Underhill

T. Michael Underhill

Professor

PhD Microbiology & Immunology (UWO)
BSc Genetics (University of Western Ontario)

Email: t.michael.underhill@ubc.ca

Office: 604-822-5833

Lab: 604-822-7252

Research Interests
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During the last few years, much has been learned about the mechanisms that regulate the formation of the skeletal tissues. Several transcription factors critical to the chondrogenic and osteogenic program have been identified, and the importance of various growth factors and cytokines in these processes is also being established. My laboratory has recently established an important role for the retinoid signaling pathway in chondrogenesis (Weston et al, 2000, J. Cell Biol.; Weston et al. 2002, J. Cell Biol.) and recent evidence from our laboratory also demonstrates an important function for this pathway in osteogenesis (Sampaio and Underhill, in preparation). To better understand the mechanisms underlying the commitment and differentiation of skeletal progenitors, my lab has employed a functional genomics approach. Traditionally, the major limitation of this approach involves efficiently defining the function of potentially hundreds of differentially-expressed candidate genes. To circumvent this problem, the Underhill lab has developed various high-content screens to facilitate the analysis of gene function in chondrogenesis and osteogenesis. In this manner, hundreds-thousands of genes can be screened for their ability to promote or inhibit these programs. This approach together with complementary strategies (ie. transcriptional profiling with arrays, automation with robotics, etc.), are currently being used to delineate the molecular regulatory networks that underlie the formation of chondrocytes and osteoblasts. Such information is expected to contribute substantially to our basic understanding of skeletal development and remodeling, but will also lead to the identification of novel targets which will serve as new therapeutic avenues for the manipulation of the skeletal cell phenotype.

Publications
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  1. Racacho L, Byrnes AM, MacDonald H, Dranse HJ, Nikkel SM, Allanson J, Rosser E, Underhill TM, Bulman DE. (2015) Two novel-disease causing variants in BMPR1B are associated with brachydactyly type A1. Eur. J. Hum Genet. (in press) – National collaboration [IF 4.3].
  2. Lehnertz B, Pabst C, Su L, Miller M, Liu F, Yi L, Zhang R, Krosl J, Yung E, Kirschner J, Rosten P, Underhill TM, Jin J, Hebert J, Sauvageau G, Humphries RK, Rossi FM. (2014) The methyltransferase G9a regulates HoxA9-dependent transcription in AML. Genes and Development, 28:317-27. [IF 10.8].
  3. Jones KB, Su L, Jin H, Lenz C, Randall RL, Underhill TM, Nielsen TO, Sharma S, Capecchi M. (2013) SS18-SSX2 and the mitochondrial apoptosis pathway in mouse and human synovial sarcomas. Oncogene, 32:2365-71 – International collaboration [IF 8.5].
  4. Chenery A, Burrows K, Antignano F, Underhill TM, Petkovich M, Zaph C. (2013) The retinoic acid-metabolizing enzyme Cyp26b1 regulates CD4 T cell differentiation and function. PLoS One 8(8):e72308. IF 3.7].
  5. Su L, Sampaio AV, Jones KB, Pacheco M, Goytain A, Lin S, Poulin N, Yi L, Rossi FM, Kast J, Capecchi MR, Underhill TM*, Nielsen TO. (2012) Deconstruction of the SS18-SSX fusion oncoprotein complex: Insights into disease etiology and therapeutics. Cancer Cell, 21: 333-47. – International collaboration. [IF 27].
  6. Lemos DR, Paylor B, Chang C, Sampaio A, Underhill TM, Rossi FMV. (2012) Functional convergent white adipogenic progenitors of different lineages participate in a diffused system supporting tissue regeneration. Stem Cells 30:1152-62. [IF 7.8].
  7. Scott A, Sampaio AV, Abraham T, Duronio C, Underhill TM* (2011) Scleraxis expression is coordinately up-regulated in a murine model of patellar tendinopathy. Orthop Res.29:289-296. [IF 1.5].
  8. Sharma A, Abraham T, Sampaio A, Cowan M, Underhill M, Scott A. (2011) Sodium cromolyn reduces expression of CTGF, ADAMTS1, and TIMP3 and modulates post-injury patellar tendon morphology. Orthop. Res. 29:678-83. [IF 1.5].
  9. Scott A, Danielson P, Abraham T, Fong G, Sampaio A, Underhill TM*. (2011) Mechanical force is a physiological determinant of scleraxis expression and tenocyte differentiation. Musculoskeletal Neuronal Interact. 11:124-32. [IF 1.6].
  10. Dranse H, Sampaio AV, Petkovich MP, Underhill TM*. (2011) Genetic deletion of Cyp26b1 negatively impacts limb skeletogenesis by inhibiting chondrogenesis. J Cell Science, 124:2723-2734. – National collaboration [IF 6.3].
  11. Ye M, Berry KM, Asai-Coakwell M, Sundaresan P, Footz T, French CR, Abitbol M, Fleisch VC, Corbett N, Allison WT, Drummond G, Walter MA, Underhill TM, Waskiewicz AJ, Lehmann, OJ. (2010) Mutation of the bone morphogenetic protein GDF3 causes ocular and skeletal anomalies. Human Molecular Genetics 19:287-298. – National collaboration [IF 7.2].
  12. James CG, Stanton LA, Agoston H, Ulici V, Underhill TM, Beier F. (2010) Genome-wide analyses of gene expression during mouse endochondral ossification. PLoS One 13(5):e8693. – National collaboration [IF 4.3].
  13. Karamboulas K, Dranse H, Underhill TM*. (2010) Regulation of BMP-dependent chondrogenesis in early limb mesenchyme by TGFeta signals. Cell Science 123:2068-76. [IF 6.1].
  14. Su L, Cheng H, Sampaio AV, Nielsen TO, Underhill TM*. (2010) EGR1 reactivation by histone deacetylase inhibitors promotes synovial sarcoma cell death through the PTEN tumor suppressor. Oncogene, 29:4352-4361. [IF 7].
  15. Byrnes AM, Racacho L, Nikkel SM, Xiao F, MacDonald H, Underhill TM, Bulman DE. (2010) Mutations in GDF5 presenting a semi-dominant Brachydactyly A1. Human Mutation 31:1155-62. – National collaboration [IF 6.9].
  16. Bragdon B, Thinakaran S, Bonor J, Underhill TM, Petersen NO, Nohe A. (2009) FRET reveals novel protein-receptor interaction of BMP receptors and AP2 at the cell surface. Biophysical Journal 97:1428-35 – International collaboration [IF 4.7].
  17. Widenmaier SB, Sampaio AV, Underhill TM, McIntosh CH*. (2009) Non-canonical activation of Akt/PKB in beta -cells by the incretin hormone glucose-dependent insulinotropic polypeptide (GIP). J. Biol. Chem. 284(16): 10764-73. – Local collaboration [IF 5.5].
  18. Umoh JU, Sampaio AV, Welch I, Pitelka V, Goldberg HA, Underhill TM, Holdsworth DW. (2009) In vivo micro-CT analysis of bone remodeling in a rat calvarial defect model. Med. Biol. 54(7): 2147-61. – National collaboration [IF 2.5].
  19. Welch I, Cowan M, Beier F, Underhill TM*. (2009) The retinoic acid binding protein Crabp2 is increased in murine models of degenerative joint disease. Arthritis Res. Ther. 11(1):R14. – National collaboration [IF 4].
  20. Asai-Coakwell M, French CR, Ye M, Garcha K, Bigot K, Perera AG, Staehling-Hampton K, Mema SC, Chanda B, Mushegian A, Bamforth S, Doschak MR, Li G, Dobbs MB, Giampietro PF, Brooks BP, Vijayalakshmi P, Sauvé Y, Abitbol M, Sundaresan P, Heyningen VV, Pourquié, O, Underhill TM, Waskiewicz AJ, Lehmann OJ. (2009) Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes. Mol. Genet. 18(6):1110-21. – National collaboration [IF 7.8].
  21. Luciani DS, Yang T, Bychkivska Y, Frey MHZ, Jeffrey KD, Kalynyak TB, Sampaio AV, Underhill TM, Johnson JD*. (2009) Roles of IP3R and RyR Ca2+ channels in endoplasmic reticulum stress and -cell death. Diabetes 58:422-32. [IF 8.3].
Further publications can be found here.