3Helix Inc. proposes to develop a new peptide-based tissue staining agent for detecting denatured collagen in histopatholgical studies in this Phase I SBIR. The founders of 3Helix, Inc., Drs. Yang Li and Michael Yu, discovered a synthetic Collagen Hybridizing Peptide (CHP), which can specifically bind to the denatured collagen molecules with high affinity: the CHP peptide is able to form a stable hybridized triple helix structure only with the unraveled collagen strands but not with intact collagen molecules. The discovery of CHP, and its binding to denatured collagen, has been patented, published in multiple journals including PNAS, and its potential applications in histology have drawn significant interest from academic and industrial research communities as well as from major reagent vendors. Collagen is the major structural component of nearly all human tissues and organs, providing a sturdy and bioactive framework for cell growth and tissue formation. Although degradation of collagen takes place during normal tissue development and maintenance, excessive levels of collagen degradation and denaturation is intricately involved in a wide variety of diseases including cancer, atherosclerosis, arthritis, osteoporosis, nephritis, and fibrosis. The denatured collagen molecule is a hallmark indicator of inflammation and tissue injury in these diseases. However, this indicator is rarely used in biomedical research, due to the lack of any reagent or method that can readily detect it. Traditional collagen stains and common anti-collagen antibodies are unable to distinguish between denatured and intact collagen molecules, while other methods (e.g., in situ zymography, transmission electron microscopy) can only be applied to selective types of collagen, or require highly specialized instrument and skills. As a result, the mechanism of many of these diseases, particularly their association with collagen degradation is not well understood. In this proposed project, 3Helix will validate the feasibility of its CHP staining technique in pathological tissues from animal disease models, and compare CHP with representative conventional collagen imaging methods to demonstrate its unique capability and convenience. With successful completion of the project, 3Helix's CHP stain will be a powerful reagent for assessing tissue damage in histopathology, which could help advance the understanding of the mechanism and progression of over 30 different types of diseases, including cancer, atherosclerosis, arthritis, osteoporosis, and fibrosis. It will also lead to new diagnostics and screening tools for new therapeutics.

Public Health Relevance

The denatured collagen is a valuable indicator of many diseases that involve tissue damage, but an effective and convenient method to detect it is currently lacking. 3Helix proposes to develop a new tissue staining reagent for detecting denatured collagen. When completely developed, this new reagent, will help advance the science of a multitude of diseases including cancer, atherosclerosis, and arthritis, and will lead to new diagnostic and therapeutic screening tools for them.

National Institute of Health (NIH)
Office of The Director, National Institutes of Health (OD)
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
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Special Emphasis Panel (ZRG1)
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Contreras, Miguel A
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3helix, Inc.
United States
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Hwang, Jeongmin; Huang, Yufeng; Burwell, Timothy J et al. (2017) In Situ Imaging of Tissue Remodeling with Collagen Hybridizing Peptides. ACS Nano 11:9825-9835