Bio

Clinical Focus


  • Neuro Oncology
  • Neurology

Academic Appointments


Honors & Awards


  • New Faculty Physician Scientist Translational Research Award, California Institute of Regenerative Medicine (CIRM) (2013 - 2018)
  • Basic Science IV Award, California Institute of Regenerative Medicine (CIRM) (2012 - 2015)
  • ‘A’ Award, Alex’s Lemonade Stand Foundation (2012-2015)
  • Peter A. Steck Memorial Award, Pediatric Brain Tumor Foundation (2011)
  • K08 Mentored Clinical Scientist Career Development Award, National Institutes of Neurological Disorders and Stroke (2010 - 2015)
  • Young Investigator Award, Hagerty Foundation for Glioma Research (2006)

Boards, Advisory Committees, Professional Organizations


  • Chair, Brainstem Glioma Working Group, Pediatric Brain Tumor Consortium (2013 - Present)
  • Member, Pediatric Brain Tumor Consortium Translational Biology Committee (2012 - Present)
  • Institutional Co-PI, Pediatric Brain Tumor Consortium (PBTC) (2012 - Present)
  • Member, Children’s Oncology Group (COG) (2011 - Present)

Professional Education


  • Fellowship:Stanford University - Dept of Neurology (06/30/2010) CA
  • Residency:Brigham and Women's Hospital Harvard Medical School (06/30/2008) MA
  • Internship:Stanford University (06/30/2005) CA
  • Medical Education:Stanford University (06/13/2004) CA
  • Residency:Massachusetts General Hospital (06/30/2008) MA
  • Board Certification: Neurology, American Board of Psychiatry and Neurology (2008)
  • PhD, Stanford University, Neuroscience (2004)
  • MD, Stanford University (2004)

Research & Scholarship

Current Research and Scholarly Interests


Much of brain development occurs after birth. Maturation of complex neural circuitry necessary for high-level cognitive and motor functions occurs throughout childhood and young adulthood. Central to the process of developing or strengthening a functional neural circuit is the generation of new glial cells for neuronal support, synapse formation and myelination. In some brain regions, such as the hippocampus, new neuron production occurs throughout postnatal life and is believed to subserve normal memory function.

The Monje Lab studies the molecular and cellular mechanisms of postnatal neurodevelopment. This includes microenvironmental influences on neural precursor cell fate choice in normal neurodevelopment and in disease states. Areas of emphasis include neuronal instruction of gliogenesis, cellular contributions to the neurogenic and gliogenic signaling microenvironment, molecular determinants of neural precursor cell fate, and the role of neural precursor cells in oncogenesis and repair mechanisms. As a practicing neurologist and Neuro-oncologist, Dr Monje is particularly interested in the roles for neural precursor cell function and dysfunction in the origins of pediatric brain tumors and the consequences of cancer treatment. As a paradigm of pediatric gliogenesis, we have been focusing on brainstem tumors, whose spatial and temporal specificity bespeak an underlying developmental cause.

Clinical Trials


  • Phase I Rindopepimut After Conventional Radiation in Children w/ Diffuse Intrinsic Pontine Gliomas Not Recruiting

    This is a research study of patients with diffuse intrinsic pontine gliomas. We hope to learn about the safety and efficacy of treating pediatric diffuse intrinsic pontine glioma patients with the EGFRvIII peptide vaccine after conventional radiation.

    Stanford is currently not accepting patients for this trial. For more information, please contact Christina Huang, 650-723-0574.

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  • Bevacizumab and Lapatinib in Children With Recurrent or Refractory Ependymoma Not Recruiting

    The goal of this clinical research study is to learn if the combination of Avastin (bevacizumab) and Tykerb (lapatinib) can help to control ependymoma in pediatric patients. The safety of this drug combination will also be studied.

    Stanford is currently not accepting patients for this trial. For more information, please contact Carissa Bailey, (650) 725 - 4708.

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  • Methylphenidate HCl or Modafinil in Treating Young Patients With Excessive Daytime Sleepiness After Cancer Therapy Not Recruiting

    RATIONALE: Methylphenidate hydrochloride or modafinil may help reduce daytime sleepiness and improve the quality of life of patients with excessive daytime sleepiness after cancer therapy. It is not yet known whether methylphenidate hydrochloride or modafinil are more effective than a placebo in reducing daytime sleepiness in these patients. PURPOSE: This randomized phase II trial is studying methylphenidate hydrochloride or modafinil to see how well they work compared with a placebo in treating young patients with excessive daytime sleepiness after cancer therapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • Vismodegib in Treating Younger Patients With Recurrent or Refractory Medulloblastoma Not Recruiting

    This phase II trial studies how well vismodegib works in treating younger patients with recurrent or refractory medulloblastoma. Vismodegib may slow the growth of tumor cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Christina Huang, 650-723-0574.

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  • Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma Recruiting

    This phase I/II trial studies the side effects and the best dose of selumetinib and how well it works in treating young patients with recurrent or refractory low grade glioma. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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  • Chemotherapy Followed by Radiation Therapy in Treating Younger Patients With Newly Diagnosed Localized Central Nervous System Germ Cell Tumors Recruiting

    Drugs used as chemotherapy, such as carboplatin, etoposide, and ifosfamide work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x rays to kill tumor cells. Giving chemotherapy with radiation therapy may kill more tumor cells. This phase II trial studies how well chemotherapy and radiation therapy work in treating younger patients with newly diagnosed central nervous system germ cell tumors.

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Publications

Journal Articles


  • Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Monje, M., Mitra, S. S., Freret, M. E., Raveh, T. B., Kim, J., Masek, M., Attema, J. L., Li, G., Haddix, T., Edwards, M. S., Fisher, P. G., Weissman, I. L., Rowitch, D. H., Vogel, H., Wong, A. J., Beachy, P. A. 2011; 108 (11): 4453-4458

    Abstract

    Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive tumors of childhood that are almost universally fatal. Our understanding of this devastating cancer is limited by a dearth of available tissue for study and by the lack of a faithful animal model. Intriguingly, DIPGs are restricted to the ventral pons and occur during a narrow window of middle childhood, suggesting dysregulation of a postnatal neurodevelopmental process. Here, we report the identification of a previously undescribed population of immunophenotypic neural precursor cells in the human and murine brainstem whose temporal and spatial distributions correlate closely with the incidence of DIPG and highlight a candidate cell of origin. Using early postmortem DIPG tumor tissue, we have established in vitro and xenograft models and find that the Hedgehog (Hh) signaling pathway implicated in many developmental and oncogenic processes is active in DIPG tumor cells. Modulation of Hh pathway activity has functional consequences for DIPG self-renewal capacity in neurosphere culture. The Hh pathway also appears to be active in normal ventral pontine precursor-like cells of the mouse, and unregulated pathway activity results in hypertrophy of the ventral pons. Together, these findings provide a foundation for understanding the cellular and molecular origins of DIPG, and suggest that the Hh pathway represents a potential therapeutic target in this devastating pediatric tumor.

    View details for DOI 10.1073/pnas.1101657108

    View details for Web of Science ID 000288450900040

    View details for PubMedID 21368213

  • Impaired human hippocampal neurogenesis after treatment for central nervous system ANNALS OF NEUROLOGY Monje, M. L., Vogel, H., Masek, M., Ligon, K. L., Fisher, P. G., Palmer, T. D. 2007; 62 (5): 515-520

    Abstract

    The effects of cancer treatments such as cranial radiation and chemotherapy on human hippocampal neurogenesis remain unknown. In this study, we examine neuropathological markers of neurogenesis and inflammation in the human hippocampus after treatment for acute myelogenous leukemia or medulloblastoma. We demonstrate a persistent radiation-induced microglial inflammation that is accompanied by nearly complete inhibition of neurogenesis after cancer treatment. These findings are consistent with preclinical animal studies and suggest potential therapeutic strategies.

    View details for DOI 10.1002/ana.21214

    View details for Web of Science ID 000251383300012

    View details for PubMedID 17786983

  • Inflammatory blockade restores adult hippocampal neurogenesis SCIENCE Monje, M. L., Toda, H., Palmer, T. D. 2003; 302 (5651): 1760-1765

    Abstract

    Cranial radiation therapy causes a progressive decline in cognitive function that is linked to impaired neurogenesis. Chronic inflammation accompanies radiation injury, suggesting that inflammatory processes may contribute to neural stem cell dysfunction. Here, we show that neuroinflammation alone inhibits neurogenesis and that inflammatory blockade with indomethacin, a common nonsteroidal anti-inflammatory drug, restores neurogenesis after endotoxin-induced inflammation and augments neurogenesis after cranial irradiation.

    View details for Web of Science ID 000186970100047

    View details for PubMedID 14615545

  • Irradiation induces neural precursor-cell dysfunction NATURE MEDICINE Monje, M. L., Mizumatsu, S., Fike, J. R., Palmer, T. D. 2002; 8 (9): 955-962

    Abstract

    In both pediatric and adult patients, cranial radiation therapy causes a debilitating cognitive decline that is poorly understood and currently untreatable. This decline is characterized by hippocampal dysfunction, and seems to involve a radiation-induced decrease in postnatal hippocampal neurogenesis. Here we show that the deficit in neurogenesis reflects alterations in the microenvironment that regulates progenitor-cell fate, as well as a defect in the proliferative capacity of the neural progenitor-cell population. Not only is hippocampal neurogenesis ablated, but the remaining neural precursors adopt glial fates and transplants of non-irradiated neural precursor cells fail to differentiate into neurons in the irradiated hippocampus. The inhibition of neurogenesis is accompanied by marked alterations in the neurogenic microenvironment, including disruption of the microvascular angiogenesis associated with adult neurogenesis and a marked increase in the number and activation status of microglia within the neurogenic zone. These findings provide clear targets for future therapeutic interventions.

    View details for DOI 10.1038/nm749

    View details for Web of Science ID 000177757900030

    View details for PubMedID 12161748

  • Functional and structural differences in the hippocampus associated with memory deficits in adult survivors of acute lymphoblastic leukemia PEDIATRIC BLOOD & CANCER Monje, M., Thomason, M. E., Rigolo, L., Wang, Y., Waber, D. P., Sallan, S. E., Golby, A. J. 2013; 60 (2): 293-300

    Abstract

    Radiation and chemotherapy targeted to the central nervous system (CNS) can cause cognitive impairment, including impaired memory. These memory impairments may be referable to damage to hippocampal structures resulting from CNS treatment.In the present study, we explored episodic memory and its neuroimaging correlates in 10 adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with cranial radiation therapy and both systemic and intrathecal chemotherapy and 10 controls matched for age and sex, using a subsequent memory paradigm after episodic encoding of visual scenes.We report behavioral, structural, and functional changes in the brains of the adult survivors. They demonstrated poorer recognition memory, hippocampal atrophy, and altered blood oxygenation level-dependent (BOLD) signal in the hippocampus. Whole brain statistical map analysis revealed increased BOLD signal/activation in several brain regions during unsuccessful encoding in ALL survivors, potentially reflecting ineffective neural recruitment. Individual differences in memory performance in ALL participants were related to magnitude of BOLD response in regions associated with successful encoding.Taken together, these findings describe long term neuroimaging correlates of cognitive dysfunction after childhood exposure to CNS-targeted cancer therapies, suggesting enduring damage to episodic memory systems.

    View details for DOI 10.1002/pbc.24263

    View details for Web of Science ID 000312557600021

    View details for PubMedID 22887801

  • Effect of cancer therapy on neural stem cells: implications for cognitive function CURRENT OPINION IN ONCOLOGY Gibson, E., Monje, M. 2012; 24 (6): 672-678

    Abstract

    Modern cancer therapies have allowed for a dramatic increase in the survival rates in both children and adults. However, a frequent and unfortunate side-effect of cancer therapy is a long-term decline in neurocognitive function. Specifically, cranial radiation therapy markedly alters memory processes, while chemotherapeutic agents are correlated with deficits in attention, concentration, and speed of information processing. Here, we describe the putative cellular etiologies of cancer treatment-induced cognitive decline, with an emphasis on the role of neural stem and precursor cell dysfunction.New studies highlight the lasting effects of chemotherapy on memory, executive function, attention, and speed of information processing up to 20 years following chemotherapy. Cognitive decrements are associated with decreased white-matter integrity as well as alterations in stem cell function in humans and rodent models of cancer therapy. Genetic polymorphisms may underlie differential sensitivity of certain individuals to the neurological consequences of chemotherapy. Increasing data support the concept that disruption of normal neural stem and precursor cell function is an important causative factor for the cognitive deficits that result from cancer therapy in both children and adults.Further studies are needed to elucidate the role of chemotherapy on cell-intrinsic processes and cellular microenvironments. Further, the effects of the new generation of targeted molecular therapies on neural stem and progenitor cell function remains largely untested. Understanding the mechanisms behind cancer therapy-induced damage to neural stem and precursor cell populations will elucidate neuroprotective and cell replacement strategies aimed at preserving cognition after cancer therapy.

    View details for DOI 10.1097/CCO.0b013e3283571a8e

    View details for Web of Science ID 000310361500011

    View details for PubMedID 22913969

  • Cognitive side effects of cancer therapy demonstrate a functional role for adult neurogenesis BEHAVIOURAL BRAIN RESEARCH Monje, M., Dietrich, J. 2012; 227 (2): 376-379

    Abstract

    Cancer therapies frequently result in a spectrum of neurocognitive deficits that include impaired learning, memory, attention and speed of information processing. Damage to dynamic neural progenitor cell populations in the brain are emerging as important etiologic factors. Radiation and chemotherapy-induced damage to neural progenitor populations responsible for adult hippocampal neurogenesis and for maintenance of subcortical white matter integrity are now believed to play major roles in the neurocognitive impairment many cancer survivors experience.

    View details for DOI 10.1016/j.bbr.2011.05.012

    View details for Web of Science ID 000301404000010

    View details for PubMedID 21621557

  • Hedgehogs, Flies, Wnts and MYCs: The Time Has Come for Many Things in Medulloblastoma JOURNAL OF CLINICAL ONCOLOGY Monje, M., Beachy, P. A., Fisher, P. G. 2011; 29 (11): 1395-1398

    View details for DOI 10.1200/JCO.2010.34.0547

    View details for Web of Science ID 000289276900016

    View details for PubMedID 21357776

  • Neurological complications following treatment of children with brain tumors. Journal of pediatric rehabilitation medicine Monje, M., Fisher, P. G. 2011; 4 (1): 31-36

    Abstract

    Brain tumors and their treatments in children result in a range of neurological complications that can affect daily function and rehabilitation potential, including neurocognitive sequelae, ototoxicity, seizure disorders, stroke, and peripheral neuropathy. Deficits in cognitive function, particularly learning and memory, attention and speed of information processing, can be debilitating. With new insights to the cellular and molecular etiology of these deficits, new therapies for cognitive decline after therapy are emerging. Management strategies for other neurological complications are also emerging.

    View details for DOI 10.3233/PRM-2011-0150

    View details for PubMedID 21757808

  • Clinical Patterns and Biological Correlates of Cognitive Dysfunction Associated with Cancer Therapy ONCOLOGIST Dietrich, J., Monje, M., Wefel, J., Meyers, C. 2008; 13 (12): 1285-1295

    Abstract

    Standard oncological therapies, such as chemotherapy and cranial radiotherapy, frequently result in a spectrum of neurocognitive deficits that includes impaired learning, memory, attention, and speed of information processing. In addition to classical mechanisms of neurotoxicity associated with chemo- and radiotherapy, such as radiation necrosis and leukoencephalopathy, damage to dynamic progenitor cell populations in the brain is emerging as an important etiologic factor. Radiation- and chemotherapy-induced damage to progenitor populations responsible for maintenance of white matter integrity and adult hippocampal neurogenesis is now believed to play a major role in the neurocognitive impairment many cancer survivors experience.

    View details for DOI 10.1634/theoncologist.2008-0130

    View details for Web of Science ID 000261996600008

    View details for PubMedID 19019972

  • CRANIAL RADIATION THERAPY AND DAMAGE TO HIPPOCAMPAL NEUROGENESIS DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS Monje, M. 2008; 14 (3): 238-242

    Abstract

    Cranial radiation therapy is associated with a progressive decline in cognitive function, prominently memory function. Impairment of hippocampal neurogenesis is thought to be an important mechanism underlying this cognitive decline. Recent work has elucidated the mechanisms of radiation-induced failure of neurogenesis. Potential therapeutic interventions are emerging.

    View details for DOI 10.1002/ddrr.26

    View details for Web of Science ID 000262726500008

    View details for PubMedID 18924155

  • Excitation-neurogenesis coupling in adult neural stem/progenitor cells NEURON Deisseroth, K., Singla, S., Toda, H., Monje, M., Palmer, T. D., Malenka, R. C. 2004; 42 (4): 535-552

    Abstract

    A wide variety of in vivo manipulations influence neurogenesis in the adult hippocampus. It is not known, however, if adult neural stem/progenitor cells (NPCs) can intrinsically sense excitatory neural activity and thereby implement a direct coupling between excitation and neurogenesis. Moreover, the theoretical significance of activity-dependent neurogenesis in hippocampal-type memory processing networks has not been explored. Here we demonstrate that excitatory stimuli act directly on adult hippocampal NPCs to favor neuron production. The excitation is sensed via Ca(v)1.2/1.3 (L-type) Ca(2+) channels and NMDA receptors on the proliferating precursors. Excitation through this pathway acts to inhibit expression of the glial fate genes Hes1 and Id2 and increase expression of NeuroD, a positive regulator of neuronal differentiation. These activity-sensing properties of the adult NPCs, when applied as an "excitation-neurogenesis coupling rule" within a Hebbian neural network, predict significant advantages for both the temporary storage and the clearance of memories.

    View details for Web of Science ID 000221708300006

    View details for PubMedID 15157417

  • Radiation injury and neurogenesis CURRENT OPINION IN NEUROLOGY Monje, M. L., Palmer, T. 2003; 16 (2): 129-134

    Abstract

    For many cancers, survival depends on aggressive combined therapies, but treatment comes at a price. Children and adults who receive radiotherapy involving the brain frequently experience a progressive cognitive decline. The overt pathologies of radiation injury such as white matter necrosis or vasculopathy are the obvious "smoking guns" of dysfunction. However, many patients exhibit severe learning and memory deficits with no overt pathologic changes. This is especially true when the radiation field involves the temporal lobes. The cause of this debilitating dysfunction is currently unknown and untreatable.Within the temporal lobe, the hippocampal formation plays a central role in short-term learning and memory--the functions most notably affected by radiation. Recent work has also shown that hippocampus-dependent learning and memory are strongly influenced by the activity of neural stem cells and their proliferative progeny. The hippocampal granule cell layer undergoes continuous renewal and restructuring by the addition of new neurons. Radiation at much lower doses than that needed to injure the more resistant post-mitotic neurons and glia of the brain has been found to affect these highly proliferative progenitors severely. The stem/progenitor cell is so sensitive to radiation that a single low dose to the cranium of a mature rat is sufficient to ablate hippocampal neurogenesis.Progressive learning and memory deficits following irradiation may be caused by the accumulating hippocampal dysfunction that results from a long-term absence of normal stem/progenitor activity. Here, the authors describe the nature of this stem cell dysfunction and contemplate how restoration of stem/progenitor cell activity might be approached in experimental models and, eventually, the clinic.

    View details for DOI 10.1097/01.wco.0000063772.8181.b7

    View details for Web of Science ID 000182542200002

    View details for PubMedID 12644738

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