Position title: Professor and Chair
Phone: Phone: (608) 262-5491
RESEARCH INTERESTS - Hox genes in mesenchymal stromal cells (MSCs) and their role in development, repair and regeneration
Address: 4405 WIMR II – 1111 Highland Ave. – Madison, WI 53705
Washington University in St. Louis; AB, Biology
University of Wisconsin-Madison, PhD, Biochemistry
(Mentor: Dr. Hector F. DeLuca, PhD)
University of Utah, Department of Human Genetics, Postdoctoral
Fellowship, Salt Lake City, Utah
(Mentor: Dr. Mario R. Capecchi, PhD)
My laboratory use mouse genetics to understand the function of Hox genes during mammalian organogenesis. Hox genes are a highly conserved group of transcriptional regulators that are critical for directing numerous patterning processes during development and that direct repair and regeneration throughout life. The laboratory has investigated many organ systems and current projects focus on the musculoskeletal system and lung. Using primarily advanced mouse genetics, we are dissecting Hox gene function in both development and response to injury and disease. Developmentally, Hox genes are critical for the proper differentiation and integration of cell and tissue types and play key roles in the formation of a functional organ. In response to injury and disease, Hox genes are up-regulated in the same regionally-restricted manner they are employed developmentally, and these genes play important roles in repair and regeneration after tissue damage. Our long-term goal is centered on understanding the downstream mechanisms controlled by Hox genes to direct these developmental and repair processes in mammals and to elucidate how this information can be used to improve potential regenerative therapies in response to injury and disease.
- Apfelbaum AA, Wu F, Magnuson B, Hawkins AG, Jiménez JA, Taylor SD, Pfaltzgraff ER, Song JY, Hall C, Wellik DM, Ljungman M, Furlan S, RJH Ryan, Sarthy JF, Lawlor ER, “Induction of HOXD13 by EWS-FLI1 antagonizes the fusion-dependent transcriptome and regulates neuro-mesenchymal cell state,” in review, eLife.
- Li MH, Marty-Santos L, van Ginkel PR, McDermott AE, Rasky AJ, Lukacs NW, Wellik DM, “The Lung Elastin Matrix Undergoes Rapid Degradation Upon Adult Loss of Hox5 Function”, Frontiers Cell and Developmental Biology, in press.
- Pagani CA, Huber AK, Hwang C, Marini S, Padmanabhan K, Visser N, Yu P, Patel N, Greenstein J, Rasheed H, Nelson R, Kessel K, Vasquez K, Strong AL, Song JY, Wellik DM, Levi B, “Novel lineage tracing system to identify site-specific ectopic bone progenitor cells”, Stem Cell Reports: 16(3): 626-640 (2021).
- Singh P, Banerjee R, Piao S, Costa de Medeiros M, Bellile E, Liu M, Damodaran D, Schmitd LB, Russo N, Danella E, Inglehart RC, Pineault KM, Wellik DM, Wolf G, and D’Silva NJ, “Squamous Cell Carcinoma Subverts Non-cancer Epithelium To Promote Lateral Invasion”, Journal of Experimental Medicine 218(6): 1-21 (2021).
- Garcia PE, Adoumie M, Kim EC, Zhang Y, Scales, MK, El-Tawil YS, Shaikh AZ, Wen H-J, Bednar F, Allen BL, Wellik DM, Crawford, HC, Pasca di Magliano M, “Differential contribution of pancreatic fibroblast subsets to the pasncreatic cancer stroma.”, Cellular and Molecular Gastroenterology and Hepatology 345(20): 30074-6 (2020).
- Hox genes maintain critical roles in the adult skeleton. Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7296-7304. doi: 10.1073/pnas.1920860117. Epub 2020 Mar 13. PubMed PMID: 32170021; PubMed Central PMCID: PMC7132104.
- Pineault KM, Song JY, Kozloff KM, Lucas D, Wellik DM, “Hox11 expressing regional skeletal stem cells are progenitors for osteoblasts, chondrocytes and adipocytes throughout life” , Nat Commun. 2019 Jul 18;10(1):3168. doi: 10.1038/s41467-019-11100-4.
- Hrycaj, S.M., Marty-Santos, L., Cebrian, C., Rasky, A., Ptaschinski, C., Lukacs, N.W., Wellik, D.M., “Hox5 Genes Direct Elastin Network Formation During Alveologenesis By Regulating Myofibroblast Adhesion”, PNAS 115(45): E10605-E10614 (2018).
- Rux, D.R., Song, J.Y., Swinehart, I.T., Pineault, K.M., Schlientz, A.J., Trulik, K.G., Goldstein, S.A., Kozloff, K.M., Lucas, D., Wellik, D.M., “Regionally Restricted Hox Function in Adult Bone Marrow Multipotent Mesenchymal Stem/Stromal Cells,” Developmental Cell 39(6): 653-666 (2016).
- Larsen, B.M., Hrycaj, S.M., Newman, M., Li, Y., Wellik, D.M., “Mesenchymal Hox6 function is required for pancreatic endocrine cell differentiation”, Development 142: 3859-3868 (2015).
- Xu, B., Hyrcaj, S.M., McIntyre, D.M., Takeuchi, J.K., Jeannotte, L., Gaber, Z.B., Novitch, B.G., Wellik, D.M., “Hox5 interacts with Plzf to restrict Shh expression in the developing forelimb”, PNAS 110: 19438-43 (2013).
- Swinehart, I.T., Schlientz, A.J., Quintanilla, C.A., Mortlock, D.P., Wellik, D.M., “Hox11 function is required for regional patterning and integration of muscle, tendon and bone”, Development 140: 4574-82 (2013).
- Xu, B., Wellik, D.M., “Axial Hox9 Activity Establishes the Posterior Compartment in the Developing Forelimb”, PNAS 108: 4888-91 (2011).
- McIntyre, D.C., Rakshit, S, Yallowitz, A. R. Loken. L., Jeannotte, L, Capecchi, M.R., and Wellik, D.M. “Hox Patterning of the Vertebrate Rib Cage”, Development 134: 2981-2989 (2007).
- Wellik, D.M., and Capecchi, M.R. Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. Science 301:363-367 (2003).
- Wellik, D.M., Hawkes, P.J. and Capecchi, M.R. Hox11 paralogous genes are essential for AR0metanephric kidney induction. Genes & Development 16: 1423-1432 (2002).