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ME/CFS and related chronic complex diseases

OMF-Funded Research 2018


OMF-Funded Research 2018


ME/CFS COLLABORATIVE RESEARCH CENTER AT STANFORD

OMF is continuing to fund the ME/CFS Collaborative Research Center at Stanford. These are the projects currently underway:

  • T cells and immunology

    Michael Sikora, in collaboration with Mark Davis, PhD, Lars Steinmetz, PhD, and Ron Davis, PhD, at Stanford University, will examine the role of T cells and immune-related genes in ME/CFS. This may help address the outstanding question of whether ME/CFS is an autoimmune or infectious disease, or simply an activation of the immune system. Click here to read more about the plans for this study. Click here to hear Dr. Mark Davis talk about T-cell research.

  • Extended big data study in families

    Fereshteh Kenari Jahaniani, PhD, in collaboration with Mike Snyder, PhD, and Ron Davis, PhD, of Stanford University, are generating multiple large datasets (genomics, gene expression, metabolomics, proteomics, and cytokines) in a cohort of patients and their families. By comparing patients to healthy blood relatives, we are more likely to understand what genes cause or contribute to the development of ME/CFS. This data will also be integrated with the Severely ill Patients (Big Data) Study (SIPS) , providing important validation and extension of those findings. Read and watch more about the multi-omics approach.

  • Diagnostic and drug-screening technology development

    Four technologies are being developed that could provide a biomarker for ME/CFS. Dr. Davis’s team is dedicated to developing these into inexpensive tests that can be easily used in a doctor’s office. In the future, all patients will be measured on all of these diagnostic platforms, enabling us to compare their efficacy and determine what combination of them will be most useful to export for diagnostic testing. Click here to read more about the plans for this study.

    1. Nanoneedle: Rahim Esfandyarpour, PhD, in collaboration with Ron Davis, PhD, is validating and further developing the nanoneedle biosensor platform, which has shown promise as a blood-based diagnostic for ME/CFS. This is a nanofabricated device that measures electrical impedence from a drop of blood. Thus far, this test is able to distinguish ME/CFS patients from healthy controls. The technology will be optimized for easy clinical adoption and scaled up so that numerous FDA-approved drugs can be simultaneously screened as potential treatments. Click here to read more about why a blood-based diagnostic could be a game-changer.
    2. Magnetic Levitation Device: Gozde Durmus, PhD, in collaboration with Ron Davis, PhD, has been developing a magnetic levitation device. This device uses a ferrofluid in a glass capillary surrounded by permanent magnets. This generates a density gradient and cells move to their respective densities in the capillary. Their position is imaged by a camera from a smart phone. It was discovered that white blood cells from ME/CFS patients are less dense than healthy controls. One patient was followed for several months, consistently showing a light density. It was further observed that there was a correlation between the lightness of the cells and the severity of symptoms. This could be a very inexpensive diagnostic test, and more patients will be tested in 2018.
    3. Red Blood Cell Deformability Test: Mohsen Nemat-Gorgani, PhD, of Stanford University, and Anand Ramasubramanian, PhD, of San Jose State University, in collaboration with Ron Davis, PhD, are developing a micro-fluidic device that measures blood flow and deformability of red blood cells. In preliminary results, the red blood cells of ME/CFS patients and healthy controls differ in their time of entry into a capillary, rate of movement through the capillary, and the extent of deformation of the cell in the capillary. This has the potential to be yet another biomarker that would only require a drop of blood. (More)
    4. Mitochondrial Function Test: Julie Wilhelmy, in Dr. Davis’s lab, has developed a protocol using the Seahorse instrument that measures mitochondrial function. This protocol reveals a significant difference between activated T-cells of ME/CFS patients and healthy controls. The instrument is commercially available, which will allow other laboratories to easily reproduce our results.
  • Metabolic Trap

    Dr. Robert Phair, PhD, of Integrated Bioinformatics, Inc, has been working with Dr. Davis’s team at Stanford. He has found a metabolic pathway in ME/CFS patients that he hypothesizes to be stuck in a “trap” in an unhealthy state. His metabolic trap hypothesis emerged from genetic and metabolomics data from the Severely ill Patients Study (SIPS) combined with published enzymatic kinetics using mechanistic computational modeling. Dr. Phair and the team are eager to test this hypothesis as fast as possible, as it could be the underlying cause of ME/CFS and lead to effective treatment. (MoreRead Health Rising’s article about the Metabolic Trap

OTHER EXCITING PROJECTS FUNDED BY OMF:

ME/CFS COLLABORATIVE RESEARCH CENTER AT HARVARD

OMF has newly awarded a grant totaling $1.8 million to establish a new ME/CFS Collaborative Research Center at Harvard. The new Harvard Center will be led by OMF Scientific Advisory Board members Ronald G. Tompkins, MD, ScD, and Wenzhong Xiao, PhD, and will work synergistically with the ME/CFS Collaborative Research Center at Stanford led by Ronald W. Davis, PhD, of Stanford University, also funded by OMF. All science funded by OMF continues to be under the overall direction of our Scientific Advisory Board, directed by Ron Davis. Click here for more information.

Stanford ME/CFS Data Management and Coordination Center

OMF is also funding the expansion of the Stanford Data Center for the Severely Ill Patients (SIPS) Study to encompass all the data from the Stanford and Harvard ME/CFS Collaborative Research Centers, as well as data from any other research we are funding. The clinical results from the SIPS are currently already open to researchers with access via our website. This expanded data center will give researchers quick access to massive amounts of research data.

Analyzing Patient Data Study

This retrospective study aims to analyze the clinical records and test results of thousands of patients from ME/CFS specialists. (More)

Hormones, Proteins, Autoantibodies

Jonas Bergquist, MD, PhD, is validating his autoantibody findings, as well as measuring proteins and steroid hormones in plasma and cerebrospinal fluid. (More)

Metabolomics Validation Study

Robert K. Naviaux, MD, PhD’s 2016 ME/CFS metabolomics study is being expanded to include additional validation studies with Oliver Fiehn, PhD, and his team at the West Coast Metabolomics Center (WCMC), University of California, Davis (UCD). (More)

Second Annual Collaborative Team Meeting on the Molecular Basis of ME/CFS at Stanford University

This year our collaborative team meeting will be expanded to three days, September 26-28. The first two days will allow for in-depth scientific discussion of recent ME/CFS research results. On the third day we will establish collaborations and discuss the most effective path forward to expedite ME/CFS research. At this groundbreaking scientific conference, over 30 international researchers will share unpublished data and ideas. Sharing unpublished data is a very effective way to accelerate the research because scientists can consider these results without waiting for publication. This interdisciplinary team of experts in numerous fields, including Nobel laureates, and several members of the National Academy of Sciences, will discuss genetics, metabolism, immunology, data integration, related diseases, drug discovery, and lessons from these and other fields for ME/CFS research.

Second Annual Community Symposium on the Molecular Basis of ME/CFS at Stanford University – September 29

The Community Symposium took place on Saturday, September 29. At the Community Symposium, the scientists updated patients and members of the public on the latest research and our progress towards understanding the molecular basis of ME/CFS and our plans for the future. The Symposium was recorded and is available on OMF’s Youtube channel for viewing.

OMF Funds Four Additional Research Projects for a Total of $241,670 (update November 2018)

Red blood cells (RBCs) transport oxygen from the lungs to the cells of your body and then carry carbon dioxide from your cells to your lungs. For RBCs to get to all these cells, they need to be able to flow through small blood vessels with minimal friction. Ultimately, this requires RBCs to be smooth, rounded, and elastic. Alterations in these properties of RBCs can occur during chronic inflammatory diseases like sepsis, and we have found that this deformability is also occurring in ME/CFS. For more information on RBC deformability, click here.

These observations along with new technology available for measuring RBC deformability prompted engineers from Stanford and their collaborators at San Jose State University to examine RBC deformability in ME/CFS. The following three projects will develop and evaluate a device to rapidly determine the ‘deformability’ of RBCs as a potential biomarker for ME/CFS.

1. Eric Shaqfeh, PhD, Department of Chemical Engineering, Stanford University –

Computer Simulation of the Effect of Membrane Rigidity on the Micro-Flows of Red Blood Cells to Create a Diagnostic for ME/CFS

The Shaqfeh group at Stanford University will produce computer 3D simulations of RBCs through a set of channels that resemble a blood circulation system. Using these simulations, the Shaqfeh group will determine how to characterize the properties of RBCs by the way they flow through these channels.

2. Anand Ramasubramanian, PhD, Biomedical, Chemical & Materials Engineering, San José State University – Erythrocyte Biomechanics in ME/CFS

The computer simulations described above will be conducted in close collaboration with the Ramasubramanian group at San Jose State University, where they are producing a microfluidics chip to estimate the properties of RBCs. A microfluidic chip is a set of tiny channels etched into a piece of material like glass or plastic and is around the size of a SIM card. Designing the microfluidic chip will require ongoing RBC simulations by the Shaqfeh group to determine the optimal set of channels to distinguish ME/CFS RBCs from normal RBCs.  The microfluidic devices suggested from the simulations will be tested at San Jose State with the ultimate goal being the creation of a sensitive diagnostic device.

3. Juan G. Santiago, PhD, Department of Mechanical Engineering, Stanford University – Computer Simulation of the Effect of Membrane Rigidity on the Micro-Flows of Red Blood Cells to Create a Diagnostic for ME/CFS

A key part of determining RBC properties in these channels will be the development of a state-of-the-art image analysis tool that can automatically identify and track the position and shape of thousands of RBCs under relaxed and stressed conditions. The Santiago group will develop this visualization technology at Stanford University.

The visualization technology developed by the Santiago group will be applied to develop a microfluidics device in conjunction with the Ramasubramanian and Shaqfeh groups.

The longer-term goal of this collaborative effort between these three groups is to produce a low-cost, disposable device to determine the rapid quantitation of deformability of the cells in a single drop of blood.

4. OMF has granted Scientific Advisory Board member, Jonas Bergquist, MD, PhD, Uppsala University (Sweden), additional funds to expand his work on targeted proteomics for neuroinflammatory markers in cerebrospinal fluid (CSF) in ME/CFS patients.

Continuing with his ongoing study of CSF from ME/CFS patients, Dr. Bergquist has recently acquired a piece of technology that significantly enhances the detection of inflammation markers. This technology has yet to be used on CSF, so this will be the world’s first test case for ME/CFS samples. Using this technology, Bergquist’s team is going to selectively test for a set of over 900 markers of neuroinflammation.

 

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