, M., Fofana, M., Boult, J., Izquierdo, E., Taylor, K., Bjerke, L., Salom, J., Kessler, K., Rogers, R., Chandler, C., Zebian, B., Martin, A., Stapleton, S., Hettige, S., Marshall, L., Carceller, F., Mandeville, H., Vaidya, S., Bridges, L., Al-Sarraj, S., Pears, J., Mastronuzzi, A., Carai, A., del Bufalo, F., de Torres, C., Sunol, M., Cruz, O., Mora, J., Moore, A., Robinson, S., Lord, C., Montero Carcaboso, A., Vinci, M., Jones, C. OXFORD UNIV PRESS INC. 2018: 93–94
  • Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma CANCER CELL Mackay, A., Burford, A., Carvalho, D., Izquierdo, E., Fazal-Salom, J., Taylor, K. R., Bjerke, L., Clarke, M., Vinci, M., Nandhabalan, M., Temelso, S., Popov, S., Molinari, V., Raman, P., Waanders, A. J., Han, H. J., Gupta, S., Marshall, L., Zacharoulis, S., Vaidya, S., Mandeville, H. C., Bridges, L. R., Martin, A. J., Al-Sarraj, S., Chandler, C., Ng, H., Li, X., Mu, K., Trabelsi, S., H'mida-Ben Brahim, D., Kisljakov, A. N., Konovalov, D. M., Moore, A. S., Montero Carcaboso, A., Sunol, M., de Torres, C., Cruz, O., Mora, J., Shats, L. I., Stavale, J. N., Bidinotto, L. T., Reis, R. M., Entz-Werle, N., Farrell, M., Cryan, J., Crimmins, D., Caird, J., Pears, J., Monje, M., Debily, M., Castel, D., Grill, J., Hawkins, C., Nikbakht, H., Jabado, N., Baker, S. J., Pfister, S. M., Jones, D. W., Fouladi, M., von Bueren, A. O., Baudis, M., Resnick, A., Jones, C. 2017; 32 (4): 520-+


    We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification.

    View details for PubMedID 28966033

    View details for PubMedCentralID PMC5637314

  • Transcriptional Dependencies in Diffuse Intrinsic Pontine Glioma CANCER CELL Nagaraja, S., Vitanza, N. A., Woo, P. J., Taylor, K. R., Liu, F., Zhang, L., Li, M., Meng, W., Ponnuswami, A., Sun, W., Ma, J., Hulleman, E., Swigut, T., Wysocka, J., Tang, Y., Monje, M. 2017; 31 (5): 635-?


    Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric cancer with limited therapeutic options. The majority of cases of DIPG exhibit a mutation in histone-3 (H3K27M) that results in oncogenic transcriptional aberrancies. We show here that DIPG is vulnerable to transcriptional disruption using bromodomain inhibition or CDK7 blockade. Targeting oncogenic transcription through either of these methods synergizes with HDAC inhibition, and DIPG cells resistant to HDAC inhibitor therapy retain sensitivity to CDK7 blockade. Identification of super-enhancers in DIPG provides insights toward the cell of origin, highlighting oligodendroglial lineage genes, and reveals unexpected mechanisms mediating tumor viability and invasion, including potassium channel function and EPH receptor signaling. The findings presented demonstrate transcriptional vulnerabilities and elucidate previously unknown mechanisms of DIPG pathobiology.

    View details for DOI 10.1016/j.ccell.2017.03.011

    View details for Web of Science ID 000400738600008

    View details for PubMedID 28434841

  • Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma NATURE GENETICS Taylor, K. R., Mackay, A., Truffaux, N., Butterfield, Y. S., Morozova, O., Philippe, C., Castel, D., Grasso, C. S., Vinci, M., Carvalho, D., Carcaboso, A. M., de Torres, C., Cruz, O., Mora, J., Entz-Werle, N., Ingram, W. J., Monje, M., Hargrave, D., Bullock, A. N., Puget, S., Yip, S., Jones, C., Grill, J. 2014; 46 (5): 457-461


    Diffuse intrinsic pontine gliomas (DIPGs) are highly infiltrative malignant glial neoplasms of the ventral pons that, due to their location within the brain, are unsuitable for surgical resection and consequently have a universally dismal clinical outcome. The median survival time is 9-12 months, with neither chemotherapeutic nor targeted agents showing substantial survival benefit in clinical trials in children with these tumors. We report the identification of recurrent activating mutations in the ACVR1 gene, which encodes a type I activin receptor serine/threonine kinase, in 21% of DIPG samples. Strikingly, these somatic mutations (encoding p.Arg206His, p.Arg258Gly, p.Gly328Glu, p.Gly328Val, p.Gly328Trp and p.Gly356Asp substitutions) have not been reported previously in cancer but are identical to mutations found in the germ line of individuals with the congenital childhood developmental disorder fibrodysplasia ossificans progressiva (FOP) and have been shown to constitutively activate the BMP-TGF-β signaling pathway. These mutations represent new targets for therapeutic intervention in this otherwise incurable disease.

    View details for DOI 10.1038/ng.2925

    View details for PubMedID 24705252

  • Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations Nature Genetics Buczkowicz, P. 2014: 451-56