Contact
- Phone: (412) 648-8533 Fax: (412) 648-9008
- ahinck@pitt.edu
Department
Structural BiologyAndrew P. Hinck, PhD
Professor and Co-Director Mol. Biophysics and Structural Biology Graduate Program
Personal Statement:
Website: http://hincklab.structbio.pitt.edu
Education
B.S. Chemistry, University of Puget Sound, Tacoma, WA, 1997
Ph.D. Biochemistry, University of Wisconsin, Madison, Madison, WI, 1993
Post doctoral, University of Wisconsin, Madison, WI, NIH Ruth Kirchenstein Fellow, 1993-1994
Post doctoral, National Institute of Dental Research, Bethesda, MD,1994-1997
Research
Short: Structural Biology of TGF-beta family signaling proteins
Long: In the Hinck laboratory, we are interested in utilizing the tools of structural biology to understand how the structure and dynamics of biological macromolecules engenders them with their extraordinary ability to specifically and selectively bind 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, Cryo-electron microscopy, 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 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 proteins of family to achieve their unique biological functions. In addition, we are interested in exploiting the unique adaptations our structural studies uncover to develop highly potent TGF-beta inhibitors for treatment of cancer.
Publications
Kim, S. K., Whitley, M., Krzysiak, T. C., Hinck, C. S., Taylor, A. B., Zwieb, C., Byeon, C-H., Zhou, X., Mendoza, V., López-Casillas, F., Furey, W., and Hinck, A. P. Structural adaptation in its orphan domain engenders betaglycan with an alternate mode of growth binding relative to endoglin, Structure, 27, 1427-1442 (2019).
Henen, M. A., Mahlawat,P., Zwieb, C., Kodali, R. B., Hinck, C. S., Hanna, R. D., Krzysiak, T. C., Ilangovan, U., Cano, K. E., Hinck, G., Vonberg, M., McCabe, M., and Hinck, A. P. TGF-b2 binds the betaglycan ZP domain on the concave surface of the extended finger region through three residues unique to TGF-b and Inhibin-a, J. Biol. Chem., 294, 3065-3080 (2019).
Johnston, C. J. C., Smyth, D. J., Kodali, R.B., Harcus, Y., Filbey, K.J., Hewitson, J.P., Kildemoes, A., Hinck, C.S., Ivens, Al, Kemter, A.M., Le Bihan, T., Soares, D., Anderton, S.M., Brenn, T., Wigmore, S.J., Woodcock, H., Chambers, R.C., Hinck, A. P., McSorley, H.J., and Maizels, R.M. Convergent evolution of a novel immunosuppressive mimic of mammalian TGF-β by an intestinal helminth parasite, Nature Communications, 8, 1741-1749 (2017).
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. An engineered TGF-b monomer that functions as a dominant negative to block TGF-b signaling, J. Biol. Chem, 292, 7173-7188 (2017).
Hinck A. P., Mueller, T. D., and Springer, T. A. Structural Biology and Evolution of the TGF-b family Cold Spring Harbor Perspectives in Biology, 8, a022103 (2017).