RESEARCH SUMMARY
I have always been fascinated with pattern formation, specifically the role that transcription factors play in orchestrating the formation of structures and tissues through the regulation of their downstream targets. Early in my career, I was lucky to examine these concepts in the Mexican axolotl, a paedomorphic salamander with incredible regeneration potential, through embryonic tissue grafts and the cloning and identification of transcription factors involved in the formation of the head cartilage. I then moved on to study the regulation of Hox genes in the development of the mouse nervous system. First, in Mark Featherstone’s laboratory where I studied the mechanism of retinoic acid response elements (RAREs) in setting the anterior boundaries of Hox gene expression in the embryonic head, and then in Robb Krumlauf’s laboratory where I characterized shadow enhancers and a potential boundary element that contributed to the expression pattern of HoxB genes in the developing gut, heart and neural tube. In Robb’s lab, my interest in evo-dev developed where Hox regulatory regions were demonstrated to be functionally conserved between mouse, zebrafish, chicken, and lamprey. Working with Cnidarians, I will be examining similar regulatory pathways in defining and patterning the anatomical features of these animals and characterizing ancestral genetic modules that were established early in the development of the metazoans.
EDUCATION
Ph.D. (Experimental Medicine), 2002, McGill University, Montreal, Quebec, Canada.
Dissertation title: “The role of a retinoic acid response element in setting the anterior border of Hoxd4 expression in the developing hindbrain”
Advisor: Mark Featherstone
M.Sc. (Biology), 1996, University of Ottawa, Ottawa, Ontario, Canada.
Dissertation title: “Cloning msx and dlx homeobox-containing genes from the Mexican axolotl (Ambystoma mexicanum)”
Advisor: Marc Ekker and John Armstrong
B.Sc. (Honors) with Biotechnology Option, 1994, University of Ottawa, Ottawa, Ontario, Canada. Honors Project title: “Cranial neural crest cell identity is pre-programmed prior to migration in the Mexican axolotl embryo”
Advisor: John Armstrong
SELECTED PUBLICATIONS
Afzal, Z., Lange, J., Nolte, C., McKinney, S., Wood, C., Paulson, A., De Kumar, B., Unruh, J., Slaughter, B. D., and Krumlauf, R. (2023).
Shared Retinoic Acid Response Enhancers Coordinately Regulate Nascent Transcription of Hoxb Coding and Non-coding RNAs in the Developing Mouse Neural Tube. Development 150 (10).
Qian, P., De Kumar, B., He, Xi C., Nolte, C., Gogol, Madelaine, Ahn, Y., Chen, S., Li, Z., Xu, H., Perry, J. M., Hu, D., Tao, F., Zhao, M., Han, Y., Hall, D., Peak, A., Paulson, A., Zhao, C., Vendatraman, A., Box, A., Perera, A., Haug, J.S., Parmely, T., Li, H., Krumlauf, R., and Li, L. (2018).
Retinoid-Sensitive Epigenetic Regulation of the Hoxb Cluster Maintains Normal Hematopoiesis and Inhibits Leukemogenesis. Cell Stem Cell 22(5), p740-754.e7
Nolte, C., Jinks, T., Wang, X., Martinez Pastor, M. T., and Krumlauf, R. (2013).
“Shadow Enhancers Flanking the HoxB Cluster Direct Dynamic Hox Expression in Early Heart and Endoderm Development.” Dev. Biol. 383, 158-173.