Leanne M Wiedemann, PhD

The primary objective of my research is to understand the function of genes altered as a result of tumor-associated chromosomal translocations, both their normal function and defining their role in the oncogenic process. Following our lab’s molecular characterization of the MLL locus and chromosomal translocations, in light of MLL’s critical role in leukemogenesis, we have begun to define both the normal and oncogenic mechanisms of action and down stream targets. Both trx in Drosophila and MLL (in rodent and human) gene products are known to play key roles in the regulation of Hox genes. Hox genes themselves have been implicated in the oncogenic processes in the hematopoietic system; therefore, it is important to define the cis and trans-regulatory pathways which regulate this gene family as well as their downstream targets. The Stowers Institute provides a rich collaborative environment to explore the roles of MLL in Hox gene regulation and oncogenesis: in the context of spatial and temporal patterning in development.

Appointments:           

Research Degree Coordinator
Stowers Institute for Medical Research                                                      2006- present

Staff Scientist

Stowers Institute for Medical Research                                                      2000- present

Professor

Department of Pathology and Laboratory Medicine,
Division of Cancer & Developmental Biology,
School of Medicine, University of Kansas Medical Center                           2009- present

Affiliate Member of the Kansas Masonic Cancer Research Institute            2005- present

Recent Publications

Tümpel, S., Wiedemann, L.M., and Krumlauf, R. (2009). Hox genes and segmentation of the vertebrate hindbrain. In HOX Genes, O. Pourquié, ed. (Burlington, Academic Press), pp. 103-137.

Tümpel, S, Cambronero, F, Sims, C, Krumlauf, R, Wiedemann, LM (2008) A regulatory module embedded in the coding region of Hoxa2 controls expression in rhombomere 2. Proc. Natl. Acad. Sci., U S A: 105, 20077-20082.

Tümpel S, Cambronero F, Ferretti E, Blasi F, Wiedemann LM, Krumlauf R. (2007) Expression of Hoxa2 in rhombomere 4 is regulated by a conserved cross-regulatory mechanism dependent upon Hoxb1. Dev. Biol. 302: 646-60.

He XC, Yin T, Grindley JC, Tian Q, Sato T, Tao WA, Dirisina R, Porter-Westpfahl KS, Hembree M, Johnson T, Wiedemann LM, Barrett TA, Hood L, Wu H, Li L. (2007) PTEN-deficient intestinal stem cells initiate intestinal polyposis. Nat. Genet. 39: 189-98.

Zhang J, He XC, Tong WG, Johnson T, Wiedemann LM, Mishina Y, Feng JQ, Li L. (2006) BMP signaling inhibits hair follicle anagen induction by restricting epithelial stem/progenitor cell activation and expansion. Stem Cells 25: 2826-2839.

Zhang J, Grindley JC, Yin T, Jayasinghe S, He XC, Ross JT, Haug JS, Rupp D, Porter-Westpfahl KS, Wiedemann LM, Wu H, Li L (2006) PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention. Nature 441, 518-522.

Tümpel, S, Cambronero, F, Wiedemann, LM, Krumlauf, R (2006) Evolution of cis elements in the differential expression of two Hoxa2 coparalogous genes in pufferfish (Takifugu rubripes). Proc. Natl. Acad. Sci., U S A 103, 5419-5424

Ferretti, E, Cambronero, F, Tümpel, S, Longobardi, E, Wiedemann, LM, Blasi, F, Krumlauf, R (2005). The Hoxb1 enhancer and control of rhombomere 4 expression: Complex interplay between PREP1-PBX1-HOXB1 binding sites. Mol. Cell. Biol. 25, 8541-52

Serpente, P., Tümpel, S., Ghyselinck, N. B., Niederreither, K., Wiedemann, L. M., Dollé, P., Chambon, P., Krumlauf, R., and Gould, A. P. (2005). Direct crossregulation between retinoic acid receptor b and Hox genes during hindbrain segmentation. Development 132, 503-513

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He, X. C., Zhang, J., Tong, W.-G., Tawfik, O., Ross, J., Scoville, D. H., Tian, Q., Zeng, X., He, X., Wiedemann, L. M., Mishina, Y., and Li, L. (2004). BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt–b-catenin signaling. Nat Gen 36, 1117-1121.

Zhang, J., Niu, C., Ye, L., Huang, H., He, X., Tong, W.-G., Ross, J., Haug, J., Johnson, T., Feng, J. Q., Harris, S., Wiedemann, L. M., Mishina, Y., and Li, L. (2003). Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425, 836-841.

Wiedemann, L. M., and Greaves, M. F. (2002). Biology of leukaemia. In Oxford Textbook of Oncology, R. L. Souhami, I. Tannock, P. Hohenberger, and J.-C. Haoriot, eds. (New York, Oxford University Press), pp. 2183-2190.

Tümpel, S., Maconochie, M., Wiedemann, L. M., and Krumlauf, R. (2002). Conservation and diversity in the cis-regulatory networks that integrate information controlling expression of Hoxa2 in hindbrain and cranial neural crest cells in vertebrates. Dev. Biol. 246, 45-56.

Schulte, C. E., von Lindern, M., Steinlein, P., Beug, H., and Wiedemann, L. M. (2002). MLL-ENL cooperates with SCF to transform primary avian multipotent cells. EMBO J 21, 4297-4306.

So, C.-W., Sham, M. H., Chew, S. L., Cheung, N., Chung, S. K., Caldas, C., Wiedemann, L. M., and Chan, L. C. (2000). Expression and protein-binding studies of the EEN gene family, new interacting partners for dynamin, synaptojanin and huntingtin proteins. Biochem J 348, 447-458.
  

Guidez, F., Petrie, K., Ford, A. M., Lu, H., Bennett, C. A., MacGregor, A., Hannemann, J., Ito, Y., Ghysdael, J., Greaves, M., Wiedemann, L. M., and Zelent, A. (2000). Recruitment of the nuclear receptor corepressor N-CoR by the TEL moiety of the childhood leukemia-associated TEL-AML1 oncoprotein. Blood 96, 2557-2561.
  

Kim-Rouille, M.-H., MacGregor, A., Wiedemann, L. M., Greaves, M. F., and Navarrete, C. (1999). MLL-AF4 gene fusions in normal newborns. Blood 93, 1107-1108.

Hannemann, J., Healy, L. E., Ridge, S. A., and Wiedemann, L. M. (1998). The second ETV6 allele is not necessarily deleted in acute leukemias with a ETV6/ABL fusion. Genes Chrom Can 21, 256-259.

Caldas, C., Kim, M.-H., MacGregor, A., Cain, D., Aparicio, S., and Wiedemann, L. M. (1998). Isolation and characterization of a pufferfish MLL (mixed lineage leukemia) like gene (fMLL) reveals evolutionary conservation in vertebrate genes related to Drosophila trithorax. Oncogene 16, 3233-3241.