Ed Schmidt, Associate Professor

Veterinary Molecular Biology P.O. Box 173610 Montana State University Bozeman, MT 59717 (406) 994-6375 eschmidt@montana.edu

Research Interests

My primary research interests are to understand the intricate gene regulatory mechanisms that function in development and maintenance of complex organisms, like ourselves.  Much of our work involves analyses of mouse lines we produce that bear targeted mutations (e.g., "knockouts"); however, our approaches to understanding the roles of the mutated genes are broad, including phylogenetics, genetics, biochemistry, molecular biology, histology, biophysics, genomics, proteomics, and other techniques.  The biological processes we are studying include early embryonic patterning and development, placental physiology, germ cell maturation, immune cell functions, the maternal/fetal immune interaction, liver development and regeneration, nucleotide metabolism, imprinting, transcription, and stem cell biology.

Schmidt Laboratory Home Page

Education

• B.S., B.A. University of Montana, Missoula, MT 1981-1985 Biology, Microbiol, Zoology
• Ph.D. Oregon State University, Corvallis, OR 1986-1990 Biochemistry & Biophysics
• Postdoc University of Geneva, Geneva, Switzerland 1991-1995 Molecular Biology
• Postdoc University of Utah, Salt Lake City, UT 1996-1999 Molecular Genetics

Professional Experience

• 1986-1990 Ph.D. Student, Oregon State University, Dept. Biochemistry and Biophysics
• 1991-1995 Postdoctoral Assistant, University of Geneva, Dept. Mol. Biol. (group: Ueli Schibler)
• 1996-1999 Postdoctoral Assistant, University of Utah, Dept. Hu. Genet. (group: Mario Capecchi)
• 1999-2002 Assistant Professor, Montana State University, Dept. Veterinary Molecular Biology
• 2002-Pres. Associate Professor, Montana State University, Dept. Veterinary Molecular Biology

Honors and Awards

• 1984-1985 Watkins Honorary Undergraduate Research Scholarship, University of Montana
• 1985 Graduated with Honors, University of Montana
• 1986-1987 NIH Pre-Doctoral Training Grant, Oregon State University
• 1987-1988 N.L. Tartar Pre-Doctoral Research Fellowship, Oregon State University
• 1991-1993 N.I.H.-Fogarty/Swiss National Science Foundataion Post-Doctoral Fellowship
• 1993-1996 State of Geneva (Switzerland) Post-Doctoral Fellowship, University of Geneva
• 1996 Post-Doctoral Fellow supported by the Mather's Charitable Foundation
• 1997-1999 Howard Hughes Medical Institute Fellow of the Life Sciences Research Foundation
• 2001 Received personal letter of commendation from US Senator Conrad Burns
• 2001-2003 Recipient Basil O'Connor New Investigator of the March of Dimes Foundation
• 2002 Elected member of American Society for Biochemistry and Molecular Biology
• 2005 Recipient, NSF Early Career Award

Extramural Grant Activity

Ongoing Research Support.

• NSF Career Award, MCB-0446536. (P.I., E.E. Schmidt) "Career: Evolution of a vertebrate-specific 'plug-and jack' interaction."  This project investigates the co-evolution of transcription regulatory proteins with the gene expression machinery in vertebrate animals.
• NIH/NIAID R01AI055739 (P.I., E.E. Schmidt), "The maternal-fetal interaction." This project investigates gene regulatory mechanisms involved in maintaining eutherian pregnancy.

Completed Research Support

• NSF, 0090884, 2/01 - 1/05 "Vertebrate specific transcriptional signaling". Role: P.I. This project investigated evolution of the vertebrate-specific TBP N-terminus and takes a whole-genome approach to evaluating signaling through this protein domain in cells and in animals.
• March of Dimes, 6-FY03-61, 6/03 - 5/06, "Regulation of the maternal/fetal immune interaction". Role: P.I. This project used a mouse model system to look at maternal tolerance.

• USDA-NRI, Seed Grant, 12/01 - 11/03, "Parameters affecting the efficiency of targeted mutagenesis in bovine cells. Role: P.I This project investigated the relationship between targeting vector design and targeting efficiency in bovine cells.
• March of Dimes, Basil O'Connor New Investigator Award, 5-FY00-520, "Regulation of midgestation". Role: P.I. This project investigated defects in gene regulation leading to spontaneous miscarriages in a mouse model system that we developed.
• NIH NICHD, R03-HD35824 7/98 - 6/00, "Disruption of spermatid-specific TBP expression in mice". Role: P.I. This project used targeted mutagenesis to create lines of mice bearing specific mutations in the tbp gene.
• NSF, MONTS Award, 1/00 - 12/00, "Identification of the primary defect causing embryonic lethality in a mutant mouse line. Role: P.I. This project identified the reason that the mice which form the basis for the current proposal die of an interaction defect between the mother's immune system and the placenta.
• NIH NICHHD, R03-HD39242 8/00 - 7/02, "Purifying homogeneous spermatid sub-populations". Role: P.I. This project developed transgenic mice with fluorescent markers that are expressed at different stages of spermiogenesis and developed technology for separating sub-populations of these spermatid by FACS.

Selected Publications ted Publications

1. Long, C., E.S. Suvorova, L. Gomez, H. Nguyen, S. Hadding, M.K. Gross, M.R. Capecchi, E.E. Schmidt, and G.F. Merrill (2009).  Liver-specific deletion of the txnrd 1 gene encoding cytosolic thioredoxin reductase induces a subset of oxidative stress response genes.  In preparation.
2. Van der Heide, D., M.F. Rollins, C.M. Weisend, J.A. Kundert, K. Comstock, E.S. Suvorova, G.F. Merrill, M.R. Capecchi, and E.E. Schmidt (2009).  Txnrd1-independent source of electrons supports de novo dNTP synthesis and full replicative potential in mammalian cells.  In preparation.
3. Comstock, K., C.W. Weisend, J.A. Kundert, D. Van der Heide, E.S. Suvorova, and E.E. Schmidt (2009).  Contributions of progenitor/stem cells to liver development and regeneration.  In preparation.
4. Weisend, C.M., J.A. Kundert, E.S. Suvorova, J.R. Prigge, and E.E. Schmidt (2009).  Cre activity in fetal albCre hepatocytes: utility for developmental studies.  Submitted, in review.
5. Liu, M., B. Rakowski, C.M. Weisend, O. Lucas, E.E. Schmidt, and W.P. Halford (2009).  ICP4 and ICP0 function as a repressor and an antirepressor in a bacteriophage λ-like scheme of herpes simplex gene regulation.  Submitted, in review.
6. Suvorova, E.S., O. Lucas, G.F. Merrill, M.R. Capecchi, and E.E. Schmidt (2009) Cytoprotective NRF2 pathway is induced in chronically Txnrd1-deficient hepatocytes.  PLoS ONE, 4(7):e6158.
7. Prigge, J.R., S.V. Iverson, A.M. Siders, and E.E. Schmidt (2009).  Expanded interactome for auxiliary splicing factor U2AF2 Suggests role as information hub.  BBA Gene Reg. Mech.  In press, e-pub 18 June 2009
8. Kundert, J.A., Sealey, A.L., Li, Y., Capecchi, M.R., and Schmidt, E.E. (2008) Syngeneic immune-dependent abortions in mice suggest parternal alloantigen-independent mechanisms.  Am. J. Reprod. Immunol.  60: 290-297.

9. Prigge, J.P., O. Lucas and E.E. Schmidt (2007).  HAP1 can sequester a subset of TBP in cytoplasmic inclusions via specific interaction with the conserved TBPcore.  BMC Mol. Biol.  8: 76-94.

10. Schmidt, E.E. and C.J. Davies (2007).  The origins of polypeptide domains.  BioEssays, 29: 262-270.

11. Sansinena M.J., S.A. Taylor, P.J. Taylor, E.E. Schmidt, R.S. Denniston, and R.A. Godke (2007). In vitro production of llama (Lama glama) embryos by intracytoplasmic sperm injection: effect of chemical activation treatments and culture conditions.  Anim Reprod Sci.. 99: 342-353.

12. Bondareva, A.A., M.R. Capecchi, S.V. Iverson, Y. Li, N.I. Lopez, O. Lucas, G.F. Merrill, J.P. Prigge, A.M. Siders, M. Wakamiya, S.L. Wallin,  and E.E. Schmidt (2007).  Effects of thioredoxin reductase-1 deletion on embryogenesis and transcriptome.  Free. Rad. Biol. Med.  43;911-923.

13. Prigge, J.R. and Schmidt, E.E. (2006). Interaction of protein inhibitor or activated STAT (PIAS) proteins with the TATA-binding protein, TBP.  J. Biol. Chem. 281:12260-12269.

14. Tucker, T.A., Kundert, J.A., Bondareva, A.A. and Schmidt, E.E. (2005) Reproductive and neurological Quaking(viable) phenotypes in a severe combined immune deficient mouse background. Immunogenetics 57, 226-231. [Paper, .pdf]
15. Bondareva, A.A. and Schmidt, E.E. (2003). Early vertebrate evolution of the TATA-binding protein. Mol. Biol. Evol. 20, 1932-1939. [PUBMED-Abstract]
16. Schmidt, E.E., Bondareva, A.A., Radke, J.R., and Capecchi, M.R. (2003) Fundamental cellular processes do not require verterbrate-specific sequences within the TATA-binding protein, TBP. J. Biol. Chem. 278, 6168-6174. [PUBMED-Abstract]
17. Hobbs, N.K., A.A. Bondareva, S. Barnett, M.R. Capecchi, and E.E. Schmidt (2002) Removing the vertebrate-specific TBP N terminus disrupts placental b2m-dependent interactions with the maternal immune system. Cell 110, 43-54. [PUBMED-Abstract]
18. Sealey, A.L., N.K. Hobbs, and E.E. Schmidt (2002) Molecular genotyping of the mouse scid allele. J. Imm. Meth. 260;303-304. [PUBMED-Abstract]
19. Schmidt, E. E., D. S. Taylor, J. R. Prigge, S. Barnett, and M. R. Capecchi (2000) Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids. Proc. Natl. Acad. Sci USA, 97;13702-13707. [PUBMED-Abstract]
20. Schmidt, E. E., E. S. Hanson, and M. R. Capecchi (1999) Sequence-independent assembly of mRNAs into mRNP particles in spermatids. Mol. Cell. Biol. 19;3904-3915. [PUBMED-Abstract]
21. Schmidt, E. E., Ohbayashi, T., Makino, Y., Tamura, T.-a., and U. Schibler (1997) Spermatid-specific overexpression of the TATA-binding protein gene involves recruitment of two potent testis specific promoters. J. Biol. Chem. 272;5326-5334. [PUBMED-Abstract]
22. Schmidt, E. E., and U. Schibler (1997) Developmental testis-specific regulation of mRNA levels and mRNA translational efficiencies for TATA-binding protein mRNA isoforms. Dev. Biol. 184;138-149. [PUBMED-Abstract]
23. Schmidt, E. E. (1996) Transcriptional promiscuity in testis. Curr. Biol. 6;768-769. [no abstract available-first paragraph on BioMednet]
24. Ohbayashi, T., Schmidt, E. E., Makino, Y., Kishimoto, T., Nabeshima, Y.-i., Muramatsu, M., and Tamura, T.-a. (1996) Promoter structure of the mouse TATA-binding protein (TBP) gene. Biochem. Biophys. Res. Comm. 225;275-280. [PUBMED-Abstract]
25. Schmidt, E. E., and U. Schibler (1995) Cell size regulation, a mechanism that controls cellular RNA accumulation: Consequences on regulation of the ubiquitous transcription factors Oct1 and NF-Y, and the liver-enriched transcription factor DBP. J. Cell Biol. 128;467-483. [PUBMED-Abstract]
26. Schmidt, E. E., and U. Schibler (1995) High accumulation of components of the RNA polymerase II machinery in rodent spermatids. Development 121;2373-2383.
27. Schmidt, E.E., and G.F. Merrill (1991).  Changes in dihydrofolate reductase (DHFR) mRNA levels can account fully for changes in DHFR synthesis rates during terminal differentiation in a highly amplified myogenic cell line.  Mol. Cell. Biol. 11;3726-3734.
28. Rawson, C.L., D.T. Loo, J.R. Duimstra, O.R. Hedstrom, E.E. Schmidt, and D.W. Barnes (1991).  Death of serum-free mouse embryo (SFME) cells caused by epidermal growth factor deprivation.  J. Biol. Chem. 113;671-680.
29. Schmidt, E.E., R.A. Owen, and G.F. Merrill (1990).  An Intragenic Region Downstream from the Dihydrofolate Reductase Promoter is Required for Replication-Dependent Expression. J. Biol. Chem. 265;17397-17400.
30. Schmidt, E.E., and G.F. Merrill (1989).  Transcriptional repression of the mouse dihydrofolate reductase gene during muscle cell commitment.  J. Biol. Chem. 264;21247-21256
31. Schmidt, E.E., and G.F. Merrill (1989).  Maintenance of dihydrofolate reductase enzyme after disappearance of DHFR mRNA during muscle cell differentiation.  In Vitro Cell. Dev. Biol. 25;697-704.

Other Publications

1. Lavery, D.J. E.E. Schmidt, and U. Schibler (1996).  "The PAR transcription factor family and circadian gene expression."  In, Vistas on Biorhythmicity: H. Greppin, R. Degli Agosti, and M. Bonzon, eds.  University of Geneva Press.  pp. 135-145.
2. Wuarin, J., E. Falvey, D. Lavery, D. Talbot, E. Schmidt, V. Ossipow, P. Fonjallaz, and U. Schibler (1992).  The role of the transcriptional activator protein DBP in circadian liver gene expression.  J. Cell Sci. supplement 16;123-127.
3. Merrill, G.F., M.K. Gross, E.E. Schmidt, T. Jacobsen, and C.O. Scarlet (1989).  "Identification of a translational mechanism that regulates levels of an enzyme involved in DNA precursor synthesis."  In Molecular Biology of Aging: UCLA Symposia on Molecular and Cellular Biology Vol 123.  Wiley-Liss, New York.  pp.217-230.

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