Leanne Wiedemann

Leanne Wiedemann
Staff Scientist
Research Degree Coordinator, Open University
 

Professor, Department of Pathology and Laboratory Medicine,
   The University of Kansas School of Medicine


lmw@stowers.org
816.926.4052



Research Summary

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.


Selected Publications

McEllin JA, Alexander TB, Tumpel S, Wiedemann LM, Krumlauf R. Analyses of fugu hoxa2 genes provide evidence for subfunctionalization of neural crest cell and rhombomere cis-regulatory modules during vertebrate evolution. Dev Biol.2016;409:530-542. Abstract

Smith JJ, Kuraku S, Holt C, Sauka-Spengler T, Jiang N, Campbell MS, Yandell MD, Manousaki T, Meyer A, Bloom OE, Morgan JR, Buxbaum JD, Sachidanandam R, Sims C, Garruss AS, Cook M, Krumlauf R, Wiedemann LM, Sower SA, Decatur WA, Hall JA, Amemiya CT, Saha NR, Buckley KM, Rast JP, Das S, Hirano M, McCurley N, Guo P, Rohner N, Tabin CJ, Piccinelli P, Elgar G, Ruffier M, Aken BL, Searle SM, Muffato M, Pignatelli M, Herrero J, Jones M, Brown CT, Chung-Davidson YW, Nanlohy KG, Libants SV, Yeh CY, McCauley DW, Langeland JA, Pancer Z, Fritzsch B, de Jong PJ, Zhu B, Fulton LL, Theising B, Flicek P, Bronner ME, Warren WC, Clifton SW, Wilson RK, Li W. Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution. Nat Genet.2013;45:415-421, 421e411-412. Abstract

Wang P, Lin C, Smith ER, Guo H, Sanderson BW, Wu M, Gogol M, Alexander T, Seidel C, Wiedemann LM, Ge K, Krumlauf R, Shilatifard A. (2009). Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II. Molecular and cellular biology29, 6074-6085. Abstract

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

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. Abstract

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. Abstract

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. Abstract

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. Abstract

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. Abstract

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. Abstract

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

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

He XC, Zhang J, Tong WG, Tawfik O, Ross J, Scoville DH, Tian Q, Zeng X, He X, Wiedemann LM, Mishina Y, Li L. (2004). BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt–b-catenin signaling. Nat Gen 36, 1117-1121. Abstract

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

Wiedemann LM, Greaves MF. (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,LM, 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. Abstract

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

So CW, Sham MH, Chew SL, Cheung N, Chung SK, Caldas C, Wiedemann LM, Chan LC. (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 AM, Lu H, Bennett CA, MacGregor A, Hannemann J, Ito Y, Ghysdael J, Greaves M, Wiedemann LM, 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 MH, MacGregor A, Wiedemann LM, Greaves MF, Navarrete C. (1999). MLL-AF4 gene fusions in normal newborns. Blood 93, 1107-1108.

Hannemann J, Healy LE, Ridge SA, Wiedemann  LM. (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 MH, MacGregor A, Cain D, Aparicio S, Wiedemann LM. (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.