Tag: Open Medicine Foundation

From Open Medicine Foundation.

We are proud to announce the establishment of another ME/CFS Collaborative Research Center. This research initiative, which includes participants from Harvard Medical School (HMS) affiliated hospitals is supported by the Open Medicine Foundation (OMF). The participating HMS Institutions include the Massachusetts General Hospital (MGH), Brigham and Women’s Hospital (BWH), & Beth Israel-Deaconess Medical Center (BIDMC). The new initiative begins with a dozen faculty from the three Harvard Institutions together with critical collaborators from the University of Birmingham, England and University of Nottingham, England, who comprise the MRC-Arthritis Research UK Centre for Musculoskeletal Aging Research, as well as long term highly valued collaborators in the fields of proteomics and metabolism from the Pacific Northwest National Laboratory (PNNL). (Full faculty listing below.)

This new Collaborative Center seeks to conduct basic science mechanistic studies with very high priority. This research focus will discover and understand the multi-omic signature of muscle biopsies of ME/CFS patients during their recovery from mild to moderate muscular stress, by comparison to healthy individuals’ signatures at baseline, during recovery from muscular stress, and during immobilization. Our hypothesis is that the inflammation-related recovery mechanisms in ME/CFS patients are dysregulated, and that this delays recovery from post-muscular stress. In addition to the direct tissue studies, both structural and functional neuroimaging will be conducted at the very advanced MGH/HMS imaging center, the Martinos Center for Biomedical Imaging (www.nmr.mgh.harvard.edu). This will allow testing of hypotheses related to neuro-immune interactions, including exaggerated vagus nerve signaling, microglial activation, and disrupted autonomic and metabolic functioning in the central nervous system.

These clinical research studies are designed to characterize the multi-omic signature (genomic, proteomic, metabolomic, as well as ultrastructural morphology) of ME/CFS patients as compared to those in healthy individuals who are recovering from muscular stress. The proteomic, phosphoproteomic, and metabolomic studies will be conducted at the PNNL. These comparisons will be correlated with the neuroimaging results with the intent to identify biomarkers and suggest drug targets for use in the development of therapeutics for ME/CFS.

This new Collaborative Center also will seek support to develop an infrastructure for rigorous clinical investigations to identify and fast track promising potential treatments through clinical trials. This clinical research center working with the OMF-supported Stanford ME/CFS Collaborative Center also represents a unique opportunity to establish standards and infrastructure for rigorous clinical investigations and trials in ME/CFS. The Center will be designed to evaluate the potential for new ME/CFS therapeutics and to conduct well designed, CRO-supervised, pivotal clinical trials for those novel promising compounds.

Participating Faculty:

The faculty participating in this new collaborative initiative are listed below along with brief introductions to follow.

Stanford University University of Birmingham (U Birmingham)
Ron Davis, PhD Janet Lord, PhD
Massachusetts General Hospital (MGH) University of Nottingham (U Nottingham)
Ronald Tompkins, MD, ScD Philip Atherton, PhD
Wenzhong Xiao, PhD Paul Greenhaff, PhD
Donna Felsenstein, MD
Jonathan Friedstat, MD
Daniel Irimia, MD, PhD Brigham & Women’s Hospital (BWH)
Amel Karaa, MD David Systrom, MD
Michael VanElzakker, PhD Anthony Komaroff, MD
H. Shaw Warren, MD
Yongming Yu, MD, PhD
Andrew Alexander, MBA Pacific Northwest National Laboratory (PNNL)
Richard Smith, PhD
BI Deaconess Medical Center (BIDMC) Jon Jacob, PhD
Janet Mullington, PhD Wei-jun Qian, PhD

Ronald Tompkins, MD, ScD, Sumner M. Redstone Professor of Surgery at HMS and MGH, is a surgeon and scientist who also trained at the Massachusetts Institute of Technology (MIT) receiving a ScD in Chemical Engineering. Dr. Tompkins has been the Chief of the MGH Burn and Trauma Services as well as the Chief of Staff, Shriners Hospitals for Children – Boston for more than 20 years. Dr. Tompkins has been active in medical research supported by more than $200M from the NIGMS in the fields of inflammation and metabolism with emphasis on genomics, proteomics, and small molecule metabolomics. Dr. Tompkins has collaborated for more than two decades with Dr. Ron Davis of the Stanford Genome Technology Center (Department of Biochemistry). Dr. Tompkins has actively participated on the Scientific Advisory Board of OMF since its establishment.

Wenzhong Xiao, PhD, Associate Professor of Surgery (Bioinformatics) at HMS and MGH, directs the MGH Inflammation & Metabolism Computational Center and leads the Computational Genomics Group at Stanford Genome Technology Center. Dr. Xiao received his PhD from the University of California Berkeley. Dr. Xiao develops bioinformatic and statistical tools for use in understanding human diseases, especially in studies of immuno-metabolic response. He focuses on integrative analysis and interpretation of multi-dimensional molecular, cellular, and clinical data of many types of patients, including those with ME/CFS. Dr. Xiao’s expertise will be essential for the interpretation of the massive data sets that will be collected in this project.

Donna Felsenstein, MD, Physician in Medicine and Assistant Professor of Medicine at HMS and MGH, is a senior attending in the Infectious Disease Unit at MGH. She has been diagnosing and caring for patients with ME/CFS since 1979. She has a large number of ME/CFS in her clinical practice, some of whom she has followed for more than 20 years. Dr. Felsenstein has participated in several clinical research studies on ME/CFS. Her clinical expertise in evaluating, diagnosing and treating patients with ME/CFS will be highly valued in the new OMF Center.

Jonathan Friedstat, MD, Assistant Professor of Surgery at HMS and MGH, is an plastic surgeon who has been well-trained in clinical trial protocols and research. His expertise and competence will be essential for proper conduct of the muscle biopsies.

Daniel Irimia, MD, PhD, Associate Professor of Surgery at HMS and MGH, is a longtime collaborator whose primary interest is in the role of neutrophils in sepsis. Daniel has developed an assay using neutrophil behavior within a microfluidic circuit that predicts sepsis with a high degree of precision (Nature Biomedical Engineering 2:207–214, 2018). Daniel’s expertise in neutrophils and neutrophil extracellular traps (NETs) will be important to clinical research in ME/CFS going forward.

Amel Karaa, MD, Assistant Professor of Pediatrics at HMS and MGH, is a board-certified pediatrician with specialty in medical genetics. This is an expertise that is very much needed in our MECFS research for many reasons but particularly because many mutations are and have been discovered but there is little medical expertise to assist us to better understand the medical implications of these mutations. She treats many ME/CFS patients in the MGH Mitochondrial Disorders Clinic will be critical to coordinate and recruit patients as well as interpret the multiple genomic findings in patients. In addition, she is critical to coordination with the mitochondrial genomic specialists at the MGH Center for Genomic Medicine.

Michael VanElzakker, PhD, Research Fellow at the MGH and HMS Martinos Center for Biomedical Imaging in the Neurotherapeutics Division, and lecturer at Tufts University. As a graduate student, Dr. VanElzakker wrote an influential hypothesis paper on the potential role of the vagus nerve in ME/CFS that has now been downloaded more than 10,000 times. Dr. VanElzakker’s expertise in neuroscience is focused on identifying abnormal patterns in brain metabolism, inflammation, structure, and function in this condition. He has enthusiastically engaged the ME/CFS community as both a scientist and patient advocate. Dr. VanElzakker will be critical to develop and conduct the neuroimaging clinical studies with the Martinos Center, which is one of the most advanced neuroimaging centers in the world.

H. Shaw Warren, MD, Physician and Pediatrician at MGH and Associate Professor of Pediatrics at HMS, is an internal medicine physician with expertise in pediatric infectious disease. His role follows his extensive experience in research in inflammation, endotoxemia, and genomics. He currently directs a DARPA funded project entitled SPIRIT, which probes the differences in the host’s responses to infectious agents in multiple mammalian species. His research competence in these fields together with his clinical experience with ME/CFS patients will make a tremendous contribution to the new initiative.

Yong Ming Yu, MD, PhD, Associate Professor of Surgery at MGH and HMS, is classically trained in nutritional biochemistry at the Massachusetts Institute of Technology (MIT). He is highly experienced in the in metabolism following the severe stress of injury and inflammation, prolonged fasting or nutritional depletion, and immobilization. His understanding of metabolism will be essential to understand the metabolic findings seen in ME/CFS patients.

David Systrom, MD, Assistant Professor of Medicine at BWH and HMS, is a internal medicine and pulmonary disease physician with certification in critical care medicine. Dr. Systrom’s expertise focuses on cardiopulmonary function resulting in highly specific phenotype characterization of ME/CFS patients particularly those with POTS syndrome. His research involving ME/CFS particularly seeks to discover the link between small fiber polyneuropathy (nerve damage) and exertional intolerance. His participation in this new initiative has tremendous value to more precisely characterize ME/CFS patients with their ME/CFS disease characteristics and to study these well-characterized patients in clinical trials.

Anthony Komaroff, MD, Distinguished Simcox-Clifford-Higby Professor of Medicine at HMS, and Senior Physician at BWH. He served for 15 years as Director of the Division of General Medicine and Primary Care at BWH. Dr. Komaroff’s contributions to ME/CFS include his pioneering work in the definition of, epidemiologic studies of the prevalence of the illness, and assessment of the biological changes present in chronic fatigue syndrome. He will be a consultant to the new OMF Center and he currently leads the human studies core at the Columbia NIH-funded ME/CFS Collaborative Center.

Janet Mullington, PhD, Professor of Neurology at HMS and BIDMC, is Director of the BIDMC Clinical Research Center and directs the HMS Human Sleep and Inflammatory Systems Laboratory. Dr. Mullington is a well-respected expert in the physiological and neurobehavioral effects of insufficient and/or inadequate quality sleep including autonomic, metabolic and inflammatory system consequences of sleep loss. Her perspective and participation will be extremely helpful for our new initiative particularly as issues relate to the very common symptoms of non-restorative sleep and sleep disorders in ME/CFS patients.

Janet Lord, PhD, Professor of Immunology, University of Birmingham, and Chair of Immunology. Dr. Lord directs the Institute of Inflammation and Ageing and the MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research. Dr. Lord brings together fundamental scientists and clinicians to translate the understanding of inflammation to new treatments for chronic age-related inflammatory diseases. Her research focuses on the dysregulation of immunity in old age, and in particular, the decline in neutrophil function and how this compromises the response to infection and tissue injury. Her knowledge and leadership in the natural findings of inflammation upon tissues will be critical to understand many of the findings that are discovered in ME/CFS patients in this new initiative. She brings two essential colleagues to the new OMF Center, Drs. Paul Greenhaff and Philip Atherton.

Paul Greenhaff, PhD, Professor of Muscle Metabolism, University of Nottingham, is a physiologist and the Deputy Director of the MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research (Nottingham). Dr. Greenhaff is also an active member of the ARUK Centre for Sport, Exercise and Osteoarthritis and the Musculoskeletal Disease theme of the Nottingham NIHR Biomedical Research Centre. He is classically trained in the field of muscle metabolism with research interests centered on the loss of muscle mass and the dysregulation of metabolism in ageing, inactivity, inflammation, trauma and disease, and strategies to offset these pathophysiological events. His expertise will be critical to understand what the nutritional and sedentary effects are contributing to patients with ME/CFS in the new initiative.

Philip Atherton, PhD, Professor of Clinical, Metabolic & Molecular Physiology, University of Nottingham is classically trained in stable isotope nutritional biochemistry, providing tremendous experience in the inflammation and metabolism fields. His laboratory is in the Royal Derby Hospital under the auspices of our UK Medical Research Council/Arthritis Research UK Centre of Excellence for musculoskeletal ageing research and the newly awarded NIHR Biomedical Research Centre (BRC) under a clinical musculoskeletal theme. His research seeks identification of central mechanisms regulating metabolism in human musculoskeletal tissues. These interests and expertise will be critical to the new OMF Center.

Richard Smith, PhD, Battelle Fellow and Director of Proteome Research at PNNL, is also the Director of the NIGMS Biomedical Technology Research Resource for Proteomic Integrative Biology and the DOE ‘Pan-omics’ Program at PNNL. He is a pioneer in mass spectroscopy and proteomics technologies, is a long term collaborator with the faculty at MGH, and is the author or co-author of more than 1,000 peer-reviewed publications and more than 50 US patents. His continued development and application of innovative mass spectrometry technologies will be critical in identifying the proteomic and metabolic signatures of patients with ME/CFS in the new initiative.

Jon Jacobs, PhD, Senior Research Scientist at PNNL, is currently the associate director of the NIGMS Biomedical Technology Research Resource for Proteomic Integrative Biology and the collaborative analytical support for the MGH lead DARPA project SPIRIT. His expertise lies in the development and application of advanced proteomic analysis techniques, specifically in the context of clinical studies focusing on complex disease signatures including inflammatory responses and chronic liver disease. Dr. Jacobs has a history of productive long term collaborations with MGH faculty through the application of proteomic approaches. His role will be to accurately direct the application of the advanced analytical technologies at PNNL towards the ME/CFS patient clinical samples for signature characterization.

Wei-Jun Qian, PhD, is a bioanalytical chemist whose research centers primarily on global and targeted quantification of proteins and post-translational modifications (PTMs), particularly redox modifications and phosphorylation. Dr. Qian is currently a Senior Staff Scientist and the Team Lead for Proteomics at PNNL, and has been the recipient of the NIH Director’s New Innovator Award and the Presidential Early Career Award for Scientists and Engineers (PECASE). Dr. Qian’s team has significantly advanced the sensitivity and robustness of selected reaction monitoring (SRM)-based targeted quantification, thus enabling the direct quantification of extremely low-abundance proteins, protein isoforms, and PTMs for broad biomedical applications. Dr. Qian’s expertise in PTM and SRM efforts will directly benefit analysis of ME/CFS patient samples.

From Open Medicine Foundation.

I am proud to share with you the new and expanding research projects that we are funding this year. As we have recently shared, research is quickly expanding. We look forward to continuing to share updates with you about our exciting Collaborative Research Centers at Stanford and Harvard and all of our research projects. We invite you to continue to support our efforts to fund these teams of expert scientists pursuing our common goal: End ME/CFS.

We are confident that our research is leading us to answers. To keep this momentum growing, we count on your support. Whether you can donate $5, $500, or $5,000, every gift makes a difference in supporting research and delivering hope. Please donate today.

And please help us to grow by spreading our news. Forward this email to your family and friends and invite them to personally sign up to receive our news in their inbox to stay informed.

I am looking forward to seeing all who are attending the Invest in ME Research International Conference next week in London. I will be attending the Conference and the Biomedical Research into ME Colloquium along with 6 of our scientific advisory board members. If you are attending, please come visit us at our table on June 1st so that we can say hello in person.

With hope for all,

Linda Tannenbaum
CEO/President
linda@omf.ngo

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.
• 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. (More) Read 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 9 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 will take place on Saturday, September 29. At the Community Symposium, the scientists will update patients and any interested 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. Come hear from our amazing team in person. If you can’t attend, the symposium will be livestreamed. Registration information for the Community Symposium will be coming out soon.