Skeletal tissues and joints can be affected by acute injury, chronic degeneration, genetic dysfunction and cancer-related defects. Andre J. van Wijnen, Ph.D., and his colleagues are working to improve the current clinical standards of care in orthopedic repair, restoration and rejuvenation of the skeleton. His research group designs and validates molecular strategies for therapeutic applications that control the ability of mesenchymal stem cells to adopt a defined cellular phenotype or to retain a self-renewing multipotent state. These studies focus on molecular mechanisms and manipulations that mediate cellular differentiation into the four principal tissues of the human joint — bone, cartilage, ligament and tendon.
- Stem cell engineering. Biological transitions during human fetal development and pathological conditions of skeletal diseases are linked to changes in gene expression. Dr. van Wijen and his colleagues leverage this principle by manipulating regulatory states of human stem cells and altering the accessibility of genes within chromosomes (epigenetics) or levels of small RNAs (microRNAs).
- In vivo modeling of human skeletal injuries and diseases. Mouse genetics and small-animal surgical models are employed to recapitulate development, injuries and congenital diseases of the human skeleton.
- Molecular phenotyping of human skeletal tissues and tumors. Dr. van Wijnen and his colleagues are working to define molecular properties of normal and diseased human skeletal tissues relevant to orthopedic oncology. This information will help define key diagnostic and prognostic parameters, improving the clinical classification of tumors and helping refine treatment options in cancers including osteosarcoma and chondrosarcoma.
- Skeletal tissue engineering. The group is developing strategies to generate skeletal tissues using stem cells for autologous transplantation, allograft rejuvenation and de novo repair with synthetic scaffolds.
- Bone biology. Dr. van Wijnen and his colleagues use human and mouse cell culture models to understand how stem cells turn into bone cells (cell fate determination during osteogenesis) and how anabolic bone cells mature into active cells that produce the collagen-rich extracellular matrix that mineralizes into bone (lineage progression of osteoblasts).
Significance to patient care
The work in Dr. van Wijnen's laboratory has immediate impact on patient care at Mayo Clinic by improving the understanding of human stem cells and expanding the repertoire of tissue-engineering applications for these cells in the orthopedic clinical realm.
Furthermore, this group contributes to the classification of orthopedic diseases — such as skeletal sarcomas and osteoarthritis — using state-of-the-art molecular parameters that include epigenetic states and microRNAs. This will improve the classification of pathological tumor grades and thus the accuracy of disease diagnosis.
Journal editor and reviewer
Dr. van Wijnen serves or has served with distinction as editor-in-chief for:
- GENE 2010-present; reviews editor, 1998-2010
- Current Molecular Biology Reports, 2013-present
- Molecular Biology Reports, 1995-2013
He also serves as an active editor for many other journals, including:
- Journal of Biological Chemistry, 2007-present
- Journal of Bone and Mineral Research, 2010-present
- Journal of Cellular Biochemistry, 1995-present
- PLOS One, 2011-present
- Critical Reviews in Eukaryotic Gene Expression, 2005-present
Dr. van Wijnen has been a reviewer for more than 100 journals in his field.
Chair and panel member, NIH and VA grant reviews
- Chair and panel member, Veterans Administration (VA) study section in endocrinology (ENDB), 2009-present
- Panel member, National Institutes of Health (NIH) review panel: Skeletal Biology Structure and Skeletal Regeneration (SBSR), 2013-present
- Panel member, NIH study sections in cell biology (CDF3/CSD/CSRS/MIST), 2000-2010
- Panel member, NIH study sections (TCB, UKGD, AMS), 2007-2011
- Panel member, NIH Special Emphasis Review panels to evaluate research projects — R01programs (P01, P30 and P50) and new investigator (R03 and K) awards, 2001-present
Dr. van Wijnen has also participated in peer review of many non-NIH and international grant applications.