Leanne M Wiedemann, PhD

The primary objective of my research is the identification and characterisation of genes altered as a result of chromosomal translocations and the determination of their role in leukemogenesis. In order to achieve this, we utilize in vivo and in vitro model systems. We incorporate comparative genomic analyses, RNA and protein analysis and look forward to moving into microarray technologies. Information deduced from our studies is also used to design molecular methodologies, which will assist in diagnosis and management of leukaemia and lymphoma. We focus on the molecular events that occur in leukemias with translocations involving the MLL gene, a gene normally involved in the regulation of HOX genes. In our efforts to understand the altered role of these proteins in leukemogenesis, we need to explore their normal function as well.  This has developed into additional projects describing the regulatory mechanism controlling candidate genes downstream of the affected proteins, particularly the HOX genes.

Appointments:           
Staff Scientist
Stowers Institute for Medical Research                                                      2000- present

Associate Professor,

Department of Pathology and Laboratory Medicine,
Division of Cancer & Developmental Biology,
School of Medicine, University of Kansas Medical Center                           2001- present

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

Recent Publications

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.