Matthew Gage

Expertise

Protein Structure/Function, biophysics, Spectoscopy, Bioinformatics

Research Interests

My research is focused on understanding protein function at a molecular level. I am interested in systems that are unique or break the "rules," such as disordered proteins. Our main focus is in the muscle protein titin and other proteins that interact with titin and we use a range of biophysical and bioinformatics tools to try to understand the complex interplay between the various proteins in the muscle.

Education

• Ph.D.: Biochemistry and Molecular Biology, (2001), Purdue University - Indiana, USA
  Dissertation/Thesis Title: Interaction of the Virally Encoded Fungal Toxin KP4 with Calcium Channels (Advisor : Thomas J. Smith, Ph.D.).
• BS: Chemistry, (1996), University of Wyoming - Wyoming, USA
• BS: Molecular Biology with Honors, (1996), University of Wyoming - Wyoming, USA

Selected Awards and Honors

• Dean's List - University of Wyoming
• NIH Biophysics Training Grant (2001) - Purdue University
• Honor Book, Department of Molecular Biology. (1996) - University of Wyoming
• Outstanding Student, Department of Chemistry (1996) - University of Wyoming
• NSF REU Fellow, Department of Chemistry (1995) - University of Wyoming

Selected Publications

• Shechter, S., S. Ya'ar Bar, H. Khattib, M.J. Gage, and D. Avni, Riok1, A Novel Potential Target in MSI-High p53 Mutant Colorectal Cancer Cells. Molecules, 2023. 28(11), 4452. DOI: 10.3390/molecules28114452.
• Hettige, P., U. Tahir, K. Nishikawa, and M. Gage, Transcriptomic profiles of muscular dystrophy with myositis (mdm) in extensor digitorum longus, psoas, and soleus muscles from mice. BMC Genomics, 2022. 23(1): p. 1-17.
• Hettige, P., D. Mishra, H. Granzier, K. Nishikawa, and M.J. Gage, Contributions of Titin and Collagen to Passive Stress in Muscles from mdm Mice with a Small Deletion in Titin's Molecular Spring. International Journal of Molecular Sciences, 2022. 23(16): p. 8858.
• Manukian, S., G.E. Lindberg, E. Punch, S.P.D. Mudiyanselage, and M.J. Gage, pH-Dependent Compaction of the Intrinsically Disordered Poly-E Motif in Titin. Biology, 2022. 11(9): p. 1302.
• Sundar, S., B. Rimkus, P.S. Meemaduma, S. deLap, N. LaFave, A.W. Racca, P. Hettige, J. Moore, M. Gage, A. Shehaj, and N. Konow, Bridging the muscle genome to phenome across multiple biological scales. J Exp Biol, 2022. 225(7), jeb243630. DOI: 10.1242/jeb.243630.
• Dassanayake Mudiyanselage, S.P. and M.J. Gage, Regulation of Poly-E Motif Flexibility by pH, Ca(2+) and the PPAK Motif. Int J Mol Sci, 2022. 23(9), 4779. DOI: 10.3390/ijms23094779.
• Tsiros, C., Punch, E., Schaffter, E., Apel, S., Gage, M.J., “Identification of the domains within the N2A region of titin that regulate binding to actin,” Biochemical and Biophysical Research Communications, (2022).
• Kelly, C. & Gage M.J., “Protein Unfolding: Denaturant vs. Force” Biomedicines (2021).
• Kelly, C.M., Pace, N., Gage, M.J., Pfuhl, M “Solution NMR structure of titin N2A region Ig domain I83 and its interaction with metal ions” Journal of Molecular Biology, (2021)
• Putra, C., Konow, N., Gage, M.J., York, C.G., Mangano, K.M “Protein Source and Muscle Health in Older Adults: A Literature Review” Nutrients, (2021)
• McEntire, K.D., Gage, M., Gawre, R., Hadfield, M.G., Hulshof, C., Johnson, M.A., Levesque, D.L., Segura, J., Pinter-Wollman, N “Understanding Drivers of Variation and Predicting Variability Across Levels of Biological Organization.” Integrative and Comparative Biology, (2021)
• Premawardhana, D.M.S., Zhang F., Xu J., Gage M.J “The Poly-E motif in Titin's PEVK region undergoes pH dependent conformational changes” Biochemistry and Biophysics Reports, (2020)
• Hettige, P., Tahir U., Nishikawa K.C., Gage M.J “Comparative analysis of the transcriptomes of EDL, psoas, and soleus muscles from mice” BMC Genomics, (2020)
• Kelly, C.M., Manukian S., Kim E., Gage M.J “Differences in stability and calcium sensitivity of the Ig domains in titin's N2A region” Protein Science, (2020)
• Nishikawa, K., Dutta, S., DuVall, M., Nelson, B., Gage, M.J., Monroy, J “Calcium-dependent titin-thin filament interactions in muscle: observations and theory” Journal of Muscle Research and Cell Motility, (2019)
• Dutta, S., C. Tsiros, S.L. Sundar, H. Athar, J. Moore, B. Nelson, M.J. Gage, K. Nishikawa “Calcium increases titin N2A binding to F-actin and regulated thin filaments” Scientific Reports, (2018)
• Tiffany, H., K. Sonkar, M.J. Gage “The Insertion Sequence of the N2A Region of Titin Exists in an Extended Structure with Helical Characteristics” Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, (2017)
• Done, A.J., M.J. Gage, N.C. Nieto, T. Traustadottir “Exercised-induced Nrf2 signaling is impaired in aging” Free Radical Biology and Medicine, (2016)
• Purohit, R., B. G. Fritz, J. The, A. Issaian, A. Weichsel, C. L. David, E. V. Campbell, A. C. Haurath, L. Rassouli-Taylor, E. D. Garcin, M. J. Gage, W. R. Montfort “YC-1 Binding to the Beta Subunit of Soluble Guanylyl Cyclase Overcomes Allosteric Inhibition by the Alpha Subunit.” Biochemistry, (2014)
• Ma, W. K., R. Hendrix, C. Stewart, E. V. Campbell, M. Lavarias, K. Morris, S. Nichol, M.J. Gage “FlgM proteins from different bacteria exhibit different structural characteristics.” Biochimica et Biophysica Acta (BBA) - Proteins & Proteomics, (2013)
• Heintze, E., C. Aguilera, M. Davis, A. Fricker, Q. Li, J. Martinez, M.J. Gage “Exposure to uranium complexes results in upregulation of p53 mediated pathways.” Journal of Inorganic Biochemistry, (2011)
• Molloy, R.G., W. K. Ma, A. C. Allen, K. Greenwood, L. Bryan, R. Sacora, L. Williams, M. J. Gage “Aquifex aeolicus FlgM protein does not exhibit the disordered character of the Salmonella Typhimurium FlgM protein.” Biochimica et Biophysica Acta (BBA) - Proteins & Proteomics, (2010)
• Webber, T. M., A. C. Allen, W.K. Ma, R.G. Molloy, C. N. Kettelkamp, C.A. Dow, M.J. Gage "Conformational detection of p53's oligomeric state by FlAsH Fluorescence." Biochemistry & Biophysics Research Communications, (2009)
• Webber, T., S. Gurung, J. Saul, T. Baker, M. Spatara, M. Freyer, A.S. Robinson, M.J. Gage. "The C-terminus of the P22 tailspike protein acts as an independent oligomerization domain for monomeric proteins." Biochemistry Journal, (2009)
• Gage, M.J., J.L. Zak, and A.S. Robinson “Three Amino Acids that are Critical to Formation and Stability of the P22 Tailspike Trimer.” Protein Science , (2005)
• Gage M.J., B.L. Lefebvre, A.S. Robinson, Determinants of P22 Tailspike Folding and Aggregation., in Misbehaving Proteins: Protein (Mis)Folding, Aggregation, and Stability, eds R. Murphy and A. Tsai, ACS press, invited review.
• Lefebvre, B.L., N.K. Comolli, M.J. Gage, A.S. Robinson “Pressure Dissociation Studies Provide Insight Into Oligomerization Competence of Temperature-Sensitive Mutants of P22 Tailspike,” Protein Science4, (2004)
• Lefebvre, B.L., M.J. Gage, A.S. Robinson “Maximizing Recovery of Native Protein from Aggregates by Optimizing Pressure Treatment,” Biotechnology Progress, (2004)
• Gage, M.J., A. S. Robinson “C-Terminal Hydrophobic Interactions Play a Critical Role in Oligomeric Assembly of the P22 Tailspike Trimer” Protein Science (2003)
• Gage, M.J., S. G. Rane, G. H. Hockerman, T. J. Smith “The Virally Encoded Fungal Toxin KP4 Specifically Blocks L-Type Voltage Gated Calcium Channels.” Molecular Pharmacology, (2002)
• Gage, M.J., J. Bruenn, M. Fischer, D. Sanders, T. J. Smith “KP4 Fungal Toxin Inhibits Growth in Ustilago maydis by Blocking Calcium Uptake.” Molecular Microbiology, (2001)

Selected Presentations

• “Impacts of pH Fluctuations on the Structure and Binding Interactions of Titin” Invited Seminar, New England Muscle and Molecular Motors Meeting, June 20, 2024
• “Deciphering the Role of Titin’s Ig Domains” Invited Seminar, King’s College, London, UK, November 7, 2023
• “Deciphering the Role of Titin’s Ig Domains” Invited Seminar, CINC, Madrid, Spain, November 3, 2023
• “Small Changes with Big Effects: Lessons Learned from the Structure of Titin” Invited Seminar, Wichita State University, September 6, 2023
• “Conformational Dynamics in Titin’s PEVK Region” Invited Seminar, University of Calgary, August 24, 2023
• “Small Changes with Big Effects: Lessons Learned from the Structure of Titin” Invited Seminar, University of Vermont, May 8, 2023
• “Deciphering the function of binding interactions involving the N2A region of titin: small interactions with large implications” Invited Seminar, Purdue University, April 29, 2022
• “Pooled Specimen Testing at UMass Lowell for a Faster Return to Campus Life” Data Innovations Webinar, May 4, 2021
• “Titin: A Giant in the Protein Field” Invited Seminar, Mount Holyoke University, February 22, 2019
• “Titin: A Giant in the Protein Field” Invited Seminar, Rhode Island College, February 21, 2019
• “Understanding how the Structure of Titin’s N2A Region Drives Function in Active Muscles” Invited Seminar, Clark University, October 26, 2018
• “Varying Stability of the Immunoglobulin Domains in Titin’s N2A Region” Invited Seminar, 47th European Muscle Conference, August 31, 2018
• “Exploring the Relationship between Splicing and Titin Function” Invited Seminar, Shriners Hospital, June 1, 2017
• “Engineering Elasticity: How Changes in the Structure of Titin Modulates Muscle Function” Invited Seminar, Tulane University, February 16, 2017
• “Exploring the Role of the N2A Region of Titin in Skeletal Muscle Function” Invited Seminar, Bridgewater State, October 21, 2016
• “Exploring the Role of the N2A Region of Titin in Skeletal Muscle Function” Invited Seminar, Boston University, April 19, 2016
• “Intrinsically Disordered Proteins: Finding Function in the Absence of Structure” Invited Seminar, University of New Hampshire, March 25, 2016
• Characterization of the intrinsically Disordered Region of Soluble Guanylate Cyclase Aplha-1 Subunit" poster, Candice V. Benally, Parul Singh, and Matthew Gage, February 2014, Biophysical Society Annual Meeting. - Poster and Seminar Presentations, February 2014 - San Francisco, CA
• Structural Studies on the N2A-IS Region of Titin poster, Kanchan Sonkar, Holly Tiffany, and Matthew Gage, February 2014, Biophysical Society Annual meeting, San Francisco, CA." - Poster and Seminar Presentations, February 2014
• Intrinsically Disordered Proteins: Understanding protein Function in the Absence of Structure - Seminar Presentations, February 2013 - Fargo, ND
• Exploring the World of Intrinsically Disordered proteins" Matthew Gage, January 2013, IMSD Regional Meeting". - Invited Talk, January 2013 - Arizona
• Developing Inhibitors for E. Coli tryptophan Synthase and Indole -3- Glyserol Phosphate Synthase Utilizing in vitro and in silico techniques - Poster, August 2012 - San Diego, CA
• Characterizing the Structure and Function of Truncations from the Anti-Sigma Factor FlgM from Aquifex aeolicus - Poster and Talk, August 2012 - San Diego, CA
• - Structural Characterization of the Unique Sequence Region from the N2A Domain of Titin, August 2012 - San Diego, CA
• Thrombospondin-1 binding to CD 47 in the Regulation of Nitric Oxide Signaling, , August 2012 - San Diego, CA
• Determining the Effects of various Crowding Agents on eGEP to Model Folding within the Cell, Poster, Amber Enriquez and Matthew Gage . - Poster, July 2011 - Boston, MA
• Developing Inhibitors for Tryptophan Synthase Utilizing in Vitro and in Silico Studies was done by Holly Tiffany and Matthew Gage . - Poster, July 2011 - San Diego, CA
• Development of Novel inhibitors of Indole glycerol -3-Phosphate, was done by Andrew Allen, Dorothy Kampf and Matthew Gage. - Poster, July 2011 - Boston, MA
• Assessing the Degree of Disorder in Homologous FlgM proteins, Poster and Talk was done by Rachel Brackett, Wai kit ma and Matthew Gage. - Poster and Talk, July 2011 - Boston, MA
• Assessing Various Ways to Mimic the Cellular Environment , was successfully done by Avery Fricker, Chad park and Matthew Gage. - Poster and Talk, July 2011 - Boston ,MA
• Aquifex aeolicus FlgM protein exhibits a temperature dependent disordered nature - poster, July 2010 - San Diego, CA
• Designing novel antimicrobial compounds to inhibit unexplored metabolic pathways,'' Poster, Andrew Allen, Samuel Gilmore, Rhett Molloy, Allison Grace, Jason McCabe, Cindy Browder, Matthew Gage", was done in July 2010. - Poster, July 2010 - San Diego, CA
• Exploring conformational changes associated with binding of YC-1 to soluble guanylyl cyclase, Poster, Malia Davis, Camille Aguilera, Shauna Cooney, Matthew Gage, July 2010. - Poster, July 2010 - San Diego, CA
• Development of Inhibitors of the Methionine and Tryptophan Biosynthetic pathways, Seminar was done by Matthew J. Gage, DTRA TMT Quarterly Meeting in July 2010. - Seminar, July 2010
• Aquifex aeolicus FLgM Protein exhibits a temperature dependent disordered nature., February 2010 - San Francisco, CA.
• Applying Thermodynamics to Fragment -based Drug Development - Seminar and Poster publications, February 2010 - San Francisco, CA
• Assessing the degree of disorder in homologous FlgM proteins. - Seminar Presentations, February 2010 - San Francisco, CA.

Selected Contracts, Fellowships, Grants and Sponsored Research

• NIH R15 (Aug 2024 - Aug 2027)
• Understanding and Designing pH-Responsive Peptides in Confined Nanoscale Environments
• NSF (Aug 2022 – July 2025)
  IntBIO:Linking genome to phenome to understand the function of Masticatory Myosin
• NIST (Sept 2022 – Aug 2025)
  Peracetic Acid-Based Disinfectants (subcontract with Vuronyx Technologies)
• ChemGenes Corporation (2021)
  Testing RT-PCR probe set for COVID-19
• Contract with Hememics Biotechnologies, Inc (2020)
  Evaluating binding of CoV-2 peptides to antibodies
• NIH R15 (June 2019 – May 2022)
  Exploring the role of pH in protein conformational change and muscle elasticity
• Keck Foundation (July 2014 – Jan 2019)
  A New Twist on Muscle Contraction
• Improve musculoskeletal Health especially among the elderly (2018), Grant - IDEA Inter-Disciplinary Exchange & Advancement Initiative
  Lewis, E.S., Gage, M., Nugent, M.A., Mangano, K., Konow, N., Scribner-Maclean, M.
• UMOVE UMass MOVEment Research Center-Exploring the mechanics of movement and muscle function (2017), Grant - UMass President's Office Science and Technology Initiative
  Lewis, E.S., Gage, M.,