University of Pittsburgh
Andrew Hinck’s research is focused on using the tools of structural biology to understand how the structure and dynamics of biological macromolecules engenders them with their extraordinary ability to specifically and seletively bind relevant partners and assemble into functional complexes. In my laboratory, we rely heavily on NMR spectroscopy as a tool for studying the structure and dynamics of biological macromolecules, but we also use X-ray crystallography and other accompanying biophysical tools, such as isothermal titration calorimetry (ITC), surface plasmon resonance (SPR), and fluorescence spectroscopy. In addition, my laboratory employs cell-based studies to assess the significance of key molecular features we have identified in a cellular context. In my laboratory, a major area of emphasis is studying signaling proteins and receptors of the TGF-beta family, a highly diversified signaling family, with representative family members in both in invertebrates and vertebrates. In our research, we are interested in deciphering the molecular adaptations that the signaling proteins, single-pass transmembrane receptors, downstream effectors, and multitude of extracellular and intracellular modulators have acquired that enable the more than thirty proteins of family to achieve their unique biological functions. In addition, we are interested in exploiting the unique adaptations our structural studies uncovered to develop highly potent TGF-beta inhibitors for treatment of cancer or fibrosis. If you are interested in learning more my research and my research group, you can learn more by exploring the
Hinck laboratory website.
University of Puget Sound, Tacoma, WA, USA
Magna Cum Laudem, 1987 in Chemistry
University of Wisconsin, Madison, WI, USA
Ph.D., 1993 in Biochemistry, Advisor: John L. Markley
University of Wisconsin, Madison, WI, USA
NIH Ruth Kirchenstein Postdoctoral Fellow, Advisor: Laura L. Kiessling
National Institute of Dental Research, Bethesda, Md
NIH IRTA and Staff Fellow, Advisor: Dennis A. Torchia
Awards & Honors
2011 UT Health Sci. Ctr. San Antonio, Cancer Therapy Res. Ctr. Discovery of the Year Award
2011 U. Wisconsin-Madison, Dept of Biochemistry, Everson Lecturer
2008 Stanford Syn. Rad. Light Source Research Highlight
1994 NIH NRSA Kirchenstein Postdoctoral Fellowship
1993 U. Wisconsin-Madison, Dept. Biochemistry Sigrid Leirmo Memorial Award
1992 U. Wisconsin-Madison, Sigma Xi Outstanding Thesis Award
Kim, S-K. K., Barron, L., Hinck, C. S., Petrunak, E. M., Cano, K. E., Thirangala, A., Iskra, B., Brothers, M., Vonberg, M., Leal, B., Richter, B., Kodali, R., Taylor, A. B., Du, S., Barnes, C. O., Sulea, T., Calero, G., Hart, P. J., Hart, M. J., Demeler, B., and Hinck, A. P. (2017) An engineered TGF-b monomer that functions as a dominant negative to block TGF-b signaling, J. Biol. Chem. (in press). PMID: 28228478
Villarreal, M. M., Kim, S-K., Barron, L., Kodali, R., Baardsnes, J., Hinck, C. S., Henen, M. A., Pakhomova, O., Mendoza, V., O’Connor-McCourt, M. D., Lafer, E. M., López-Casillas, F., and Hinck, A. P. (2016) Binding properties of the TGF-beta co-receptor betaglycan: proposed mechanism for potentiation of receptor complex assembly and signaling, Biochemistry, 55, 68800-6896. PMID: 27951653
Hinck A. P., Mueller, T. D., and Springer, T. A. (2016) Structural Biology and Evolution of the TGF-b family Cold Spring Harbor Perspectives in Biology, (in press). PMID: 27638177
Huang, T., Schor, S. L., Hinck, A. P., (2014) “Biological activity differences between TGF-β1 and TGF-β3 correlate with differences in the rigidity and arrangement of their component monomers” Biochemistry, 53, 5737-5749. PMID: 25204799
Huang, T., David, L., Mendoza, V., Yang, Y., Villarreal, M., De, K., Sun, L., Fang, X., López-Casillas, F., Wrana, J.L., and Hinck, A. P. (2011) “TGF-β signaling is mediated by two autonomously functioning TbRI:TbRII pairs”, EMBO J., 30, 1263-1276. PMID: 21423151.
Groppe, J., Hinck, C. S., Samavarchi-Tehrani, P., Zubieta, C., Schuermann, J., Taylor, A., Schwarz, P., Wrana, J., & 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. PMID: 18243111
See also the preview by J. Massagué entitled “A very private TGF-β receptor embrace” (Mol. Cell, 29, 149-150) and research highlight by N. Gough in Science STKE (Science Signalling, 1, 46). PMID: 18243107Active Grants
Inhibition of the tumor-promoting effects of TGF-beta in advanced prostate cancer
National Institutes of Health
Pitt-led Team Describes Molecular Detail of HIV’s Inner Coat, Pointing the Way to New Therapies
Original Link: http://www.upmc.com/media/NewsReleases/2013/Pages/pitt-team-molecular-HIV-detail-new-therapies.aspx
Karl Debiec was awarded the Andrew Mellon Predoctoral Fellowship for the 2014-2015 academic year.
These fellowships are awarded to students of exceptional promise and ability when they have advanced to the dissertation stage.
EAS New Faculty Award in NMR Spectroscopy
Patrick van der Wel is an assistant professor in the Department of Structural Biology of the University of Pittsburgh School of Medicine. He received his undergraduate degree in Chemistry at Utrecht University in the Netherlands, and his PhD degree in Chemistry & Biochemistry at the University of Arkansas, in Fayetteville. He then pursued his postdoctoral research in the lab of Professor Robert Griffin at the Massachusetts Institute of Technology, before joining the faculty of the University of Pittsburgh in 2008.
Dr. van der Wel’s scientific interests focus on the development and application of solid-state NMR spectroscopy for studies of biological systems. During his undergraduate and graduate research, he applied solid-state NMR to address basic biophysical and structural processes that govern protein-lipid interactions. Specifically, he probed the molecular interplay between hydrophobic mismatch and transmembrane helix tilt and how proteins or peptides can modulate membrane curvature.
His postdoctoral research in the Griffin lab centered on magic-angle-spinning methods that permitted him to address an expanded array of biological and biophysical questions. His work focused on both the methodological aspects of solid-state NMR and the applications to determine protein structure and dynamics, including the application of low-temperature dynamic nuclear polarization (DNP) to amyloid-related samples and on the effect of low temperatures on protein dynamics and solid-state NMR spectra. Using various magic angle spinning methods, Dr. van der Wel characterized structure and in particular, the internal conformations, of amyloid fibrils.
At the University of Pittsburgh, his lab uses an array of solid-state NMR measurements of site-specific structure as well as dynamics to further our understanding of protein-membrane interactions and amyloid formation. A particular focus has been on the aggregation process associated with polyglutamine expansion in Huntington’s disease and related disorders. Dr. van der Wel has published more than 30 papers, covering topics ranging from amyloid formation and structure, to membrane biophysics, to low-temperature DNP, to magic angle spinning and oriented-membrane solid-state NMR spectroscopy.
The award, sponsored by Agilent Technologies, Inc., will be presented on Tuesday, November 19th from 2 to 5 pm.