Doctoral Students
Emily Kappes: 2018-2023
Scientist - Meridian Bioscience
Molecular Characterization of the Inhibin A Heterodimer and its Function as an Activin Antagonist
Kappes, E. C., Kattamuri, C., Czepnik, M., Yarawsky, A. E., Brûlé, E., Wang, Y., Ongaro, L., Herr, A. B., Walton, K. L., Bernard, D. J. & Thompson, T. B. Follistatin Forms a Stable Complex With Inhibin A That Does Not Interfere With Activin A Antagonism. Endocrinology 164, bqad017 (2023).
Goebel, E. J., Ongaro, L., Kappes, E. C., Vestal, K., Belcheva, E., Castonguay, R., Kumar, R., Bernard, D. J. & Thompson, T. B. The orphan ligand, activin C, signals through activin receptor-like kinase 7. eLife 11, e78197 (2022).
Gipson, G. R., Goebel, E. J., Hart, K. N., Kappes, E. C., Kattamuri, C., McCoy, J. C. & Thompson, T. B. Structural perspective of BMP ligands and signaling. Bone 140, 115549 (2020).
Gregory Gipson: 2017-2022
Postdoctoral Fellow - Harvard
Mechanistic Insights into Understudied Components of the Extracellular Modulation of BMP Signaling
Ramachandran, D., Kotikalapudi, N., Gipson, G. R., Troncone, L., Vestal, K., Maridas, D. E., Gulko, A., Tsai, L. T., Rosen, V., Yu, P., Thompson, T. B. & Banks, A. S. GDF3 is an obesity-induced regulator of TGFβ superfamily signaling. 2022.11.07.515236 Preprint at https://doi.org/10.1101/2022.11.07.515236 (2023)
Gipson, G. R., Nolan, K., Kattamuri, C., Kenny, A. P., Agricola, Z., Edwards, N. A., Zinski, J., Czepnik, M., Mullins, M. C., Zorn, A. M. & Thompson, T. B. Formation and characterization of BMP2/GDF5 and BMP4/GDF5 heterodimers. BMC Biol 21, 16 (2023). PDB: 8E3G
Goebel, E. J., Kattamuri, C., Gipson, G. R., Krishnan, L., Chavez, M., Czepnik, M., Maguire, M. C., Grenha, R., Håkansson, M., Logan, D. T., Grinberg, A. V., Sako, D., Castonguay, R., Kumar, R. & Thompson, T. B. Structures of activin ligand traps using natural sets of type I and type II TGFβ receptors. iScience 25, 103590 (2022). PDB: 7MRZ
Rydze, R. T., Patton, B. K., Briley, S. M., Salazar Torralba, H., Gipson, G., James, R., Rajkovic, A., Thompson, T. & Pangas, S. A. Deletion of Gremlin-2 alters estrous cyclicity and disrupts female fertility in mice†. Biol Reprod 105, 1205–1220 (2021).
Gipson, G. R., Goebel, E. J., Hart, K. N., Kappes, E. C., Kattamuri, C., McCoy, J. C. & Thompson, T. B. Structural perspective of BMP ligands and signaling. Bone 140, 115549 (2020).
Gipson, G. R., Kattamuri, C., Czepnik, M. & Thompson, T. B. Characterization of the different oligomeric states of the DAN family antagonists SOSTDC1 and SOST. Biochem J 477, 3167–3182 (2020).
Kaitlin Hart: 2016-2021
Associate Scientist - Regeneron
Structural and Functional Studies of Anti-Müllerian Hormone (AMH) and its Receptor
Howard, J. A., Hart, K. N. & Thompson, T. B. Molecular Mechanisms of AMH Signaling. Front Endocrinol (Lausanne) 13, 927824 (2022).
Hart, K. N., Stocker, W. A., Nagykery, N. G., Walton, K. L., Harrison, C. A., Donahoe, P. K., Pépin, D. & Thompson, T. B. Structure of AMH bound to AMHR2 provides insight into a unique signaling pair in the TGF-β family. PNAS 118, (2021). PDB: 7L0J
Gipson, G. R., Goebel, E. J., Hart, K. N., Kappes, E. C., Kattamuri, C., McCoy, J. C. & Thompson, T. B. Structural perspective of BMP ligands and signaling. Bone 140, 115549 (2020).
Hart, K. N., Pépin, D., Czepnik, M., Donahoe, P. K. & Thompson, T. B. Mutational Analysis of the Putative Anti-Müllerian Hormone (AMH) Binding Interface on its Type II Receptor, AMHR2. Endocrinology 161, (2020).
Goebel, E. J., Hart, K. N., McCoy, J. C. & Thompson, T. B. Structural biology of the TGFβ family. Exp. Biol. Med. (Maywood) 244, 1530–1546 (2019).
Erich Goebel: 2015-2021
Postdoctoral Fellow - Regeneron
Insights into the Activin Class: Mechanisms of Receptor Assembly and Specificity
Goebel, E. J., Ongaro, L., Kappes, E. C., Vestal, K., Belcheva, E., Castonguay, R., Kumar, R., Bernard, D. J. & Thompson, T. B. The orphan ligand, activin C, signals through activin receptor-like kinase 7. eLife 11, e78197 (2022).
Goebel, E. J., Kattamuri, C., Gipson, G. R., Krishnan, L., Chavez, M., Czepnik, M., Maguire, M. C., Grenha, R., Håkansson, M., Logan, D. T., Grinberg, A. V., Sako, D., Castonguay, R., Kumar, R. & Thompson, T. B. Structures of activin ligand traps using natural sets of type I and type II TGFβ receptors. iScience 25, 103590 (2022). PDB: 7MRZ
McCoy, J. C., Goebel, E. J. & Thompson, T. B. Characterization of tolloid-mediated cleavage of the GDF8 procomplex. Biochem J (2021).
Walker, R. G., Kattamuri, C., Goebel, E. J., Zhang, F., Hammel, M., Tainer, J. A., Linhardt, R. J. & Thompson, T. B. Heparin-mediated dimerization of follistatin. Exp Biol Med (Maywood) 246, 467–482 (2021).
Gipson, G. R., Goebel, E. J., Hart, K. N., Kappes, E. C., Kattamuri, C., McCoy, J. C. & Thompson, T. B. Structural perspective of BMP ligands and signaling. Bone 140, 115549 (2020).
Aykul, S., Corpina, R. A., Goebel, E. J., Cunanan, C. J., Dimitriou, A., Kim, H. J., Zhang, Q., Rafique, A., Leidich, R., Wang, X., McClain, J., Jimenez, J., Nannuru, K. C., Rothman, N. J., Lees-Shepard, J. B., Martinez-Hackert, E., Murphy, A. J., Thompson, T. B., Economides, A. N. & Idone, V. Activin A forms a non-signaling complex with ACVR1 and type II Activin/BMP receptors via its finger 2 tip loop. Elife 9, (2020).
Goebel, E. J., Hart, K. N., McCoy, J. C. & Thompson, T. B. Structural biology of the TGFβ family. Exp. Biol. Med. (Maywood) 244, 1530–1546 (2019).
Goebel, E. J., Corpina, R. A., Hinck, C. S., Czepnik, M., Castonguay, R., Grenha, R., Boisvert, A., Miklossy, G., Fullerton, P. T., Matzuk, M. M., Idone, V. J., Economides, A. N., Kumar, R., Hinck, A. P. & Thompson, T. B. Structural characterization of an activin class ternary receptor complex reveals a third paradigm for receptor specificity. Proc. Natl. Acad. Sci. U.S.A. 116, 15505–15513 (2019). PDB: 6MAC
Walker, R. G., Czepnik, M., Goebel, E. J., McCoy, J. C., Vujic, A., Cho, M., Oh, J., Aykul, S., Walton, K. L., Schang, G., Bernard, D. J., Hinck, A. P., Harrison, C. A., Martinez-Hackert, E., Wagers, A. J., Lee, R. T. & Thompson, T. B. Structural basis for potency differences between GDF8 and GDF11. BMC Biol. 15, 19 (2017). PDBs: 5JI1 5JHW 5UHM
Jason McCoy: 2015-2020
Senior Scientist - Lacerta Therapeutics
Molecular mechanisms of growth differentiation factor 8 (GDF8) latency, activation, and antagonism
McCoy, J. C., Goebel, E. J. & Thompson, T. B. Characterization of tolloid-mediated cleavage of the GDF8 procomplex. Biochem J (2021).
Gipson, G. R., Goebel, E. J., Hart, K. N., Kappes, E. C., Kattamuri, C., McCoy, J. C. & Thompson, T. B. Structural perspective of BMP ligands and signaling. Bone 140, 115549 (2020).
Goebel, E. J., Hart, K. N., McCoy, J. C. & Thompson, T. B. Structural biology of the TGFβ family. Exp. Biol. Med. (Maywood) 244, 1530–1546 (2019).
Cox, T. C., Lidral, A. C., McCoy, J. C., Liu, H., Cox, L. L., Zhu, Y., Anderson, R. D., Moreno Uribe, L. M., Anand, D., Deng, M., Richter, C. T., Nidey, N. L., Standley, J. M., Blue, E. E., Chong, J. X., Smith, J. D., Kirk, E. P., Venselaar, H., Krahn, K. N., van Bokhoven, H., Zhou, H., Cornell, R. A., Glass, I. A., Bamshad, M. J., Nickerson, D. A., Murray, J. C., Lachke, S. A., Thompson, T. B., Buckley, M. F. & Roscioli, T. Mutations in GDF11 and the extracellular antagonist, Follistatin, as a likely cause of Mendelian forms of orofacial clefting in humans. Hum Mutat 40, 1813–1825 (2019).
McCoy, J. C., Walker, R. G., Murray, N. H. & Thompson, T. B. Crystal structure of the WFIKKN2 follistatin domain reveals insight into how it inhibits growth differentiation factor 8 (GDF8) and GDF11. J. Biol. Chem. 294, 6333–6343 (2019). PDB: 6MAA
Cotton, T. R., Fischer, G., Wang, X., McCoy, J. C., Czepnik, M., Thompson, T. B. & Hyvönen, M. Structure of the human myostatin precursor and determinants of growth factor latency. EMBO J. 37, 367–383 (2018).
Walker, R. G., McCoy, J. C., Czepnik, M., Mills, M. J., Hagg, A., Walton, K. L., Cotton, T. R., Hyvönen, M., Lee, R. T., Gregorevic, P., Harrison, C. A. & Thompson, T. B. Molecular characterization of latent GDF8 reveals mechanisms of activation. Proc. Natl. Acad. Sci. U.S.A. 115, E866–E875 (2018).
Walker, R. G., Czepnik, M., Goebel, E. J., McCoy, J. C., Vujic, A., Cho, M., Oh, J., Aykul, S., Walton, K. L., Schang, G., Bernard, D. J., Hinck, A. P., Harrison, C. A., Martinez-Hackert, E., Wagers, A. J., Lee, R. T. & Thompson, T. B. Structural basis for potency differences between GDF8 and GDF11. BMC Biol. 15, 19 (2017). PDBs: 5JI1 5JHW 5UHM
Kristof Nolan: 2011-2016
Senior Scientist - AstraZeneca
Gipson, G. R., Nolan, K., Kattamuri, C., Kenny, A. P., Agricola, Z., Edwards, N. A., Zinski, J., Czepnik, M., Mullins, M. C., Zorn, A. M. & Thompson, T. B. Formation and characterization of BMP2/GDF5 and BMP4/GDF5 heterodimers. BMC Biol 21, 16 (2023). PDB: 8E3G
Bylund, J. B., Trinh, L. T., Awgulewitsch, C. P., Paik, D. T., Jetter, C., Jha, R., Zhang, J., Nolan, K., Xu, C., Thompson, T. B., Kamp, T. J. & Hatzopoulos, A. K. Coordinated Proliferation and Differentiation of Human-Induced Pluripotent Stem Cell-Derived Cardiac Progenitor Cells Depend on Bone Morphogenetic Protein Signaling Regulation by GREMLIN 2. Stem Cells Dev. 26, 678–693 (2017).
Kattamuri, C., Nolan, K. & Thompson, T. B. Analysis and identification of the Grem2 heparin/heparan sulfate-binding motif. Biochem. J. 474, 1093–1107 (2017).
Nolan, K., Kattamuri, C., Rankin, S. A., Read, R. J., Zorn, A. M. & Thompson, T. B. Structure of Gremlin-2 in Complex with GDF5 Gives Insight into DAN-Family-Mediated BMP Antagonism. Cell Rep 16, 2077–2086 (2016). PDB: 5HK5
Sanders, L. N., Schoenhard, J. A., Saleh, M. A., Mukherjee, A., Ryzhov, S., McMaster, W. G., Nolan, K., Gumina, R. J., Thompson, T. B., Magnuson, M. A., Harrison, D. G. & Hatzopoulos, A. K. BMP Antagonist Gremlin 2 Limits Inflammation After Myocardial Infarction. Circ. Res. 119, 434–449 (2016).
Nolan, K., Kattamuri, C., Luedeke, D. M., Angerman, E. B., Rankin, S. A., Stevens, M. L., Zorn, A. M. & Thompson, T. B. Structure of neuroblastoma suppressor of tumorigenicity 1 (NBL1): insights for the functional variability across bone morphogenetic protein (BMP) antagonists. J. Biol. Chem. 290, 4759–4771 (2015). PDB: 4X1J
Nolan, K. & Thompson, T. B. The DAN family: modulators of TGF-β signaling and beyond. Protein Sci. 23, 999–1012 (2014).
Nolan, K., Kattamuri, C., Luedeke, D. M., Deng, X., Jagpal, A., Zhang, F., Linhardt, R. J., Kenny, A. P., Zorn, A. M. & Thompson, T. B. Structure of protein related to Dan and Cerberus: insights into the mechanism of bone morphogenetic protein antagonism. Structure 21, 1417–1429 (2013). PDB: 4JPH
Kattamuri, C., Luedeke, D. M., Nolan, K., Rankin, S. A., Greis, K. D., Zorn, A. M. & Thompson, T. B. Members of the DAN family are BMP antagonists that form highly stable noncovalent dimers. J. Mol. Biol. 424, 313–327 (2012).
Cash, J. N., Angerman, E. B., Kattamuri, C., Nolan, K., Zhao, H., Sidis, Y., Keutmann, H. T. & Thompson, T. B. Structure of myostatin·follistatin-like 3: N-terminal domains of follistatin-type molecules exhibit alternate modes of binding. J. Biol. Chem. 287, 1043–1053 (2012). PDB: 3SEK
Ryan Walker: 2011-2016
Postdoctoral Scholar - Dr. Tom Thompson - University of Cincinnati
Walker, R. G., Kattamuri, C., Goebel, E. J., Zhang, F., Hammel, M., Tainer, J. A., Linhardt, R. J. & Thompson, T. B. Heparin-mediated dimerization of follistatin. Exp Biol Med (Maywood) 246, 467–482 (2021).
McCoy, J. C., Walker, R. G., Murray, N. H. & Thompson, T. B. Crystal structure of the WFIKKN2 follistatin domain reveals insight into how it inhibits growth differentiation factor 8 (GDF8) and GDF11. J. Biol. Chem. 294, 6333–6343 (2019). PDB: 6MAA
Walker, R. G. & Thompson, T. B. New Insight Into Hyperemesis Gravidarum and a Potential Role for GDF15. Endocrinology 159, 2698–2700 (2018).
Walker, R. G., McCoy, J. C., Czepnik, M., Mills, M. J., Hagg, A., Walton, K. L., Cotton, T. R., Hyvönen, M., Lee, R. T., Gregorevic, P., Harrison, C. A. & Thompson, T. B. Molecular characterization of latent GDF8 reveals mechanisms of activation. Proc. Natl. Acad. Sci. U.S.A. 115, E866–E875 (2018).
Melchior, J. T., Walker, R. G., Cooke, A. L., Morris, J., Castleberry, M., Thompson, T. B., Jones, M. K., Song, H. D., Rye, K.-A., Oda, M. N., Sorci-Thomas, M. G., Thomas, M. J., Heinecke, J. W., Mei, X., Atkinson, D., Segrest, J. P., Lund-Katz, S., Phillips, M. C. & Davidson, W. S. A consensus model of human apolipoprotein A-I in its monomeric and lipid-free state. Nat. Struct. Mol. Biol. 24, 1093–1099 (2017).
Walker, R. G., Czepnik, M., Goebel, E. J., McCoy, J. C., Vujic, A., Cho, M., Oh, J., Aykul, S., Walton, K. L., Schang, G., Bernard, D. J., Hinck, A. P., Harrison, C. A., Martinez-Hackert, E., Wagers, A. J., Lee, R. T. & Thompson, T. B. Structural basis for potency differences between GDF8 and GDF11. BMC Biol. 15, 19 (2017). PDBs: 5JI1 5JHW 5UHM
Walker, R. G., Poggioli, T., Katsimpardi, L., Buchanan, S. M., Oh, J., Wattrus, S., Heidecker, B., Fong, Y. W., Rubin, L. L., Ganz, P., Thompson, T. B., Wagers, A. J. & Lee, R. T. Biochemistry and Biology of GDF11 and Myostatin: Similarities, Differences, and Questions for Future Investigation. Circ. Res. 118, 1125–1141; discussion 1142 (2016).
Melchior, J. T., Walker, R. G., Morris, J., Jones, M. K., Segrest, J. P., Lima, D. B., Carvalho, P. C., Gozzo, F. C., Castleberry, M., Thompson, T. B. & Davidson, W. S. An Evaluation of the Crystal Structure of C-terminal Truncated Apolipoprotein A-I in Solution Reveals Structural Dynamics Related to Lipid Binding. J. Biol. Chem. 291, 5439–5451 (2016).
Poggioli, T., Vujic, A., Yang, P., Macias-Trevino, C., Uygur, A., Loffredo, F. S., Pancoast, J. R., Cho, M., Goldstein, J., Tandias, R. M., Gonzalez, E., Walker, R. G., Thompson, T. B., Wagers, A. J., Fong, Y. W. & Lee, R. T. Circulating Growth Differentiation Factor 11/8 Levels Decline With Age. Circ. Res. 118, 29–37 (2016).
Li, N., Yang, Q., Walker, R. G., Thompson, T. B., Du, M. & Rodgers, B. D. Myostatin Attenuation In Vivo Reduces Adiposity, but Activates Adipogenesis. Endocrinology 157, 282–291 (2016).
Walker, R. G. & Thompson, T. B. Fibronectin-based scaffold domain proteins that bind myostatin: a patent evaluation of WO2014043344. Expert Opin Ther Pat 25, 619–624 (2015).
Deng, X., Walker, R. G., Morris, J., Davidson, W. S. & Thompson, T. B. Role of Conserved Proline Residues in Human Apolipoprotein A-IV Structure and Function. J. Biol. Chem. 290, 10689–10702 (2015).
Walker, R. G., Angerman, E. B., Kattamuri, C., Lee, Y.-S., Lee, S.-J. & Thompson, T. B. Alternative binding modes identified for growth and differentiation factor-associated serum protein (GASP) family antagonism of myostatin. J. Biol. Chem. 290, 7506–7516 (2015).
Rodgers, B. D., Wiedeback, B. D., Hoversten, K. E., Jackson, M. F., Walker, R. G. & Thompson, T. B. Myostatin stimulates, not inihibits, C2C12 myoblast proliferation. Endocrinology 155, 670–675 (2014).
Walker, R. G., Deng, X., Melchior, J. T., Morris, J., Tso, P., Jones, M. K., Segrest, J. P., Thompson, T. B. & Davidson, W. S. The structure of human apolipoprotein A-IV as revealed by stable isotope-assisted cross-linking, molecular dynamics, and small angle x-ray scattering. J. Biol. Chem. 289, 5596–5608 (2014).
Zhang, F., Beaudet, J. M., Luedeke, D. M., Walker, R. G., Thompson, T. B. & Linhardt, R. J. Analysis of the interaction between heparin and follistatin and heparin and follistatin-ligand complexes using surface plasmon resonance. Biochemistry 51, 6797–6803 (2012).
Xiaodi 'Andy' Deng: 2007-2013
Senior Research Associate - Stealth Biotech
Apolipoprotein A-IV Structural Determination and Biophysical Characterization
Deng, X., Walker, R. G., Morris, J., Davidson, W. S. & Thompson, T. B. Role of Conserved Proline Residues in Human Apolipoprotein A-IV Structure and Function. J. Biol. Chem. 290, 10689–10702 (2015).
Walker, R. G., Deng, X., Melchior, J. T., Morris, J., Tso, P., Jones, M. K., Segrest, J. P., Thompson, T. B. & Davidson, W. S. The structure of human apolipoprotein A-IV as revealed by stable isotope-assisted cross-linking, molecular dynamics, and small angle x-ray scattering. J. Biol. Chem. 289, 5596–5608 (2014).
Nolan, K., Kattamuri, C., Luedeke, D. M., Deng, X., Jagpal, A., Zhang, F., Linhardt, R. J., Kenny, A. P., Zorn, A. M. & Thompson, T. B. Structure of protein related to Dan and Cerberus: insights into the mechanism of bone morphogenetic protein antagonism. Structure 21, 1417–1429 (2013). PDB: 4JPH
Deng, X., Morris, J., Chaton, C., Schröder, G. F., Davidson, W. S. & Thompson, T. B. Small-angle X-ray scattering of apolipoprotein A-IV reveals the importance of its termini for structural stability. J. Biol. Chem. 288, 4854–4866 (2013).
Deng, X., Morris, J., Dressmen, J., Tubb, M. R., Tso, P., Jerome, W. G., Davidson, W. S. & Thompson, T. B. The structure of dimeric apolipoprotein A-IV and its mechanism of self-association. Structure 20, 767–779 (2012). PDB: 3S84
Deng, X., Davidson, W. S. & Thompson, T. B. Improving the diffraction of apoA-IV crystals through extreme dehydration. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 68, 105–110 (2012).
Jennifer Cash: 2005-2011
Assistant Professor - University of California, Davis
Structural and Biochemical Insights into Myostatin Regulation
Cash, J. N., Angerman, E. B., Kirby, R. J., Merck, L., Seibel, W. L., Wortman, M. D., Papoian, R., Nelson, S. & Thompson, T. B. Development of a small-molecule screening method for inhibitors of cellular response to myostatin and activin A. J Biomol Screen 18, 837–844 (2013).
Cash, J. N., Angerman, E. B., Keutmann, H. T. & Thompson, T. B. Characterization of follistatin-type domains and their contribution to myostatin and activin A antagonism. Mol. Endocrinol. 26, 1167–1178 (2012).
Cash, J. N., Angerman, E. B., Kattamuri, C., Nolan, K., Zhao, H., Sidis, Y., Keutmann, H. T. & Thompson, T. B. Structure of myostatin·follistatin-like 3: N-terminal domains of follistatin-type molecules exhibit alternate modes of binding. J. Biol. Chem. 287, 1043–1053 (2012). PDB: 3SEK
Cash, J. N., Rejon, C. A., McPherron, A. C., Bernard, D. J. & Thompson, T. B. The structure of myostatin:follistatin 288: insights into receptor utilization and heparin binding. EMBO J. 28, 2662–2676 (2009). PDB: 3HH2
POST-DOCTORAL ResearcherS
Robin Stamler 2005-2007
Lei Qian 2016-2017
Visiting Scholars
Alena Bruening 2021-2022
