Michael D. Sheets

Associate Professor

683 Medical Sciences Center
1300 University Avenue
Madison WI 53706-1532

Office: (608) 262-9452

Fax: (608) 262-5253

mdsheets@wisc.edu

Education

B.S. 1982, Purdue University;
Ph.D. 1989, University of Wisconsin;
Postdoctoral 1990-1992, University of Wisconsin (M. Wickens); Postdoctoral 1992-1996, University of California, Berkeley (J. Gerhart).

Honors & Awards

American Cancer Society Fellow, 1995;
March of Dimes Basil O'Connor Scholar, 1997;
Pew Scholar, 1998; Beckman Young Investigator Award, 1998.

Research Interests

The goal of our research is to understand how signaling pathways and gene expression collaborate to control the earliest cell differentiation events in vertebrate embryos. To pursue this goal we are elucidating the mechanisms that regulate the extracellular signals produced by the organizer, a localized group of cells in embryos of the frog, Xenopus laevis. The organizer cells secrete specific signaling proteins, such as chordin, that direct adjacent mesodermal cells to form tissues such as muscle and kidney. Non-organizer cells produce signals such as the secreted BMPs (bone morphogenetic proteins) that counteract the secreted organizer proteins. The balance between organizer-specific signals (i.e. chordin) and non-organizer signals (i.e. BMPs) determines when and where specific tissues form in the embryo.

To understand how this critical balance is achieved, we have focussed on the mechanisms that regulate chordin expression by the organizer cells and the mechanisms that regulate BMP expression by non-organizer cells. Our results demonstrate that organizer-specific transcriptional processes regulate chordin expression. Currently, we are using bioinformatics to define regulatory sites in the chordin promoter and biochemical approaches to define the corresponding transcription factors that limit its expression to the organizer cells. In contrast, the expression of BMP proteins in the early embryo is regulated by mechanisms that govern mRNA translation. In the case of BMP 7 this regulation is conferred by novel sequence elements present in the 3’ untranslated region of the BMP 7 mRNA. We are using an in vitro processing system derived from embryos and RNA-affinity chromatography to identify the proteins that bind these elements and biochemical studies to define how they affect translation. These recent findings provide new insights into the fundamental events of vertebrate development and lead to many new and exciting research opportunities in the laboratory.

Publications of Note

Sheets, M.D. (1998) Turning the frog into a princely model. Nature
Biotechnology 16: 233-234.

Sheets, M.D., Amersdorfer, P., Finnern, R., Sargent, P., Schier, R.,
Wong, C., Gerhart, J., and J. Marks. (1998) Efficient construction of a
large non-immune phage antibody library: the production of panels of
high affinity human single chain antibodies to protein antigens. PNAS
95(11):6157-62.

Lane, M. C. and M.D Sheets. (2000). Designation of the anterior/
posterior axis in pre-gastrula Xenopus embryos. Developmental Biology
220(1): 37-58.

Fritz, B.R, and M.D. Sheets. (2001) Regulation of the mRNAs encoding
proteins of the BMP signaling pathway during the maternal stages of
Xenopus development. Developmental Biology 236(1): 230-243.

Wong C. Waibel R. Sheets M.D. Mach JP. Finnern R. (2001) Human scFv
antibody fragments specific for the epithelial tumour marker MUC-
1,selected by phage display. Cancer Immunotherapy. 50(2): 93-101.

Mitchell T.M., and M.D. Sheets. (2001) The FGFR pathway is required for
the trunk-inducing functions of Spemann’s organizer. Developmental
Biology. 237(2): 295-305.

Lane, M. C. and M.D Sheets. (2002). Primative and definitive blood
share a common origin in Xenopus embryos. Developmental Biology (248)
52-67.

Audic, Y. Fritz, B. Garbrecht, M. Sheets, M.D. and R. S. Hartley
(2002). Zygotic control of maternal cyclin A1 translation.
Developmental Dynamics 225 (4) 511-521.

Lane, M. C. and M.D Sheets. (2002). Rethinking axial patterning in
Xenopus embryos (Review). Developmental Dynamics 225 (4) 434-447.

Abler L.L., and M.D. Sheets (2003) Expression of scFv antibodies in
Xenopus embryos to disrupt protein function: implications for large-
scale evaluation of the embryonic proteome. Genesis 35(2) 107-113.

Lane, M. C. and M.D. Sheets (2004) Fate Mapping Hematopoietic Lineages
in the Xenopus Embryo. Methods in Molecular Medicine. 105:137-48, 2004.
Good PJ. Abler L. Herring D. Sheets MD. (2004) Xenopus embryonicpoly(A)
binding protein 2 (ePABP2) defines a new family of cytoplasmic Poly(A)
binding proteins expressed during the early stages of vertebrate
development. Genesis. 38(4):166-175.

Lane, M. C. Davidson, L., and M.D. Sheets (2004) BMP antagonism by
Spemann's organizer regulates rostral/caudal fate of mesoderm.
Developmental Biology. 275(2):356-74, 2004.