Dr. Rona Giffard’s laboratory studies stroke, a devastating problem that is the leading cause of long-term neurological disability and the third leading cause of death worldwide. The lab tries to identify ways to reduce ischemic brain injury, and to better understand the interactions between different brain cell types during injury and recovery. Astrocytes and their response to injury are an important focus in the lab. One significant finding has been that astrocyte impairment contributes to neuronal injury in global ischemia. Targeting protective strategies to astrocytes leads to markedly increased neuronal survival. 

Other areas of focus in the lab are:

• the increase in neurogenesis following stroke, and the deleterious effects of inflammation on neurogenesis in this setting
• ways to improve mitochondrial function to increase newborn neuron survival and modulate inflammation
• IL4 as a protective factor against stroke injury in male mice
• how biological sex differences impact the age at stroke and the outcome of stroke in humans sex differences in response to stroke, with a focus on differences in inflammation
• microRNAs that regulate important survival proteins, including members of the Bcl-2 family and heat shock proteins

Studies are performed in animal models and primary cultures from brain.

Principal Faculty: Rona Giffard M.D., PhD.

Historically, pain has been considered in relation to its etiologic or disease factors, such as the relationship between surgery and postoperative pain, herpes zoster and postherpetic neuralgia, and arthritis and painful joints. This has had the effect of addressing pain as a symptom of disease, and although much progress has been made in understanding the molecular and cellular mechanisms of disease, the resulting pain has not necessarily been alleviated. What is required, and has been missing from the evaluation, is an understanding of the underlying mechanisms responsible for the pain itself.

Dr. Mackey’s Stanford Systems Neuroscience and Pain Lab (SNAPL) is focused on elucidating and characterizing underlying mechanisms of pain and analgesia. Important mechanisms of nociception exist at the level of the gene through the neuron; however, pain is ultimately a subjective experience that does not commonly correspond to the level of tissue injury or nociception that a person experiences. Additionally, while much has been learned from animal models of pain, it is ultimately the human patient that needs to be studied to best understand and treat this terrible condition.

SNAPL uses a combination of sophisticated neurobehavioral, psychophysical and neuroimaging (fMRI, VBM, DTI, effective connectivity) techniques to investigate acute and chronic pain mechanisms and analgesia in the spinal cord and brain in humans. Dr. Mackey has several ongoing NIH, foundation and industry-funded projects related to:

• real-time fMRI and learned brain control
• cognitive and affective dimensions of pain
• pharmacologic fMRI
• spinal cord mapping
• epidemiology of chronic pain
• sodium channel blockers in neuropathic pain
• neurotoxins in neuropathic pain

Research fellowship opportunities are available for qualified candidates. These include immediate openings in MRI research and cognitive neuroscience, as well as an ongoing multi-departmental collaboration in Pain and/or Substance Use Disorders. To learn more, please see http://snapl.stanford.edu/postdoc/.

Principal Faculty: Sean Mackey M.D., PhD.

The Patient Safety Center of Inquiry at the VA Palo Alto Health Care System has 7 major areas of study and fellows participate in all aspects of laboratory activity and are expected to develop their own area of expertise under faculty guidance. The major areas of study include:

• Simulation-based training in decision making, crisis management, and teamwork
• Theory of organizational safety applied to health care
• Effects of sleep deprivation and fatigue on patient safety
• Cultures of safety in health care
• Safety-related event reporting and analysis
• Safety of human subjects in research
• and human factors issues in medical equipment design and use

In addition to its internal collaborators within the VA Palo Alto HCS and Veterans Health Administration (VHA), external collaborators include: The Center for Health Policy at Stanford University, the California Collaboration for Improving Patient Safety, and investigators from The Haas School of Business at UC Berkeley and from the Naval Postgraduate School in Monterey, CA.

Principal Faculty: David Gaba, MD, Steven Howard, MD, Kyle Harrison, MD.

The Clark laboratory pursues research questions in 2 areas related to pain management. The first focus of interest is on the mechanisms responsible for maladaptations to opioids. This lab specifically studies opioid dependence, tolerance and opioid-induced hyperalgesia. These problems limit the effectiveness of our most useful class of pain relieving medications, and support adverse outcomes such as enhanced levels of pain and addiction. Projects extend from the study of very basic molecular mechanisms to complex behavioral studies in laboratory animals. Researchers in this lab use genetic mapping to identify new pathways and contributors to the various opioid maladaptations. In addition, the work involves epigenetic mechanisms in specific neural tissues in the periphery and in the brain. This work is joined translationally to various human projects ongoing within the department.

The second area of interest is in Complex Regional Pain Syndrome (CRPS). This syndrome is addressed comprehensively using laboratory and, in some cases, human models. How activation of the innate and adaptive systems of immunity contributes to CRPS is of particular interest in this lab. Ongoing projects have been designed to determine how cytokines, growth factors and autoantibodies support the various components of CRPS. In addition, researchers are investigating the transition of the syndrome from its acute phases to its more chronic form, in which neuroplastic changes within the CNS support alterations in mood, anxiety and memory as well as ongoing pain.

Principal Faculty: David Clark, MD, PhD.

This laboratory studies molecular theories of anesthesia and alcohol. Researchers build molecular models of ligand-gated ion channels and then perform molecular dynamics calculations of anesthetic binding. Training is offered in analytical techniques, including mass spectrometry, high-pressure liquid chromatography, gas chromatography and radioactive labeling. Metabolic studies employ cell culture, preparation of cell membrane fractions and reconstituted cytochrome P-450.

Research projects can be tailored to suit individual interests and the background of the Fellow. Possible projects include treatment of rat liver hepatocytes in culture with suspected liver necrosis-inducing metabolites, raising antibodies to hepatocyte surface antigens and studying neutrophil-hepatocyte interactions.

Principal Faculty: James R.Trudell, PhD.

This laboratory's current transformative research efforts focus on studying immune health in the context of surgery and anesthesia. This interest stems from previous work elucidating the modulation of inflammatory responses by anesthetic and analgesic drugs. The aim of studying immunity in patients undergoing surgery is to identify immune phenotypes predictive of aversive postoperative outcomes, including protracted recovery and infection.

The lab’s major working hypotheses are that:

• 1. specific immune phenotypes will predict the risk for developing postoperative complications
• 2. immune phenotyping will lead to the discovery of mechanisms aggravating or alleviating such risk
• 3. gained knowledge will allow the devising of immune-modulatory strategies mitigating such risk

Mass cytometry (CyTOF), proteomics, and functional ex-vivo immune assays are the major molecular tools for the systems-based numerical and functional exploration of the circulating immune system.

Principal Faculty: Martin Angst, M.D.