Associate Professor3901 Rainbow Boulevard
3016 Wahl Hall East
Kansas City, Kansas 66160
Phone: (913) 588-7488
Fax: (913) 588-7430
Email: lheckert@kumc.edu
Ph.D., Washington State University, 1991; Postdoctoral, Case Western Reserve University
One of the most exciting and intriguing problems in biology is the mystery of how and why cells differentiate. All cells start out with the same genetic information, but during embryonic development they "differentiate" into brain cells, muscle cells, cells of different organs, and all of the eventual tissues of the human body. Each of these types of cells has distinguishing characteristics that are determined by the composite of active genes in that cell. The Heckert laboratory is studying the molecular and cellular mechanisms that regulate the differentiation and development of cells involved in sexual development and reproduction.
Currently they are investigating the molecular events involved in activating and regulating genes important for the development and function of the reproductive organs. Of particular interest are the genes responsible for the production of doublesex and mab-3 related transcription factor 1, an evolutionarily conserved protein that is required for testis differentiation, and steroidogenic factor 1, a protein that is required for the formation of adrenal glands and gonads. These proteins, and consequently the genes that are responsible for their production, are critical for proper fetal development and gonad function.
Research in the Heckert laboratory is designed to help solve the mystery surrounding the events important to the production of these proteins and their roles in sex determination. In humans, sex is determined by the presence or absence of the Y chromosome. Individuals with a Y chromosome develop testes, while individuals that lack a Y chromosome develop ovaries. Occasionally the chromosomal makeup of an individual does not correspond to their sex, revealing that a mutation has occurred in a gene critical to either testis or ovarian development. The genes we are studying are implicated in XY sex reversal. Their studies seek to understand how these genes are responsible for this abnormality and will provide a greater understanding of the processes directing cell-specific gene expression, gonad development, and sex determination.
Daggett MAF, Rice DA, Heckert LL (2000) Expression of steroidogenic factor 1 in the testis requires an E box and CCAAT box in its promoter proximal region. Biol Reprod 62, 670-679.
Chen J-K, Heckert LL (2001) DMRT1 expression is regulated by follicle-stimulating hormone and phorbol esters in postnatal Sertoli cells. Endocrinology 142, 1167-1178.
Heckert LL (2001) Activation of the rat FSHR promoter by steroidogenic factor 1 is blocked by PKA and requires USF binding to a proximal E-box element. Mol Endocrinol 15, 704-715.
Lei N, Heckert LL (2002) Sp1 and Egr1 regulate transcription of the Dmrt1 gene in Sertoli cells. Biol Reprod 66, 675-684.
Scherrer, S.P., Rice, D.A. and Heckert, L.L. (2002) “Expression of steroidogenic factor 1 in the testis requires an interactive array of elements within its proximal promoter” Biology of Reproduction 67, 1509-1521
Lei, N. and Heckert, LL (2004) Gata4 regulates testis expression of Dmrt1. Mol. Cell Biol. 24, 377-388.
Heckert L. and Hermann B. (2004) “Transcriptional regulation of the FSH receptor in testes” Proceedings of the 12th Congress of the International Society of Endocrinology. in press
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The University of Kansas Medical Center