Neurosurgery Research Programs and Laboratories

The Stanford Department of Neurosurgery supports over 30 active laboratories investigating everything from brain injury, deep brain stimulation, brain tumors, epilepsy, and stroke, to the effects of stress and aging on the nervous system. And, although our research themes vary from lab to lab, they are all focused on aspects of disease and injury that can be investigated at the bench – and they all have clear implications for practices in the clinic and operating room.

Our lab focuses on how inflammatory responses after brain injury may affect neurological recovery. We utilize translational approaches to understand molecular mechanisms underlying functional recovery. Molecular events are modified in mice using either transgenic models or novel small molecule compounds, and then we evaluate the effects on functional recovery as well as on cellular and molecular responses.

The Brain Interfacing Laboratory is interested in the applicability of brain-machine interfaces as a platform technology for a variety of brain-related medical conditions, particularly stroke and epilepsy. This research spans both preclinical models and human clinical studies.

Our primary research interest is to understand the molecular and cellular mechanisms of cell death in the CNS following acute injuries such as ischemia and trauma and chronic neurodegenerative diseases. We focus on the role of oxidative stress, mitochondrial dysfunction, DNA damage and repair, various gene expressions and various transcription factors in the pathogenesis of necrosis and/or apoptosis. The long-term goal of our research is to derive therapeutic strategies at the cellular and molecular level to ameliorate cell death in CNS injuries.

The Chang Lab develops and implements new technologies to improve the diagnosis and treatment of rare neurological conditions. We are focused on finding less invasive ways to diagnose disease and translating our discoveries in the lab to patient care. 

The long-term goal of the Lu Chen Lab is to understand the cellular and molecular mechanisms that underlie synapse function during behavior in the developing and mature brain, and how synapse function is altered during mental retardation. In this broad research area, we are specifically interested in the molecular underpinnings of activity-dependent regulation of synaptic strength, the role of postsynaptic protein translation in plastic changes of synaptic activity, and the impairment of synapses in autism spectrum disorders (e.g. Fragile X syndrome) that involves changes in postsynaptic protein translation and synaptic strength.

Dr. Chichilnisky is a systems neurobiologist who explores how the retina of the eye processes and transmits visual information to the brain. The goal of the Chichilnisky lab is to understand signaling by the retina, its impact on vision, and the implications for treating vision loss. 

The Clinical Neuro-Oncology Laboratory investigates the outcomes of patients affected with brain, skull base and spine tumors. The goal of the laboratory is to improve patients’ care and outcome by analyzing clinical data from thousands of patients treated at our institution, with surgery as well as with other innovative treatments, such as stereotactic radiosurgery (SRS), by Cyberknife. Retrospective analysis of large patient cohorts and of big-data databases allows re-defining the indications for treatment, refining the surgical technique and identifying new fields of application of minimally-invasive techniques. 

The Stanford Spine Artificial Intelligence Laboratory is a collaboration of Stanford neurosurgeons, radiologists, orthopedic surgeons and data scientists who share the goal of advancing the field of artificial intelligence to provide better surgical outcomes for spine patients. Our laboratory works closely with the Stanford Center for Artificial Intelligence in Medicine and Imaging, and studies the application of computer vision and deep learning to spinal imaging, in addition to the use of statistical and machine learning modelling techniques to predict surgical outcomes and cost.

Our laboratory connects electronic systems to the nervous system to restore health and function after spinal cord injury. People whose bladder is paralyzed often have difficulty with bladder emptying and with continence. We are developing a second generation neural prosthesis, or implanted electrical stimulator, to restore these functions and reduce urinary tract infection, stone formation and kidney damage, and reduce the costs of their health care. People whose legs are paralyzed develop severe osteoporosis that can cause pathological fractures and other complications. We are studying whether osteoporosis can be prevented or reversed by vigorous exercise produced by electrical stimulation of leg muscles while on a rowing machine, in collaboration with the University of Oxford.

Our laboratory’s goal is to dissect the functional organization of motor circuits, particularly cortico-thalamo-basal ganglia networks, using electrophysiology, 2-photon microscopy, optogenetics, and genetic tools.  Our long-term scientific goal is to construct functional circuit diagrams and establish causal relationships between activity in specific groups of neurons, circuit function, animal motor behavior and motor learning, and thereby to decipher how the basal ganglia process information and guide motor behavior. 

The Stanford Neurosurgical Training and Innovation Center, under the direction of Juan C. Fernandez-Miranda, MD, has a dual educational and research role aiming to improve surgical techniques and outcomes by mastering knowledge of relevant surgical neuroanatomy. 

The Gephart lab focuses on translational neuro-oncology research, combining basic neuroscience, genetics, and tumor biology, with an unique insight into the pressing clinical questions facing patients with brain tumors.  We focus on understanding the genetic and epigenetic mechanisms driving tumorigenesis in the central nervous system. Ultimately these insights will identify novel drug targets and improve diagnostic capacity. 

My research interest focuses on the blood-brain barrier (BBB). We aim to selectively open the blood-brain barrier to allow drugs and immunotherapy to reach brain tumors. Our laboratory is highly translational to treat pediatric brain tumors and functions to bridge the preclinical gap by improving our ability to get promising targeted therapy across the BBB.  The development of a cranial window technique for intravital microscopy has provided a major advance in the acquisition of live dynamic images of the brain microvasculature and its response to various techniques to open the BBB around tumors. We also use high resolution MRI to follow the BBB in vivo using dynamic contrast enhanced imaging.

My research focuses on understanding the genetic and environmental etiology of complex diseases (e.g. cancer and Alzheimer’s disease) and for evaluating effective screening strategies based on etiological understanding. The areas of my research interests include molecular epidemiology, statistical genetics, cancer screening, health policy modeling, and risk prediction modeling. I have developed various statistical methods that can be used for identifying genetic and environmental risk factors and interactions between these factors using genome-wide association studies data. 

The goal of the Neuro-Rehabilitation Lab is to improve the lives of those who suffer from injuries to the neuro-axis. Our lab is integrated with Defense and Veterans Brain Injury Center (DVBIC) and Department of Rehabilitation at the VA Palo Alto and therefore spans the entire neural axis; traumatic brain, spinal cord and visual injury. We access longitudinal and continuous epidemiologic data as primary tools to focus on relevant functional outcomes that help Veterans, military personnel and civilians reintegrate into society after acute injury. 

Our laboratory is interested in identifying structural points within brain circuitry from which epileptic seizures initiate or propagate, determining the microcircuit (cellular and synaptic) mechanisms that promote such seizures, and developing real time interventions that prevent seizure occurrence or spread.  We use in in vitro and in vivo electrophysiology and imaging, and complementary computational approaches to address these aims.

Our lab’s primary research interest is to understand how specific neuronal circuits are established. We use mouse genetics, combinatorial immunochemical labeling and high-resolution laser scanning microscopy to identify, manipulate, and quantitatively analyze synaptic contacts within the complex neuronal milieu of the spinal cord. We have recently expanded our focus to include the enteric nervous system, where we are using the tools and concepts learned from our research on spinal circuitry to explore the neuronal circuitry of the gut.

The Lee Lab uses interdisciplinary approaches from biology and engineering to analyze, debug, and manipulate systems-level brain circuits. We seek to understand the connectivity and function of these large-scale networks in order to drive the development of new therapies for neurological diseases. This research finds its basic building blocks in areas ranging from medical imaging and signal processing to genetics and molecular biology.

My laboratory studies the biology of brain tumors with the goal of developing novel therapeutics for the treatment of malignant brain tumors and translating that research into clinical trials. Currently we are studying a variety of different protein pathways that we hypothesize to be important players in glioblastoma formation and growth. 

Dr. Lim's lab is focused on understanding basic mechanisms of immunosuppression in GBM. We extensively study both the myeloid and lymphocyte compartments to examine key players in the adaptive process utilized by GBM to avoid immune surveillance and elimination. We are involved in a number of clinical trials examining combination checkpoint blockade as well as molecular biomarkers to predict better response to immunotherapy in patients with GBM.

The Stanford Neural Prosthetics Translational Laboratory (NPTL) conducts research aimed at developing clinically useful neural prostheses for people with paralysis. Our eventual goal is to extract signals recorded from surgically implanted brain electrodes to provide accurate, high-speed, and robust control of computer cursors and other assistive technologies such as robotic arms. Our current projects are focused on improving communication rates provided by neurally-directed computer cursor control; combining high degree-of-freedom control signals decoded from the brain with advances in robotics to control a robotic arm; and the development of wireless systems which will enable the next generation of neural prosthetic devices. We make extensive use of our close relationship with the Stanford  Neural Prosthetics Systems Laboratory (NPSL), allowing us to benefit from tools and technologies developed in NPSL's pre-clinical research.

The Owen Lab investigates how neuromodulation shapes activity within the cortex and basal ganglia in the healthy brain, and in neurological disease. Defects in these brain structures can lead to impulsive and compulsive behavior, and an inability to adapt to dynamically changing environments. These deficits can be debilitating in diseases such as Obsessive-Compulsive Disorder (OCD), Parkinson’s Disease, and Autism. Our goals are to understand how specialized cell types and signaling pathways interact during healthy physiological activity; to define how those interactions are affected in neurological disease; and to identify how these circuit elements can be more efficiently targeted for treatment in neurological disease. 

In adult human brain development, neurogenesis ceases at birth and the vast majority of areas in the adult mammalian brain no longer produce new neurons, even in the face of debilitating injury or disease. However, there are distinct exceptions to the rule. In rodents and humans, the hippocampus is one of the few areas where neurogenesis continues through adult life. Among other roles, the hippocampus is most well known as the area of the brain that mediates short-term learning and memory. Hippocampal function is affected in many diseases with grave human consequences. The two most common presentations of this dysfunction are memory deficits that accompany Alzheimer's disease and major depressive disorders. The fact that the addition/replacement of neurons uniquely occurs in the hippocampus suggests that neurogenesis itself plays a useful role within a pre-existing neural network. However, the mechanisms that regulate this process are not understood. Our research examines regions of adult brain where neurogenesis occurs to understand how the brain regulates and utilizes this ability to add or replace neurons.

The Stanford University Medical Center (SUMC) Neurosurgery Spine Laboratory studies the clinical outcomes and biomechanical properties of various dynamic stabilization devices to improve upon the traditional rigid devices currently in use. We analyze the biomechanical properties of these devices using human cadavers and our Material Testing System (MTS, Eden Prairie, Minnesota) along with a pressure transducer/strain scanner. Using these instruments, we study the intradiscal pressures (IDPs) at the level of the semi-rigid fusions, as well as the effects of the fusions on adjacent segment IDPs; the results have been favorable when compared with traditional rigid devices.

In addition to studying the clinical and biomechanical evaluations of semi-rigid stabilization systems, we are investigating the biomechanical properties of various artificial discs placed into human cadaveric spines. The MTS system has also been used for these studies. We have also begun preliminary research with human disc cells. Human disc cells are grown in cell culture with the goal of creating replacement discs formulated from the patient's own disc material. This type of disc may be superior to the artificial discs currently being used.

Claudia K. Petritsch

Brain tumor laboratory models

There are over 200 diverse histological diagnoses of brain tumors, many of which are rare and challenging to treat. The Petritsch lab conducts basic and preclinical research aimed at unraveling the underlying causes for this heterogeneity and ultimately improving therapies for patients with brain tumors. Of special emphasis, we investigate glial cells as a potential cellular origin of glioma, a common brain tumor. 

Pediatric high-grade gliomas are invasive and poised to recur after surgical resection. The Prolo Lab uses new advances in genetic and epigenetic tools to understand what molecular pathways drive tumor cell invasion, and how these pathways can be targeted for novel treatments. 

The Sapolsky lab has worked in three general areas:  a) the ability of stress and stress hormones, such as glucocorticoids, to damage the nervous system, accelerating aspects of brain aging and making neurons more vulnerable to necrotic neurological insults;  b) the design of gene therapy strategies to protect neurons from both the adverse effects of stress, and from necrotic insults;  c) the ability of the protozoan parasite Toxoplasma gondii to enter the nervous system and alter a variety of aspects of brain function and behavior.

The ultimate goal of my laboratory and research is to rapidly advance our understanding of normal brain function at the molecular, cellular, circuit, behavioral and functional levels, and to elucidate the pathological process underlying malfunction of the nervous system following injury and neurologic disorders such as stroke, Alzheimer’s disease and autism. Our fundamental goal is to improve the quality of life for patients with brain disorders. We are aiming to probe and understand the process leading to the functional and behavioral malfunction in these disorders focusing on a set of target genes/proteins which we have discovered to be regulated in brain in the context of these disorders. 

My research focuses on screening strategies to identify and characterize cancer stem cells (CSCs) in human gliomas. We are pursuing this in several ways: 1) a novel colony-forming antibody live cell array to identify distinct CSC surface phenotypes, 2) RNAi screens to identify kinases critical for CSC tumorigenicity, 3) high throughput small molecule and chemical screens to identify compounds that selectively kill or target CSCs, and 4) identifying CSCs using the tumor specific EGFRvIII.

Our laboratory focuses on the organizational principles neuronal microcircuits, mechanisms of brain rhythms, cannabinoid signaling and the mechanistic bases of circuit dysfunction in epilepsy. We employ closely integrated experimental and theoretical techniques, including the selective modulation of different cell types in various parts of the brain to block seizures in an on-demand manner and ameliorate epilepsy-related cognitive deficits. A major effort in the lab is aimed at constructing highly realistic full-scale models of neuronal circuits in seizure-prone areas of the brain in order to simulate the emergence of normal and epileptic activity patterns with unprecedented biological realism using powerful supercomputers.

Our research group explores using administrative databases to improve patient outcomes in spine surgery procedures.  Presently the group is working on a prospective measure to assess the risk of complications in spine surgery procedures. I am studying the impact of patient disease process, choice of operative approach, and patient pre-operative comorbidities on complication occurrence. Collaborating with the Biostatistics and Health Research and Policy departments at Stanford, we are developing statistical models that may be used to predict adverse event occurrence and to assist in relative risk modelling.

The goal of this effort will be to develop a clinical tool that may be used to assess pre-operatively the risk of peri-operative adverse events given patient-, condition- and approach-related variables. This will contribute to patient counseling and may inform post-operative care in at risk patients.

The Stanford Artificial Retina Project is developing an implantable device to provide artificial vision to patients blinded by retinal degeneration. The interdisciplinary team, led by E.J. Chichilnisky in the Neurosurgery Department, is designing the hardware, surgery, and neuroscience-based algorithms that will produce a revolutionary device that can correctly interact with neural circuits to produce high-fidelity artificial vision.

The Stanford Partnership for Spinal Cord Injury and Repair (SP-SCIR) is a consortium between members of the Department of Neurosurgery and the Spinal Cord Injury Units at the VA Palo Alto Health Care System and the Santa Clara Valley Medical Center.  It aims to restore function after spinal cord injury by investigating the mechanisms underlying a traumatic spinal cord injury, developing novel methods of repair and regeneration, and maximizing quality of life with bioengineering and technology such as neural prostheses. Internal research collaborators include the Departments of Anesthesiology, Chemical and Systems Biology, Comparative Biology, Electrical Engineering, Materials Science and Engineering, Neurology and Neurological Sciences, and Orthopaedic Surgery. External research collaborators include the University of California San Francisco, Case Western Reserve University, the University and Federal Institute of Technology (ETH) Zurich, the Universities of Oxford and Cambridge, Harvard University, University of California Irvine and University of Western Australia.

Stanford Neuromolecular Innovation Program (SNIP) is an interdisciplinary research initiative that brings together clinical experts in Neurosurgery and Neurology with leading basic scientists in the fields of Genetics, Biochemistry and Bioengineering. SNIP’s goal is to develop and implement new technologies to improve the diagnosis and treatment of patients affected by neurological conditions. Fundamentally, SNIP strives to provide better and more effective patient care.

Our laboratory investigates the pathophysiology of cerebral ischemia, develops neuroprotective agents, and employs novel approaches such as stem cell transplantation and optogenetic stimulation to enhance post-stroke functional recovery. Our clinical research investigates innovative surgical, endovascular and radiosurgical approaches for treating patients with difficult intracranial aneurysms, complex vascular malformations and occlusive cerebrovascular disease, including Moyamoya.

Thomas Südhof is interested in how synapses form and function in the developing and adult brain. His work focuses on the role of synaptic cell-adhesion molecules in establishing synapses and shaping their properties, on pre- and postsynaptic mechanisms of membrane traffic, and on impairments in synapse formation and synaptic function in neuropsychiatric and neurodegenerative disorders. To address these questions, Südhof's laboratory employs a spectrum of approaches ranging from biophysical studies and physiological and behavioral investigations of mutant mice to analyses of human neurons.

Our lab develops non-invasive and invasive neuromodulation techniques for the treatment of diseases like Parkinson’s, functional impairment following stroke and tinnitus. Our stimulation algorithms can be applied by means of different stimulation modalities: electrical pulses delivered through surgically implanted electrodes, mild vibratory stimuli administered to the finger tips and gentle sound stimuli administered using standard stereo headsets. Our technology appears to induce long-lasting relief with stimulation that is only delivered for a few hours on an intermittent or regular basis. Our research is based on brain plasticity principles and dynamic self-organization. We use comprehensive computational neuroscience methods derived from non-linear dynamics, statistical physics, and numerics as well as high performance computing. We are engaged in pre-clinical studies, perform electrophysiological recordings as well as clinical studies.

The long-term goal of the research in my lab is to discover treatments to restore function following spinal cord injury, either by manipulation of transplanted stem cells or by activation of endogenous progenitors. Corticospinal motor neurons are the brain neurons that control the most precise aspects of voluntary movement. They send long axons down the spinal cord, and injury to these cells is central to paralysis in spinal cord injury. Future regeneration strategies are limited by the current understanding of the development of corticospinal motor neurons from stem cells, as well as of the response of these neurons to spinal cord injury. Understanding at the molecular level how corticospinal motor neurons normally develop, and how they respond to spinal cord injury, will enable enhancement of regeneration, either via transplantation of cells such as induced pluripotent stem (iPS) cells or by activation of endogenous stem or progenitor cells.

Our laboratory is particularly interested in microRNAs—small non-coding RNAs that simultaneously regulate the expression of multiple genes— and seeks to identify microRNA controls both over corticospinal motor neuron development and over these cells’ response to spinal cord injury. We have identified several microRNAs that appear to be differentially expressed during corticospinal motor neuron development, and may play a central role in this process. We are testing the ability of these microRNAs to alter the fate of progenitor or stem cells and turn them into corticospinal motor neurons. Building upon those developmentally regulated microRNAs, we are also investigating their specific roles in spinal cord injury, and their possible roles in recovery.

The focus of the Stanford Neurosurgical Artificial Intelligence and Machine Learning laboratory is to utilize precision medicine techniques to improve the diagnosis and treatment of neurologic conditions. From traumatic brain injury to spinal scoliosis, the ability to capture detailed data regarding clinical symptoms and treatment outcomes has empowered us to do better for patients. Utilize data to do better for patients, that’s what we do.

Mitochondria move and undergo fission and fusion in all eukaryotic cells. The accurate allocation of mitochondria in neurons is particularly critical due to the significance of mitochondria for ATP supply, Ca++ homeostasis and apoptosis and the importance of these functions to the distal extremities of neurons. In addition, defective mitochondria, which can be highly deleterious to a cell because of their output of reactive oxygen species, need to be repaired by fusing with healthy mitochondria or cleared from the cell. Thus mitochondrial cell biology poses critical questions for all cells, but especially for neurons: how the cell sets up an adequate distribution of the organelle; how it sustains mitochondria in the periphery; and how mitochondria are removed after damage. The goal of our research is to understand the regulatory mechanisms controlling mitochondrial dynamics and function and the mechanisms by which even subtle perturbations of these processes may contribute to neurodegenerative disorders.

The goal of this laboratory is to define targets for cancer therapeutics by identifying alterations in signal transduction proteins and then translate these findings into important clinical tools, including one of the first effective peptide vaccines against cancer. The major type of cancer that we study is glioblastoma multiforme, the most common and devastating of the human brain tumors, but this work has also had implications for lung, breast, ovarian and prostate cancers.

Glia represent more than half of the cells in the human brain, yet compared to neurons much less is known about their important roles in brain development, function, and disease. Our lab aims to use cutting-edge cell biology techniques to uncover the cellular mechanisms by which glia sculpt and regulate the nervous system. We are particularly interested in understanding how glia form the insulating myelin sheath, and why regeneration of lost myelin fails in diseases like multiple sclerosis and after stroke. In the long term we aim to explore glia as untapped therapeutic targets for diverse diseases of the nervous system.