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Jay Groppe

GroppeAssociate Professor
Department of Biomedical Sciences
Member of the GSBS Faculty

3302 Gaston Ave.
Dallas, Texas 75246
Phone: 214-370-7203
Fax: 214-874-4538
Email: jgroppe@bcd.tamhsc.edu

Education and Post-Graduate Training

Postdoctoral Fellowship, Developmental Biology, Protein Chemistry, University of Basel, Switzerland (1993-1999)

Postdoctoral Fellowship, Bioorganic Chemistry, University of California at Santa Barbara (1992-1993)

Ph.D., Biochemistry - Molecular Biology, University of California at Santa Barbara (1991)

B.A., Biochemistry - Molecular Biology, University of California at Santa Barbara (1980)

Career History

Associate Professor, Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry (2007-present)

Assistant Professor/Research, Department of Biochemistry, University of Texas Health Science Center at San Antonio (2003-2007)

Visiting Scientist, Structural Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA (2000-2003)

Postdoctoral Scientist, Department of Cell Biology, Biozentrum, University of Basel, Switzerland (1993-1999)

Postdoctoral Scientist, Department of Chemistry, University of California at Santa Barbara (1992-1993)

Lecturer, Upper Division General Biochemistry, Department of Biological Sciences, University of California at Santa Barbara (Jan-Apr, 1987)

Teaching Interests

Teaching responsibilities include:

  • Biochemistry, Molecular and Cellular Biology (Dental D1, course 6510)
  • Current Topics in Cell Signaling (BMP Signaling; Medical Sciences graduate course MSCI 612)
  • Cell and Molecular Biology of Oral and Craniofacial Tissues (Membranes, Signal Transduction; Biomedical Sciences graduate course 5V40)

Research Interests

Over the last decade and a half, Dr. Groppe’s (pronounced GRAWP-ee’s) research has focused on the structure and function of Bone Morphogenetic Proteins (BMPs), signal ligands that play fundamental roles throughout embryonic development, including not only formation of bone but also tooth and craniofacial structures.  Initiated as an independent direction in the laboratory of Markus Affolter at the Biozentrum (Basel, Switzerland), this work spawned a collaboration with Senyon Choe, and as a visiting scientist in the Structural Biology Laboratory at the Salk Institute for Biological Studies (La Jolla, California), culminated in determination of crystal structures of BMP-7 trapped by the cystine knot antagonist Noggin 
(middle right) and complexed with type II receptor ECDs (below right).

As a Research Professor in the Department of Biochemistry at the UT Health Science Center at San Antonio, these studies were extended with Andrew Hinck to investigate the mechanism of cooperative assembly of signaling complexes by structurally related yet functionally distinct ligands, Transform
ing Growth Factor-βs (TGF-βs).  That effort led to the determination of the crystal structure of TGF-β3 (an obligate inducer of palatal fusion) in complex with both pairs of its 
receptors (left), revealing quite unexpectedly that the families of structurally related ligands and receptors assemble by strikingly different molecular mechanisms.  

Because of their crucial roles in development and disease, rendering them important targets for therapeutic intervention, Noggin and related cystine knot antagonists such as Gremlin and Cerberus have remained the 
focus of ongoing protein structure-function studies.  A second major front in the study of the inhibition of BMP signaling has emerged through collaboration with Frederick Kaplan and Eileen Shore (University of Pennsylvania School of Medicine) who recently identified a mutant BMP receptor as the source of a severely disabling childhood disorder, Fibrodysplasia Ossificans Progressiva or FOP.  Results of a modeling study (left) based on the crystal structure of the TGF-β receptor kinase have lead to the hypothesis that a common histidine for arginine substitution introduces an aberrant pH-sensitive switch into the regulatory region of the BMP receptor kinase, allowing for ligand-independent activation of the receptor in FOP.  Crystal structures of kinase domains of wild-type and mutant receptors will be determined to identify precisely how this mutation, and others associated with atypical and variant forms of FOP, alter the three-dimensional structure of the protein and to provide models for rational design of ATP analog inhibitors targeted at the dysregulated receptor kinases.

Recent Grants

  • Structural Basis of ACRV1 Dysregulation in Fibrodysplasia Ossificans Progressiva; The Center for Research in Fibrodysplasia Ossificans Progressiva and Related Disorders; University of Pennsylvania School of Medicine; 12/01/06-11/30/13.  (PI)
  • Mechanisms of BMP Receptor Kinase Dysregulation in Skeletal Dysplasias.  NIH/NIAMS R03 (1R03 AR056838-01); 12/15/08-11/30/12. (PI)
  • The Roles of FAM20C (DMP4) in Odontogenesis and Osteogenesis. NIH/NIDCR R01 (1R01 DE022549-01A1); 12/01/12 - 11/30/17. (Co-I)

Selected Publications

1.  Ferguson, J., Groppe, J.C., and Reed, S.I. (1981).  Construction and characterization of three yeast-Escherichia coli shuttle vectors designed for rapid subcloning of yeast genes on small DNA fragments. Gene 16:191-197.   

2.  Reed, S.I., Ferguson, J., and Groppe, J.C.  (1982).  Preliminary characterization of the transcriptional and translational products of the Saccharomyces cerevisiae cell division cycle gene CDC 28. Mol. Cell. Biol. 2:412-425.  

3.  Groppe, J.C. and Morse, D.E. (1993).  Isolation of full-length RNA templates for reverse transcription from tissues rich in RNase and proteoglycans. Anal. Biochem. 210:337-343.   

4.  Groppe, J.C. and Morse, D.E. (1993).  Molluscan chymotrypsin-like protease: Structure, localization and substrate specificity.  Arch. Biochem. Biophys. 305:159-169.   

5.  Hansma, H.G., Sinsheimer, R.L., Groppe, J., Bruice, T.C., Elings, V., Gurley, Gl., Bezanilla, M., Mastrangelo, I.A., Hough, P.V.C. and Hansma, P.K. (1993).  Recent advances in atomic force microscopy of DNA.  Scanning15:296-299.   

6.  He, G.-X., Browne, K.A., Groppe, J.C., Blasko, A., Mei, H-Y., and Bruice, T.C. (1993).  Microgonatropens and their interactions with DNA.  I. Synthesis of the tri-pyrrole peptides dienmicrogonatropen-a,-b,-c and characterization of their interactions with dsDNA.  J. Am. Chem. Soc. 115:7061-7071.

7.  Bregnant, T.M., Groppe, J., and Little, R.D. (1994).  New class of DNA-cleaving agents based on trimethylenemethane.  J. Am. Chem. Soc. 116:3635-3636.   

8.  Affolter, M., Montagne, J., Walldorf, U., Groppe, J., Kloter, U., LaRosa, M. and Gehring, W.J. (1994).  The Drosophila SRF homolog is expressed in a subset of tracheal cells and maps within a genomic region required for tracheal development.  Development 120:743-753.   

9.  Groppe, J.C. and Morse, D.E. (1995).  Sequence-independent detection of gene family homologs: Identification of a transcript encoding a molluscan serine protease homologous to the pancreatic enzymes of vertebrates.  Comp. Biochem. Physiol. 110B:75-82.  

10.  Degnan, B.M., Groppe, J.C., and Morse, D.E. (1995).  Chymotrypsin mRNA expression in digestive gland amoebocytes: Cell specification occurs prior to metamorphosis and gut morphogenesis in the gastropod, Haliotis rufescens.  Roux's Arch. Dev. Biol. 205:97-101.   

11.  Guillemin, K., Groppe, J., Ducker, K., Treisman, R., Hafen, E., Affolter, M. and Krasnow, M.A. (1996).  The pruned gene encodes the Drosophila serum response factor and regulates cytoplasmic outgrowth during terminal branching of the tracheal system. Development 122:1353-1362.   

12.  Montagne, J., Groppe, J., Guillemin, K., Krasnow, M.A., Gehring, W.J. and Affolter., M. (1996). The Drosophila serum response factor gene is required for the formation of intervein tissue of the wing and is allelic to blistered. Development 122:2589-2597.  

13.  Groppe, J., Rumpel, K., Economides, A.N., Stahl, N., Sebald, W. and Affolter, M.  (1998). Biochemical and biophysical characterization of refolded Drosophila DPP, a homolog of bone morphogenetic proteins 2 and 4. J. Biol. Chem. 273:29052-29065.   

14.  Nussbaumer, J., Halder, G., Groppe, J., Affolter, M. and Montagne, J. (2000).  Expression of the blistered/DSRF gene is controlled by different morphogens during Drosophila trachea and wing development. Mech Dev. 96:27-36.   

15.  Perrin, M.H., Fischer, W.H., Kunitake, K.S., Craig, A.G., Koerber, S.C., Cervini, L.A., Rivier, J.E., Groppe, J.C., Greenwald, J., Nielsen, S.M., and Vale, W.W. (2001).  Expression, purification, and characterization of a soluble form of the first extracellular domain of the human type 1 corticotropin releasing factor receptor.  J. Biol. Chem.276:31528-31534.   

16.  Groppe, J., Greenwald., J., Wiater, E., Rodriguez-Leon, J., Economides, A., Kwiatkowski, W., Affolter, M., Vale, W.W., Izpisua-Belmont, J.C. and Choe, S. (2002).  Structural basis of BMP signalling inhibition by the cystine knot protein Noggin.  Nature 420:636-642.  

[Commented on by Wrana, J. (2002). Structural biology: On the wings of inhibition.  Nature 420:613-614; also highlighted by UCSD/Nature Signaling Gateway (Dec 2002).  BMP signal inhibition by Noggin: The shape of things to come, online].

17.  Greenwald, J., Groppe, J., Gray, P., Wiater, E., Kwiatkowski, W., Vale, W.W., and Choe, S. (2003).  The BMP7/ActRII extracullular domain complex provides new insights into the cooperative nature of receptor assembly. Mol. Cell. 11:605-617.

[Commented on by Sebald, W. and Mueller, T.D. (2002). The interaction of BMP-7 and ActRll implicates a new mode of receptor assembly.  Trends Biochem Sci 28:518-521 and Sun, P.D. (2003).  Conserved in structure but diverse in recognition.  Structure 11:362-363.]

18.  Groppe, J., Greenwald, J. Wiater, E., Rodriguez-Leon, J., Economides, A., Kwiatkowski., W. Baban, K., Affolter, M., Vale, W.W., Izpisúa-Belmonte, J.C. and Choe, S. (2003).  Structural basis of BMP signaling inhibition by Noggin, a novel twelve-membered cystine knot protein.  J. Bone Joint Surg. Am 85-A, Supplement 3: 52-58.

19.  Ilangovan, J., Ding, W., Zhong, Y., Wilson, C.L., Groppe, J.C., Trbovich, J.T., Zúñiga, J., Demeler, B., Tang, Q., Gao, L., Mulder, K.M. and Hinck, A.P. (2005).  Structure and dynamics of the homodimeric dynein light chain km23. J. Mol. Biol. 352:338-354.   

20.  Zúñiga, J.E., *Groppe, J.C., Cui, Y., Hinck, C.S., Contreras-Shannon, V., Pakhomova, O.N., Yang, J., Tang, Y., Mendoza, V., López-Casillas, F., Sun, L.-Z., and Hinck, A.P. (2005).  Assembly of TβRI:TβRII:TGFβ ternary complex in vitro with receptor extracellular domains is cooperative and isoform-dependent.  J. Mol. Bio.  354:1052-1068  (*equal first author, wrote paper).   

21.  Groppe, J.C., Shore, E.M. and Kaplan, F.S. (2007).  Functional modeling of the ACVR1 (R206H) mutation in FOP.  Clin. Orthop. Relat. Res. 462:87-92.   

22.  Kaplan, F.S., Groppe, J., Pignolo, R.J., and Shore, E.M. (2007).  Morphogen receptor genes and metamorphogenes: Skeleton keys to metamorphosis.  Ann. NY Acad. Sci. 1116:113-133.

23.  Groppe, J., Hinck, C.S., Samavarchi-Tehrani, P., Zubieta, C., Schuermann, J.P., Taylor, A.B., Schwarz, P.M., Wrana, J.L. and Hinck, A.P. (2008). Cooperative assembly of TGF-β superfamily signaling complexes is mediated by two disparate mechanisms and distinct modes of receptor binding.  Mol. Cell 29:157-168.

[Commented on by Massagué, J. (2008). A very private TGF-β receptor embrace. Mol. Cell 29:149-150;  Gough, N.R. (2008).  Monogamy in the TGF-β receptor relationship.  Science Signaling Vol 1 (5):46; and Montoya, M. (2008).  Signaling distinctions.  Nat. Struct. Mol. Biol. 15:227.]

24.  Kaplan, F.S., Le Merrer, M., Glaser, D.L., Pignolo, R.J., Goldsby, R.E., Kitterman, J.A., Groppe, J., Shore, E.M. (2008).  Fibrodysplasia ossificans progressiva.  Best Pract. Res. Clin. Rheumatol. 22:191-205.

25.  Kaplan, F.S., Shen, Q., Lounev, V., Seeman, P., Groppe J., Katagiri T., Pignolo, R.J., Shore, E.M. (2008). Skeletal metamorphosis in Fibrodysplasia Ossificans Progressiva (FOP).  J. Bone Miner. Res. 26:521-530.

26. Kaplan, F.S., Groppe, J., and Shore, E.M. (2008).  When one skeleton is enough: Approaches and strategies for the treatment of fibrodysplasia ossificans progressiva (FOP). Drug Discov. Today Ther. Strateg. 5:255-262.

27.  Kaplan, F.S., Xu, M., Seemann, P., Connor, M., Glaser, D.L., Carroll, L., Delai, P., Fastnacht-Urban, E., Forman, S.J., Gillessen-Kaesbach, G., Hoover-Fong, J., Köster, B., Pauli, R.M., Reardon, W., Zaidi, S.-A., Zasloff, M., Morhart, R., Mundlos, S., Groppe, J., and Shore, E.M. (2009).  Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1.  Hum. Mutat. 30:379-90.

28.  Wang, Y., Groppe, J.C., Wu, J., Ogawa ,T., Mues, G., D'Souza, R.N., Kapadia, H. (2009).  Pathogenic mechanisms of tooth agenesis linked to paired domain mutations in human PAX9.  Hum. Mol. Genet. 18:2863-2874.

29.  Nickel, J., Sebald, W., Groppe, J.C., Mueller, T.D. (2009). Intricacies of BMP receptor assembly. Cytokine Growth Factor Rev. 20:367-77.

30.  Seemann, P., Brehm, A., König, J., Reissner, C., Stricker, S., Kuss, P., Haupt ,J., Renninger, S., Nickel, J., Sebald, W., Groppe, J.C., Plöger, F., Pohl, J., Schmidt-von Kegler, M., Walther, M., Gassner, I., Rusu, C., Janecke, A.R., Dathe, K., Mundlos, S. (2009). Mutations in GDF5 reveal a key residue mediating BMP inhibition by NOGGIN. PloS Genet. 5:e1000747. 

31. Kaplan, F.S., Groppe, J., Seeman, P., Pignolo, R.J. and Shore, E.M. (2010).  Fibrodysplasia ossificans progressiva: Developmental implications of a novel metamorphogene.  Bone and Development (Vol. 6). Topics in Bone Biology, Chapter 14.  Bronner, Farach-Carson and Roach, editors.

32.  Kuhfahl, S., Hauburger, A., Thieme, T., Groppe, J., Ihling, C., Tomic, S., Schutkowski, M., Sinz, A., Schwarz, E. (2011).  Identification of a core domain within the proregion of bone morphogenetic proteins that interacts with the mature, dimeric domain.  Biochem. Biophys. Res. Commun. 408:300-305.

33. Groppe, J., Wu, J., Shore, E.M., Kaplan, F.S. (2011). In vitro analysis of the dysregulated R206H ALK2 Kinase-FKBP12 interaction associated with heteroscopic ossification in FOP.  Cells Tissues Organs 194:291-295.

34. Ishii, Y., Takizawa, T., Iwasaki, H., Fujita, Y., Murakami, M., Groppe, J.C., Tanaka, K. (2012).  Nucleotide polymorphisms in the canine Noggin (NOG) gene and their distribution among dog (Canis lupus familiaris) breeds. Biochemical Genetics 50: 12-18.

35. Zimmer, J., Doelken, S., Horn, D., Groppe, J., Shore, E., Kaplan, F., Seemann P. (2012).  Functional analysis of alleged NOGGIN mutation G92E disproves its pathogenic relevance.  PLoS ONE 7(4): e35062.

36. Wang, X., Wang, S., Li, C., Gao, T., Liu,Y., Rangiani, A., Sun, Y., Hao, J., George, A., Lu, Y., Groppe, J., Yuan, B., Feng, J., Qin C. (2012).  Inactivation of a novel FGF23 regulator, FAM20C, leads to hypophosphatemic rickets in mice.  PLoS Genetics 8(5): e1002708.

37. Whitman, M., Rosen, V., Brivanlou, A.H., Groppe, J.C., Sebald, W., Mueller, T. (2013).  Regarding the mechanism of action of a proposed peptide agonist of the bone morphogenetic protein receptor activan-like kinase 3.  Nat Med 19:809-810.

Last edited by: aupton 07/24/2014

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