NAME
Leslie L. Heckert

POSITION TITLE
Principal Investigator

EDUCATION/TRAINING

University of Montana, Missoula, MT

B.A

1982

Chemistry

University of Montana, Missoula, MT

M.S.

1986

Biochemistry

Washington State University, Pullman, WA

Ph.D.

1991

Biochemistry

Professional Experience

1987-1991

Research Assistant, Dept of Biochem. & Biophys., Washington State Univ., Pullman, WA

1991-1992

Post doctoral Research Associate, Dept of Biochem. & Biophys., Wash. State Univ.,
Pullman, WA

1992-1996

Post doctoral Research Associate, Dept. of Pharmacology, Case Western Res. Univ., Cleveland, OH

1996-present

Assistant Professor, Dept. of Mol.& Int Phys, University of Kansas Medical Center, Kansas City, KS

Awards and Other Professional Activities:

1981

Watkin's Research Scholarship, University of Montana

1982

Samuel and Nelly Sinclair Maclay Memorial Award, student excellence award, University of Montana

1991

Harriett B. Rigas Award, for outstanding graduate studies, Washington State University

1993

Postdoctoral Fellow, Neuroscience Training Grant, Case Western Reserve University

1993-1996

NIH Postdoctoral Fellow, National Research Service Award, Case Western Reserve University

1999

Biochemical Endocrinology Study Section (ad hoc), NIH

1999

Investigator Research Award, University of Kansas Medical Center
2000-2002 Self Faculty Scholar Award for research and mentoring, University of Kansas

Research Projects Ongoing or Completed During the Last Three Years

"Transcriptional Regulation of the FSH Receptor"
Principal Investigator: Leslie L. Heckert, Ph.D.
Agency: NIH-NICHD
Type: Active R29 (HD35217-01A1, 01/01/98-12/31/2002)
The long term goal of this project is to characterize the transcriptional mechanisms that determine cell-specific expression and regulation of the FSH receptor gene. The project focuses on the identification of important responsive elements located in the FSHR gene that are needed for promoter function and the characterization of the proteins that bind these elements.

"Center for Reproductive Sciences"
Principal Investigator: Paul Terranova, Ph.D.
Agency: NIH/NICHD
Type: Active P30 HD33994-03 (04/01/96-03/30/00)
This is a center grant in reproductive sciences. There are five divisions within the center: administrative, cell and tissue culture, imaging and photography, transgenic, and new program development. I am the investigator for the new program development. The main focus of this project is to develop a PCR based strategy to clone HLH proteins. The project period is from 04/01/98 to 03/30/01.

"Regulation of SF-1 in the gonads"
Principal Investigator: Leslie L. Heckert
Agency: NIH/NICHD
Type: Active; R01 HD38498-01 (4/10/00-3/31/05)
The focus of this project is to identify the transcriptional mechanisms that direct expression of the orphan nuclear receptor steroidogenic factor 1 in Sertoli and Leydig cells of the testis. The main goals are to identify and characterize the transcription factors that regulate this gene and determine their physiological roles in the testis.

"Hormonal & cell-specific regulation of Dmrt1"
Principal Investigator: Leslie Heckert
Agency: NIH/NICHD
Type: Pending R01HD41065 (04/02-03/07 )
One goal of this project is to determine the means by which Dmrt1 is transcribed in the testis and how its transcription is controlled by the hormone FSH. In addition, we aim to determine a high-affinity DNA binding site for Dmrt1and identify specific Dmrt1 target genes in the testes. This project is currently being funded through the SELF Graduate Fellowship program at The University of Kansas and the Research Institute at The University of Kansas Medical Center.

"SF-1 & CREB: Gonadal Roles by a New Transgenic Approach."
Principal Investigator: Leslie L. Heckert, Ph.D.
Agency: NIH-NICHD
Type: Inactive R03 (HD35871-01, 01/01/1998-12/31/99)
The goal of this project is to develop transgenic mouse models that over-express either SF-1 or CREB in
testicular Sertoli cells. This project also involves testing a new method that uses cre recombinase to induce
over-expression in a cell-specific manner.

Bibliography:

1. Heckert, L.L., Butler, M.H., Reimers, J.M., Albe, K.R., and Wright, B.E. (1989) Purification and characterization of the 2-oxoglutarate dehydrogenase complex from Dictyostelium discoideum. J. Gen. Microbiol. 135:155-161.

2. Griswold, M.D., Heckert, L.L., Karl, A.F., Law, L., Roberts, K., Siiteri, J., Stallard, B., Tsuruta, J. and Sylvester, S.R. (1989) Sertoli cell secreted proteins in normal and synchronized testes. Development and Function of the Reproductive Organs, Serono Symposia Review No. 21, pp 207-218.

3. Zheng, W., Butwell, T.J., Heckert, L., Griswold, M.D. and Bellve, A.R. (1990) Pleiotropic actions of seminiferous growth factors on two testicular cell lines. Comparison with acidic and basic fibroblast growth factors. Growth Factors 3:73-82

4. Heckert, L. and Griswold, M.D. (1991) The changing fucntion of follicle-stimulating hormone in the testes of prenatal, newborn, immature,and adult rats. In: Follicle Stimulating Hormone (M. Hunzicker-Dunn and N. Schwartz, eds) Springer-Verlag, N.Y. pp 237-245.

5. Heckert, L.L. and Griswold, M.D. (1991) Expression of FSH receptor in rat testes and Sertoli cells. Mol. Endocrinol. 5:670-677.

6. Linder, C.C., Heckert, L.L., Roberts, K.P., Kim, K.H., and Griswold, M.D. (1991) Expression of receptors during the cycle of the seminiferous epithelium. New York Academy of Science 63:313-321

7. Heckert, L.L., Daley I.J., and Griswold, M.D. (1992) Structural organization of the follicle-stimulating hormone receptor gene. Mol. Endocrinol. 6:70-80

8. Heckert, L and Griswold M.D. (1993) Expression of the FSH receptor in the testis. Recent Progress in Hormone Research 48:61-77.

9. Clay, C.M., Keri, R.A., Finicle, A.B., Heckert, L.L., Hamernik, D.L., Marschke, K.M., Wilson, E.M., French, F.S., and Nilson, J.H. (1993) Transcriptional Repression of the Glycoprotein Hormone *-Subunit Gene by Androgen may Involve Direct Binding of Androgen Receptor to the Proximal Promoter. J. Biol. Chem. 268, 13556-13564.

10. Griswold, M.D., Heckert, L.L., Goetz, T., and Linder C.C. (1994) Expression of the FSHR in the Sertoli cell. In: Function of Somatic Cells in the Testis. (A. Barke Ed.) Serono Symposium Springer-Verlag, New York, pp.233-244.

11. Clay, C.M., Keri, R.A., Hamernik, D.L., Heckert, L.L., and Nilson, J.H. 1994. Endocrine regulation of glycoprotein hormone alpha subunit gene expression in transgenic mice. in Glycoprotein hormones: Structure, function and clinical implications, ed. J.W. Lustbader, D. Puett, and R.W. Ruddon, Raven Press, Serono Symposia, USA.

12. McGuinness, M.P., Linder, C.C., Morales, C.R., Heckert, L.L., Pikus, J., and Griswold, M.D. (1994). Relationship of a mouse Sertoli cell line (MSC-1) to normal Sertoli cells. Biol. Reprod. 51:116-124.

13. Linder, C., Heckert, L., Goetz, T., and Griswold, M.D. (1994). Follicle-stimulating hormone receptor gene promoter activity. Endocrine 2:957-966.

14. Griswold, M.D., Heckert, L.L., Goetz, T.L., and Linder,C.C. (1994). Structural and functional characterization of the FSHR gene. In: Cell and Molecular Biology of the Testis. (M. Dufoe, A. Fabbri and A. Isidor, Eds.) Frontiers in Endocrinology Series, vol. 5, Ares-Serono Publications, Rome. pp.61-68.

15. Griswold, M.D., and Heckert, L.L. (1994). Regulation of expression of FSHR. In: Ovarian cell Interactions. (A. Hsueh and D. Schombert eds.) Springer-Verlag, New York. pp.100-109.

16. Griswold, M.D., Heckert, L.L., and Linder, C. (1995) The molecular biology of the FSH receptor. J. Steroid Biochem and Mol. Biol. 53:215-218.

17. Heckert, L.L., Schultz, K., and Nilson, J.H. (1995). Different composite regulatory elements direct expression of the human a subunit gene to pituitary and placenta. J. Biol. Chem. 270, 26497-26504

18. Heckert, L.L., Schultz, K., and Nilson, J.H. (1996) The cAMP response elements of the a subunit gene bind similar proteins in trophoblasts and gonadotropes but have distinct functional sequence requirements. J. Biol. Chem. 271:31650-31656

19. Heckert, L.L., Wilson, E.M., and Nilson, J.H. (1997) Transcriptional repression of the a subunit gene by androgen receptor occurs independently of DNA binding but requires the DNA-binding and ligand-binding domains of the receptor. Mol. Endocrinol. 11: 1497-1506

20. Heckert, L.L., Daggett, M.A.F., and Chen, J. (1998) Multiple promoter elements contribute to activity of the FSHR gene in testicular Sertoli cells. Mol. Endocrinol. 12:1499-1512

21. Melissa A.F. Daggett, Rice DA, and Heckert L.L. (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

22. Heckert, L.L., Sawadogo, M., Daggett, M.A.F., and Chen, J. (2000) "The USF proteins regulate transcription of the follicle-stimulating hormone receptor but are insufficient for cell-specific expression." Mol. Endocrinol 14: 1836-1848.

23. Chen J-K and Heckert LL (2001) "DMRT1 expression is regulated by follicle-stimulating hormone and phorbol esters in postnatal Sertoli cells". Endocrinology 142:1167-1178.

24. Heckert, L.L. (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

25. Heckert, L.L. and Griswold, M.D. (2002) "The expression of the FSH receptor in Spermatogenesis" Recent Progress in Hormone Research Vol. 57 in press

26. Lei N and Heckert, L.L. (2002) "Sp1 and Egr1 regulate transcription of the Dmrt1 gene in Sertoli cells" Biology or Reproduction in press