Deneen Wellik, Ph.D.
Deneen M. Wellik, PhD, is a Professor in Molecular Medicine & Genetics and is jointly appointed in the Department of Cell & Developmental Biology. She is the Director for the Center for Organogenesis at the University of Michigan and serves as the Director of the Training Grant in Organogenesis. She currently serves as an instructor at Cold Spring Harbor on Mouse Development, Stem Cells and Cancer, and is also a member of the NIH DEV1 study section.
Hox genes are a highly conserved set of genes that are key regulators of animal development. Numerous organogenesis defects are observed with loss-of-function mutations in this gene family. In order to elucidate the basic mechanisms of Hox function during mammalian organogenesis and development, we employ mouse developmental genetics, molecular biology and biochemical approaches. The laboratory focuses on several model organ systems including the musculoskeletal system, the developing limb, pancreas, gut and urogenital development to dissect how Hox genes function to pattern tissue types during organogenesis and integrate these cell types to form a functional organ. These studies will contribute to our long-term goal of understanding the general downstream mechanisms controlled by Hox genes to direct differentiation and development processes in mammals and to elucidate how this information can be used to improve potential regenerative therapies for affected organ systems.
A central goal in the laboratory is dissecting the role of Hox genes in limb patterning, musculoskeletal development as well as musuculoskeletal tissue repair after injury. Using null, conditional loss-of function and reporter fusion alleles, we have identified and reported many defects in limb development associated with loss of Hox function. Specifically, we are pursuing early patterning defects in these mutants, as well as investigating the mechanism by which these genes direct the integration of muscle, tendon and skeletal tissue, and exploring how these genes are re-employed after injury to regulate musculoskeletal repair and healing process.
Other projects in the laboratory focus on understanding the role of Hox genes in endodermal organogenesis. Hox genes are expressed with anteroposterior specific boundaries during endodermal development and these expression patterns are maintained through adulthood. We are exploring the defects along this axis developmentally and the mechanisms of Hox function in these tissues, as well as how these genes are redeployed and function in response to injury and disease.
|1986||A.B., Washington University St. Louis (Biology)|
|1995||Ph.D., University of Wisconsin, Madison (Biochemistry, Dr. Hector F. DeLuca)|
|1996-2002||Postdoctoral Fellow, University of Utah (Dr. Mario Capecchi)|
Rux DR, Song JY, Swinehart IT, Pineault KM, Schlientz AJ, Trulik KG, Goldstein SA, Kozloff KM, Lucas D, Wellik DM. Regionally Restricted Hox Function in Adult Bone Marrow Multipotent Mesenchymal Stem/Stromal Cells. Developmental Cell. 2016; 39(6):653-666. NIHMS830581; PMID27939685
Larsen BM, Hrycaj SM, Newman M, Li Y, Wellik DM. Mesenchymal Hox6 function is required for mouse pancreatic endocrine cell differentiation. Development. 2015; Nov 15;142(22):3859-68. PMC4712882
Pineault KM, Swinehart IT, Garthus KN, Ho E, Yao Q, Schipani E, Kozloff KM, Wellik DM. Hox11 genes regulate postnatal longitudinal bone growth and growth plate proliferation.Biology Open. 2015; 4(11):1538-48. PMC4728342
Hrycaj SM, Dye BR, Baker NC, Larsen BM, Burke AC, Spence JR, Wellik DM. Hox5 Genes Regulate the Wnt2/2b-Bmp4-Signaling Axis during Lung Development. Cell Reports 2015;12(6):903-12. PMC4536095
Xu B, Hyrcaj SM, McIntyre DM, Takeuchi JK, Jeannotte L, Gaber ZB, Novitch BG, Wellik DM. Hox5 interacts with Plzf to restrict Shh expression in the developing forelimb. Proc Natl Acad Sci USA 2013; 110(48): 19438-43. PMC3845161
Swinehart IT, Schlientz AJ, Quintanilla CA, Mortlock DP, Wellik DM. Hox11 genes are required for regional patterning and integration of muscle, tendon and bone. Development, 2013; 140:4574-82. PMC3817943
Xu B, Hariharan A, Rakshit S, Dressier GR, Wellik DM. The role of Pax2 in mouse prostate development. Prostate, 2012; 72(2):217-224. PMC3178747.
Yallowitz AR, Hrycaj SM, Short KM, Smyth IM, Wellik DM. Hox10 genes function in kidney development in the differentiation and integration of the cortical stroma. PLoS One, 2011; 6(8):e23410. PMC3156768.
Xu B, Wellik DM. Axial Hox9 activity establishes the posterior field in the developing forelimb. Proc Natl Acad Sci USA, 2011; 108(12):4888-4891. PMC3064354.
Nelson LT, Rakshit S, Sun H, Wellik DM. Generation and expression of a Hoxa11eGFP targeted allele in mice. Developmental Dynamics 2008; 237(11):3410-3416. PMC2855819.
Gong KQ, Yallowitz AR, Sun H, Dressler GR, Wellik DM. A Hox-Eya-Pax complex regulates early kidney developmental gene expression. Mol Cell Biology, 2007; 27(21):7661-7668. PMC2169072.
McIntyre DC, Rakshit S, Yallowitz AR, Loken L, Jeannotte L, Capecchi MR, Wellik DM. Hox patterning of the vertebrate rib cage. Development, 2007; 134(16):2981-2989. PMID17626057
Wellik DM, Capecchi MR. Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. Science, 2003; 301(5631):363-367. PMID12869760.
Wellik DM, Hawkes PJ, Capecchi MR. Hox11 paralogous genes are essential for metanephric kidney induction. Genes Dev, 2002; 16(11):1423-1432. PMC 186320.
Updated Jan 2017