Andrew P. Hinck
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Phone (412) 648-8533
Fax (412) 648-9008

University of Pittsburgh
1035 Biomedical Science Tower 3


Andrew Hinck

Professor, Department of Structural Biology
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.

Education & Training

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


Representative Publications

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: 18243107

Active Grants


Ligand-Receptor Interactions in the TGF-beta Superfamily
National Institutes of Health
Pathogenesis of vascular malformations in hereditary hemorrhagic telangiectasia: from disease mechanism to new therapies
07/01/2017 - 6/30/2021
Department of Defense Peer Reviewed Medical Research Program
Focused Program Award
Interaction between blood flow and ALK1 signaling in AVM development
04/01/2017 - 03-31-2021
National Institutes of Health

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

PITTSBURGH, May 29, 2013 – A team led by researchers at the University of Pittsburgh School of Medicine has described for the first time the 4-million-atom structure of the HIV’s capsid, or protein shell. The findings, highlighted on the cover of the May 30 issue of Nature, could lead to new ways of fending off an often-changing virus that has been very hard to conquer.
Scientists have long struggled to decipher how the HIV capsid shell is chemically put together, said senior author Peijun Zhang, Ph.D., associate professor, Department of Structural Biology, University of Pittsburgh School of Medicine.
“The capsid is critically important for HIV replication, so knowing its structure in detail could lead us to new drugs that can treat or prevent the infection,” she said. “This approach has the potential to be a powerful alternative to our current HIV therapies, which work by targeting certain enzymes, but drug resistance is an enormous challenge due to the virus’ high mutation rate.”
Previous research has shown that the cone-shaped shell is composed of identical capsid proteins linked together in a complex lattice of about 200 hexamers and 12 pentamers, Dr. Zhang said. But the shell is non-uniform and asymmetrical; uncertainty remained about the exact number of proteins involved and how the hexagons of six protein subunits and pentagons of five subunits are joined. Standard structural biology methods to decipher the molecular architecture were insufficient because they rely on averaged data, collected on samples of pieces of the highly variable capsid to identify how these pieces tend to go together.
Instead, the team used a hybrid approach, taking data from cryo-electron microscopy at an 8-angstrom resolution (a hydrogen atom measures 0.25 angstrom) to uncover how the hexamers are connected, and cryo-electron tomography of native HIV-1 cores, isolated from virions, to join the pieces of the puzzle. Collaborators at the University of Illinois then used their new Blue Waters supercomputer to run simulations at the petascale, involving 1 quadrillion operations per second, that positioned 1,300 proteins into a whole that reflected the capsid’s known physical and structural characteristics.
The process revealed a three-helix bundle with critical molecular interactions at the seams of the capsid, areas that are necessary for the shell’s assembly and stability, which represent vulnerabilities in the protective coat of the viral genome.
“The capsid is very sensitive to mutation, so if we can disrupt those interfaces, we could interfere with capsid function,” Dr. Zhang said. “The capsid has to remain intact to protect the HIV genome and get it into the human cell, but once inside it has to come apart to release its content so that the virus can replicate. Developing drugs that cause capsid dysfunction by preventing its assembly or disassembly might stop the virus from reproducing.”
The project was funded by National Institutes of Health grants GM082251, GM085043 and GM104601 and the National Science Foundation.
“By using a combination of experimental and computational approaches, this team of investigators has produced a clearer picture of the structure of HIV’s protective covering,” said the National Institutes of Health’s Michael Sakalian, Ph.D., who oversees this and other grants funded through an AIDS-related structural biology program. “The new structural details may reveal vulnerabilities that could be exploited by future therapeutics.”
Co-authors include Gongpu Zhao, Ph.D., Xin Meng, Ph.D., Jiying Ning, Ph.D., Jinwoo Ahn, Ph.D., and Angela M. Gronenborn, Ph.D., all of the University of Pittsburgh; Juan R. Perilla, Ph.D., and Klaus Schulten, Ph.D., of the University of Illinois at Urbana-Champaign; Ernest L. Yufenyuy, Ph.D., and Christopher Aiken, Ph.D., of Vanderbilt University School of Medicine; and Bo Chen, Ph.D., of theUniversity of Central Florida, in Orlando.

Original Link:

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.

Congratulations Karl!