Dr. John Cobb
Positions
Child Health & Wellness Researcher
Alberta Children's Hospital Research Institute
Contact information
Phone number
Office: +1 (403) 220-3554
Background
Educational Background
B.A. Honors Program in Liberal Arts, University of Tennesee, 1986
Doctor of Philosophy Biochemistry, Cellular and Molecular Biology, University of Tennesee, 1998
Research
Areas of Research
Different transcription factors are necessary for the development of specific segments of the limbs, and birth defects can result when the function of a transcription factor is missing. For example, we have found that the mouse gene Shox2 is necessary to form the proximal segment of the limbs (the humerus in the arms and the femur in the legs). Shox2 is closely related to a human gene called SHOX whose disruption causes the malformed limbs in people with Turner, Léri-Weill and Langer syndromes, which together affect approximately 1 in 1,000 people. Patients with these syndromes all have a characteristic shortening in the middle portion of the limbs, the radius/ulna of the arms and the tibia/fibula of the legs. Therefore, both human SHOX patients and Shox2-mutant mice develop with shortened limbs, although the phenotypes are restricted to different segments of the limbs. We hypothesize that mouse Shox2 and human SHOX have similar cellular functions that are exerted in different parts of the embryo according to where the genes are expressed. Therefore, we are studying how Shox2 controls limb development as a model for human SHOX function. We also study how these genes are regulated since SHOX-deficient phenotypes can be caused by deletions that leave the coding sequence of the SHOX gene intact. These deletions most likely remove regulatory elements called enhancers-DNA sequences that control the expression of genes in specific tissues during development. However, since these effects occur in humans, direct demonstration of this function is difficult. We have produced transgenic mice that directly test whether specific sequences near Shox genes (human SHOX and mouse Shox2) mediate enhancer activity. Most notably, we have used our transgenic mouse assay to demonstrate the limb-specific activity of a human enhancer from a region frequently deleted in SHOX patients. We are expanding on this finding with the goal of gaining a comprehensive understanding of how expression of the SHOX gene is regulated.
Participation in university strategic initiatives
Courses
| Course number | Course title | Semester |
|---|---|---|
| BIOL 601.03 | Integrative Cell Biology I | Fall 2022 |
| CMMB 403 | Developmental Biology of Animals | Fall 2022 |
| CMMB 528A | Research Project in Cellular, Molecular and Microbial Biology | Fall 2022 |
| BIOL 601.04 | Integrative Cell Biology II | Winter 2023 |
| CMMB 505 | Advanced Developmental Biology | Winter 2023 |
Publications
- Characterization of the regulatory landscape governing Shox2 expression in the mouse limb. John Andrew Cobb; Eddie Rodriguez-Carballo; Samuel Abassah-Oppong; Anja Ljubojevic. (2017)
- Identifying novel functions of Shox2 within the developing murine hindbrain. Lily Han; Greg Hamilton; Dragana Dokic; John Andrew Cobb; Saveen Sidhoo; Isabella Skuplik. (2018)
- The characterization of a novel limb enhancer of the human SHOX gene. Brent Bobick; John Andrew Cobb; Jessica M. Rosin; Isabella Skuplik. (2018)
- Evolutionary sequence conservation in the identification of enhancers that regulate short-stature homeobox (Shox) gene expression during limb development in humans and mice. Eddie Rodriguez-Carballo; John Andrew Cobb; Anja Ljubojevic; Isabella Skuplik; Samuel Abassah-Oppong. (2017)
- The characterization of a novel limb enhancer of the human SHOX gene. Brent Bobick; Isabella Skuplik; John Andrew Cobb; Jessica M. Rosin. (2017)
More Information
Publications
- Jessica M Rosin, Deborah M Kurrasch and John Cobb. (2015) Shox2 is required for the proper development of the facial motor nucleus and the establishment of the facial nerves. BMC Neuroscience. 16:39 doi:10.1186/s12868-015-0176-0.
- Rosin, Jessica M.; McAllister Brendan B; Dyck, Richard H.; Percival, Christopher J,; Kurrasch Deborah, M.; Cobb, John. (2014) Mice lacking the transcription factor SHOX2 display impaired cerebellar development and deficits in motor coordination. Developmental Biology. doi: 10.1016/j.yd- bio.2014.12.013.
- Rosin, J.M.; Abassah-Oppong, S.; Cobb, J. (2013) Comparative transgenic analysis of enhancers from the human SHOX and mouse Shox2 genomic regions. Human Molecular Genetics. Epub ahead of print, doi: 10.1093/hmg/ddt163.
- Bobick, B.E.; Cobb, J. (2012) Shox2 regulates progression through chondrogenesis in the mouse proximal limb. Journal of Cell Science. 125: 6071-6083.
- Neufeld S.; Rosin J.M.; Ambasta A.; Hui K.; Shaneman V.; Crowder R.; Vickerman L.; Cobb J. (2012) A conditional allele of Rspo3 reveals redundant function of R-spondins during mouse limb development. Genesis. 50: 741-749.
- Scott, A.; Hasegawa, H.; Sakurai, K.; Yaron, A.; Cobb, J.; Wang, F. (2011) Transcription factor short stature homeobox 2 is required for proper development of tropomyosin-related kinase B-expressing mechanosensory neurons. Journal of Neuroscience. 31: 6741-6749.
- Vickerman L, Neufeld S, Cobb J. (2010) Shox2 function couples neural, muscular and skeletal development in the proximal forelimb. Dev Biol. 2011 Feb 15;350(2):323-36. Epub 2010 Dec 13.
- Cobb, J.; Dierich, A.; Huss-Garcia, Y.; Duboule D. (2006) A mouse model for human short stature syndromes identifies Shox2 as an upstream regulator of Runx2 during long bone development. Proceedings of the National Academy of Sciences, USA 103: 4511-4515.
- Cobb, J.; Duboule, D. (2005) Comparative analysis of genes downstream of the Hoxd cluster in developing digits and external genitalia. Development 132: 3055-67.
- Eaker, S.; Cobb, J.; Pyle, A.; Handel, M. A. (2002) Meiotic prophase abnormalities and metaphase cell death in MLH1-deficient mouse spermatocytes: insights into regulation of spermatogenic progress. Developmental Biology 249: 85-95.
- Libby, B. J.; De La Fuente, R.; O'Brien, M. J.; Wigglesworth, K.; Cobb, J., Inselman, A.; Eaker, S.; Handel, M. A.; Eppig, J. J.; Schimenti, J. C. (2002) The mouse meiotic mutation mei1 disrupts chromosome synapsis with sexually dimorphic consequences for meiotic progression. Developmental Biology 242: 174-87.
- Eaker, S.; Pyle, A.; Cobb, J.; Handel, M. A. (2001) Evidence for meiotic spindle checkpoint from analysis of spermatocytes from Robertsonian-chromosome heterozygous mice. Journal of Cell Science 114: 2953-65
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