Green Distinguished Professor in Neuroscience
Vice Chair for Operation
Department of Neurobiology
5.212A Research Building 17
Route: 1069 |
Tel: (409) 772-1309 | Fax: (409) 747-2187 | afoberha@utmb.edu
Affiliation: Sealy Center for Structural Biology & Molecular Biophysics
Education and Training
PhD in Physiology & Biophysics, University of Chile, Santiago, Chile
Post-Doctoral in Physiology & Biophysics, University of Pennsylvania, Pennsylvania
Post-Doctoral in Physiology & Biophysics, Mayo Clinic, Rochester, Minneapolis
Research Interests
My research uncovers how proteins fold, respond to mechanical force, and preserve structural integrity inside living cells. By integrating single‑molecule biophysics, fluorescence‑based structural probes, and quantitative chaperone assays, my lab reveals the physical rules that govern protein stability, mechanotransduction, and cytoskeletal regulation. Our work connects fundamental protein‑folding mechanisms to the molecular origins of misfolding in human disease, offering a mechanistic view of how cells maintain order under constant mechanical stress.
A major thrust of our NIH funded research is decoding how muscle cells fold, protect, and repair the myosin motor 
domain—and why this system fails with age. We discovered that UNC 45 acts as a precision folding chaperone that captures and aligns the partially folded motor, while Hsp90 completes the folding and activation steps required for filament assembly or rapid recovery after stress. Collaborative work with Guy Benian (Emory University) revealed that aging selectively disrupts this UNC 45/Hsp90 cycle, reducing chaperone capacity and allowing misfolded or aggregation prone myosin to accumulate. This breakdown provides a powerful mechanistic explanation for age related sarcomere instability, declining contractile strength, and progressive muscle weakness.
Selected Publications
Oberhauser, A., Monck, J.R., Balch, W.E. and Fernandez, J.M. Exocytotic fusion is activated by Rab3 peptides. Nature 360:270-273, 1992.
Oberhauser, A.F., Marszalek, P.E., Erickson, H.P., and Fernandez, J.M. The molecular elasticity of tenascin, an extracellular matrix protein. Nature 393:181-185, 1998.
Qian, F., Wei, W., Germino, G.G., and Oberhauser, A.F. The Nanomechanics of Polycystin-1 extracellular region. J. Biol. Chem. 280(49):40723-30, 2005.
Bullard, B., Garcia, T., Benes., V., Leake, M., Linke, W., and Oberhauser, A.F. The Molecular Elasticity of the Insect Flight Muscle Proteins Projectin and Kettin. Proc. Natl. Acad. Sci. 103(12) 4451-4456, 2006.
Kaiser, C.M., Bujalowski, P.J., Ma, L., Anderson, J., Epstein, H.F. and Oberhauser, A.F. Tracking UNC-45 chaperone-myosin interaction with a titin mechanical reporter. Biophys J. 102(9):2212-9, 2012.
Bujalowski, .PJ., Nicholls, P. and Oberhauser, A.F. UNC-45B chaperone: the role of its domains in the interaction with the myosin motor domain. Biophys J. 107(3):654-61, 2014.
Nicholls, P., Bujalowski, P.J., Epstein, H.F., Boehning, D.F., Barral, J.M. and Oberhauser, A.F. Chaperone-mediated reversible inhibition of the sarcomeric myosin power stroke. FEBS Lett. 588(21):3977-81, 2014.
Bujalowski, P.J., Nicholls, P., Barral, J.M. and Oberhauser, A.F. Thermally-induced structural changes in an armadillo repeat protein suggest a novel thermosensor mechanism in a molecular chaperone. FEBS Lett. 589(1):123-30, 2015.
Bujalowski PJ, Nicholls P, Garza E, and Oberhauser AF. The central domain of UNC-45 chaperone inhibits the myosin power stroke. FEBS Open Bio. 2017 Dec 10;8(1):41-48, 2018.
Renn, J.P., S. Bhattacharyya, H. Bai, C. He, H. Li, A.F. Oberhauser, J.F. Marko, D.E. Makarov, and A. Matouschek. 2019. Mechanical unfolding of spectrin reveals a super-exponential dependence of unfolding rate on force. Sci Rep. 9:11101.
Goldson, T.M., K.L. Turner, Y. Huang, G.E. Carlson, E.G. Caggiano, A.F. Oberhauser, S.M. Fennewald, M.M. Burdick, and V.A. Resto. 2020. Nucleolin mediates the binding of cancer cells to L-selectin under conditions of lymphodynamic shear stress. Am J Physiol Cell Physiol. 318:C83-C93.
Qadota, H., J.C. Moody, L. Lesanpezeshki, T. Moncrief, D. Kitzler, P.D. Bhat, S.A. Vanapalli, A.F. Oberhauser, and G.M. Benian. 2020. A Region of UNC-89 (Obscurin) Lying between Two Protein Kinase Domains Is a Highly Elastic Spring Required for Proper Sarcomere Organization. J Mol Biol. 432:4799-4814.
Marszalek, P.E, and A.F. Oberhauser. 2020. Progress and Prospects of Single-Molecule Force Spectroscopy in Biological and Chemical Sciences. Journal of Cell Science 133
Gaziova, I., T. Moncrief, C.J. Christian, M. Villarreal, S. Powell, H. Lee, H. Qadota, M.A. White, G.M. Benian, and A.F. Oberhauser. 2020. Mutational Analysis of the Structure and Function of the Chaperoning Domain of UNC-45B. Biophysical Journal 119, 780–791, August 18, 2020
Moncrief, T., Christian, C. Gaziova, I., Miller, J., Qadota, H., Benian, G. M. & Oberhauser, A. F.; Mutations in conserved residues of the myosin chaperone UNC-45 result in both reduced stability and chaperoning activity. Protein Science, 2021 Nov;30(11):2221-2232
Valdebenito, S., Eugenin, E. and Oberhauser, A. SPR spectroscopic analysis of myosin binding to wild type and mutant UNC45B. MicroPubl Biol 2024 Feb 5. PMCID: PMC10884834.
Matheny, C.J., Qadota, H., Bailey, A.O., Valdebenito, S., Oberhauser, A.F., and Benian, G.M. The myosin chaperone UNC-45 has an important role in maintaining the structure and function of muscle sarcomeres during adult aging. Molecular Biology of the Cell, Vol. 35, No. 7. July 01, 2024