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Research authored by Dr. Underhill
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List of Publications via PubMed
(NIH National Library of Medicine)
List of Publications via PubMed
(NIH National Library of Medicine)
| T. Michael Underhill, Ph.D., research |
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Website 2009 conference abstract will be posted shortly.
Delineation of Regulatory Networks Underlying BMP Action in Chondrogenesis
Abstract 2005 MHE Conference
T. Michael Underhill1, Linsay M. Drysdale2, Konstantina Karamboulas1,
Matthew F. Cowan1, Jian Wang3, William A. Horton4 and Lisa M. Hoffman2
1 Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada, V6T 1Z3; 5C1 2
Department of Physiology, Faculty of Medicine & Dentistry, University of Western Ontario, London, ON,N6A 3 Robarts Research
Institute, 100 Perth Dr., London, ON, Canada, N6A 5K8;4 Shriner’s Children’s Hospital, 3101 SW Sam Jackson Park Road,
Portland, OR, USA, 97239
The BMP and GDF signaling pathways have well-established and essential roles within the developing skeleton in coordinating
formation of cartilaginous anlagen. However, identification of bona fide
targets that underlie the action of these signaling molecules in chondrogenesis has remained elusive.
Using microarray-based methods coupled with functional profiling, we have identified the retinoic acid (RA) synthesis enzyme,
Aldh1a2, as a principal target of BMP signaling—prochondrogenic BMPs or GDFs lead to attenuation of Aldh1a2 expression and
consequently, reduced activation of the retinoid signaling pathway.
Consistent with this, antagonism of retinoid signaling phenocopies BMP4 action, whereas RA inhibits the chondrogenic
stimulatory activity of BMP4. Further, moderate fold changes in endogenous retinoid signaling (< 4.5 fold) are sufficient to
regulate expression of the chondroblast phenotype.
In aggregate, these results establish a hierarchical relationship between the BMP and retinoid signaling pathways in
chondrogenesis.
These results will be presented along with additional findings that provide a molecular framework for understanding BMP action
in the chondrogenic program.
This research was supported by grants to T.M.U. from the Canadian Institutes of Health Research and the Canadian Arthritis
Network
Delineation of Regulatory Networks Underlying BMP Action in Chondrogenesis
Abstract 2005 MHE Conference
T. Michael Underhill1, Linsay M. Drysdale2, Konstantina Karamboulas1,
Matthew F. Cowan1, Jian Wang3, William A. Horton4 and Lisa M. Hoffman2
1 Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada, V6T 1Z3; 5C1 2
Department of Physiology, Faculty of Medicine & Dentistry, University of Western Ontario, London, ON,N6A 3 Robarts Research
Institute, 100 Perth Dr., London, ON, Canada, N6A 5K8;4 Shriner’s Children’s Hospital, 3101 SW Sam Jackson Park Road,
Portland, OR, USA, 97239
The BMP and GDF signaling pathways have well-established and essential roles within the developing skeleton in coordinating
formation of cartilaginous anlagen. However, identification of bona fide
targets that underlie the action of these signaling molecules in chondrogenesis has remained elusive.
Using microarray-based methods coupled with functional profiling, we have identified the retinoic acid (RA) synthesis enzyme,
Aldh1a2, as a principal target of BMP signaling—prochondrogenic BMPs or GDFs lead to attenuation of Aldh1a2 expression and
consequently, reduced activation of the retinoid signaling pathway.
Consistent with this, antagonism of retinoid signaling phenocopies BMP4 action, whereas RA inhibits the chondrogenic
stimulatory activity of BMP4. Further, moderate fold changes in endogenous retinoid signaling (< 4.5 fold) are sufficient to
regulate expression of the chondroblast phenotype.
In aggregate, these results establish a hierarchical relationship between the BMP and retinoid signaling pathways in
chondrogenesis.
These results will be presented along with additional findings that provide a molecular framework for understanding BMP action
in the chondrogenic program.
This research was supported by grants to T.M.U. from the Canadian Institutes of Health Research and the Canadian Arthritis
Network
| Photo's taken during the Third International MHE Research Conference |
