September 24, 2009: WPI Awarded Prestigious NIH R01 Grant
New Strategies to Decipher the Pathophysiology of Chronic Fatigue Syndrome
WPI Research Director Dr. Judy Mikovits and collaborator Dr. Jonathan Kerr
of St. George's College in London were awarded this $1.6 million grant by
the National Institute of Allergy And Infectious Diseases. This 5 year grant
will provide critical support for the ongoing research into the causes and
diagnosis of neuro-immune diseases.
~~~~~~~~~~~~~
[Well done to anyone who has previously supported funds that supported
research by Drs Mickovits and Kerr - most likely this helped them get this
grant. Tom K]
From: http://projectreporter.nih.gov/project_info_history.cfm
Project Number: 1R01AI078234-01A2
Principal Investigator(s): MIKOVITS, JUDY ANNE
Title: NEW STRATEGIES TO DECIPHER THE PATHOPHYSIOLOGY OF CHRONIC FATIGUE
SYNDROME
Awardee Organization: WHITTEMORE PETERSON INSTITUTE
Abstract Text:
(I've spaced this out to make it easier to read)
DESCRIPTION (provided by applicant):
Chronic Fatigue Syndrome (CFS) is a complex disease estimated to affect
between 0.5%-2% of the population in the Western world. Its pathogenesis is
thought to involve both inherited and environmental (including viral)
components, as with other chronic inflammatory diseases such as, multiple
sclerosis, rheumatoid arthritis, and atherosclerosis. Consistent with this
chronic inflammatory context, CFS patients are known to have a shortened
life-span and are at risk for developing lymphoma. We hypothesize that
chronic inflammatory stimulation from active and recurrent infections of
multiple viruses on a susceptible host genetic background leads to the
pathogenesis characterized by CFS. The overall goal of this research project
is to define these viral and host parameters in European and American
cohorts of CFS patients that correlate with distinct disease phenotypes,
including the development of mantle cell lymphoma (MCL) in a subgroup of the
American cohort.
In Aim 1) we will identify and confirm novel viral infections in European
and American CFS patient cohorts.
1.1) we will use two complementary methods for detection of novel virus
mRNA: massive parallel signature sequencing (MPSS) and a custom DNA
microarray.
1.2) Quantitative polymerase chain reaction Q-PCR will be used for
confirmation of virus gene expression.
1.3) immortalized cell lines will be developed to isolate virus and
elucidate links between virus and host cell gene expression.
In Aim 2), we will elucidate genetic factors of susceptibility and the
dysregulation of the host defense system. Specifically, we will determine:
2.1) PBMC gene expression of 88 human genes previously confirmed as being
differentially expressed in CFS
2.2) serum chemokine and cytokine profiles using multiplex suspension
antibody arrays on a Luminex platform
2.3) HLA, KIR genotypes and whole genome SNP profiles
2.4) Defects in the type I Interferon signaling pathway.
In each subaim both cohorts will be compared to normal and disease controls
using specimens of serum and PBMC taken at multiple time-points from
individual patients and taken from our unique and extensive sample
repository. This study will provide information necessary for development of
treatment and diagnostic strategies for distinct subgroups of CFS patients,
and may identify novel virus associations, genetic signatures and
biomarkers, which can predict the development of MCL, thus enabling use of
preventive therapeutics.
PUBLIC HEALTH RELEVANCE: The proposed research will provide significant
insight into the disease mechanisms of Chronic Fatigue Syndrome so accurate
testing and specific treatments can be developed with a goal of curing the
disease and preventing life-threatening complications.
Public Health Relevance Statement:
PROJECT NARRATIVE The proposed research will provide significant insight
into the disease mechanisms of Chronic Fatigue Syndrome so accurate testing
and specific treatments can be developed with a goal of curing the disease
and preventing life-threatening complications.
Project Terms:
Active Follow-up; Acute; Affect; American; Analysis, Data; Antibodies;
Atheroscleroses; Atherosclerosis; Atherosclerotic Cardiovascular Disease;
Atrophic Arthritis; Blood Plasma; Blood Serum; CDC; Cell Culture Techniques;
Cell Line; Cell Lines, Strains; CellLine; Cells; Centers for Disease
Control; Centers for Disease Control (U.S.); Centers for Disease Control and
Prevention; Centers for Disease Control and Prevention (U.S.); Chronic;
Chronic Fatigue Disorder; Chronic Fatigue Syndrome; Chronic Fatigue and
Immune Dysfunction Syndrome; Chronic Fatigue-Fibromyalgia Syndrome; Complex;
Custom; Cytokines, Chemotactic; DNA Chips; DNA Microarray; DNA Microarray
Chip; DNA Microchips; DNA Sequence Rearrangement; Data; Data Analyses; Data
Set; Dataset; Defect; Detection; Development; Diagnostic; Disease; Disorder;
Dysfunction; Encephalomyelitis, Myalgic; European; Functional disorder; Gene
Expression; Genes; Genetic; Genome; Genotype; Germinoblastoma; Goals;
Hereditary; Homologous Chemotactic Cytokines; Host Defense; Human; Human,
General; Immune; Immune response; Individual; Infection; Infectious
Mononucleosis-Like Syndrome, Chronic; Inflammatory; Inflammatory Arthritis;
Inherited; Intercrines; Interferon Type I; Length of Life; Life; Link;
Longevity; Lymphoma; Lymphoma (Hodgkin's and Non-Hodgkin's); Lymphoma,
Lymphocytic, Diffuse, Intermediate Differentiated; Lymphoma, Lymphocytic,
Diffuse, Poorly-Differentiated; Lymphoma, Malignant; Lymphoma, Mantle-Cell;
Lymphoma, Small-Cell, Centrocytic; MS (Multiple Sclerosis); Malignant
lymphoma, lymphocytic, intermediate differentiation, diffuse; Man
(Taxonomy); Man, Modern; Mantle-Zone Lymphoma; Messenger RNA; Methods;
Multiple Sclerosis; Neurologic; Neurological; Organ System; PBMC; PCR;
Pathogenesis; Patients; Peripheral Blood Mononuclear Cell; Phenotype;
Physiopathology; Plasma; Play; Polymerase Chain Reaction; Population;
Postviral Fatigue Syndrome; Predisposition; Preventive; Process; R01
Mechanism; R01 Program; RNA, Messenger; RPG; Rearrangement; Recurrence;
Recurrent; Research; Research Grants; Research Project Grants; Research
Projects; Research Projects, R-Series; Research Specimen;
Reticuloendothelial System, Serum, Plasma; Reticulolymphosarcoma; Rheumatoid
Arthritis; Risk; Role; Royal Free Disease; SIS cytokines; SUBGP; Sampling;
Sarcoma, Germinoblastic; Sclerosis, Disseminated; Serum; Serum, Plasma;
Signal Pathway; Source; Specimen; Stratification; Subgroup; Susceptibility;
Suspension substance; Suspensions; System; System, LOINC Axis 4; Testing;
Therapeutic; Time; Transmission; United States Centers for Disease Control;
United States Centers for Disease Control and Prevention; Variant;
Variation; Viral; Viral Diseases; Virus; Virus Diseases; Viruses, General;
Western World; association test; atheromatosis; atherosclerotic vascular
disease; biomarker; body system; chemoattractant cytokine; chemokine;
cohort; cultured cell line; cytokine; disease control; disease phenotype;
disease/disorder; disorder control; follow-up; genetic association; host
response; immortalized cell; immunoresponse; insight; insular sclerosis;
intervention development; latent infection; life span; lifespan; mRNA;
novel; novel virus; pathophysiology; prevent; preventing; public health
relevance; repository; social role; suspension; therapy development;
transmission process; treatment development; viral infection; virus culture;
virus infection
Contact PI Information:
Name: MIKOVITS, JUDY ANNE
Email: jamikovits@gmail.com
Title: RESEARCH DIRECTOR
Organization:
WHITTEMORE PETERSON INSTITUTE, 6600 North Wingfield Pkwy, Sparks, NV 89436
Congressional District:
State Code: NV
District: 02
Other PI Information:
KERR, JONATHAN RICHARD
Other Information:
RFA/PA: PA-08-246
Study Section: ZRG1 Project Start Date: 28-SEP-2009 Project End Date:
31-AUG-2014
Fiscal Year: 2009 Budget Start Date: 28-SEP-2009 Budget End Date:
31-AUG-2010
Administering Institutes or Centers: NATIONAL INSTITUTE OF ALLERGY AND
INFECTIOUS DISEASES
Project Funding Information for 2009: Total Funding: $335,600
Year Funding IC FY Total Cost by IC
2009 NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES $335,600
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