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ARRA Investments in Sjögren’s Syndrome Autoimmune Disease

Public Health Burden
In healthy individuals, the body’s immune system plays a protective role.  However, in persons with an autoimmune disease, the body attacks itself.  Sjögren’s syndrome is a systemic autoimmune disease affecting between one and four million or more Americans; it is one of the most prevalent autoimmune disorders. Nine out of 10 patients are women.  The disease results in irreversible salivary gland tissue damage and loss of saliva.  With the loss of saliva, the oral cavity is highly susceptible to infections; rampant caries, oral pain and discomfort, and that can result in a reduced quality of life for patients.

Basic Research
Sjögren’s syndrome is a complex disease that involves interplay of genetic and environmental factors. By understanding the big picture of what, when, and how the disorder develops, one could begin to predict the course of the condition, and to design prevention and interventions strategies.  Varieties of ARRA funded grants in basic research are underway to better understand and manage this condition.
  • One project is studying high-priority candidate genes in 2800 Sjögren’s syndrome cases and controls to identify genes involved in the disorder in order to gain insight into the potential causes of this complex, multi-factorial disorder.1
  • Another grant is applying mathematical modeling and simulation to describe in great detail the molecular changes during onset and progression of Sjögren’s syndrome.2
  • Two projects have been supplemented to accelerate the progress in identifying the molecular and cellular mechanisms of how salivary gland cells die.3,4
  • Sjögren’s syndrome, as well as radiation therapy for head and neck cancers, involves salivary gland destruction. Several projects are investigating how salivary structure and function could be restored, even after massive damage. One study is studying how to tip the balance between survival and death of salivary gland cells by understanding a process called “autophagy.” 5
  • Two other projects are experimenting with modulating the cellular signaling pathway in salivary gland stem and progenitor cells augment the capacity of these cells to proliferate and differentiate. 6, 7
  • One project is working to identify candidate strategies for protecting human salivary (and lacrimal) tissue from the effect of Sjögren’s syndrome by specifically determining the effectiveness and mode of action of a non-toxic pharmacological agent found in green tea for early intervention and prevention.8
  • Another study is cataloging the major proteins expressed during salivary gland development over time and across the different parts of the gland. The data will create a molecular atlas of salivary gland development that serves as a reference for future studies of normal and abnormal salivary gland functions. 9

  1. 1R01DE018209-01A1 -- Susceptibility Genes in Primary Sjogren's Sydrome -- Moser, Kathy L. -- (OK)
  2. 1R01DE019255-01 -- Systems Approach to Sjogren's Syndrome Pathogenesis (SASSP) -- Wong, David T -- (CA)
  3. 3R37DE012354-12S1 -- Apoptosis in Sjogrens Syndrome -- Rosen, Antony -- (MD)
  4. 3R01DE015648-07S1 -- PKCdelta and Salivary Gland Apoptosis -- Reyland, Mary Elaine -- (CO)
  5. 1RC1DE020335-01 -- Autophagy & Functional Restoration of Irradiated Salivary Glands -- Limesand, Kirsten H -- (AZ)
  6. 1RC1DE020595-01 -- Modulating Wnt and Hedgehog Pathways for Functional Restoration of Salivary Gland -- Liu, Fei -- (TX)
  7. 3R01DE007389-21A1S1 -- The Regulation of Salivary Gland Regeneration by P2Y2 Nucleotide Receptors -- Weisman, Gary Andrew -- (MO)
  8. 1R15DE019836-01 -- EGCG intervention in a Sjogren’s Syndrome model prior to disease onset -- Hsu, Stephen De -- (GA)
  9. 1RC1DE020402-01 -- A high-resolution in situ proteomics atlas of salivary gland development -- Larsen, Melinda -- (NY)

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