Dr. John Richardson

Professor of Biochemistry; Chemistry Department Chair

Chemistry / Academic

Office:

IDEA Center 344

Mailbox:

61547

Phone:

903.813.2494

Education:

B.S., Texas Tech University
Ph.D., Penn State College of Medicine

Endowed Professorship:

The Richardson Chair for the STEM Teaching and Research Leadership Program

Faculty Bio:

I am a biophysical chemist and joined the Austin College faculty in 2008 after finishing a postdoctoral fellowship at UT Southwestern Medical Center supported through a grant from the Cystic Fibrosis Foundation. My primary teaching responsibilities are Introductory Chemistry, Biochemistry, and Biochemical Metabolism. Undergraduate students have been very active in all aspects of my research program. I chose to set up my research program at Austin College because of its focus on undergraduate education—getting students involved in authentic research at an early stage is critical to cultivating the next generation of critically thinking scientist and physicians who will lead us through this new millennium. My research interests are focused on elucidating and understanding the rules of protein folding, and on the thermodynamic aspects of protein misfolding. Current studies are directed at understanding the role of misfolding of beta-2 microglobulin with respect to dialysis related amyloidosis, as diseases induced by long term hemodialysis.

Recent Courses:

• Chem 101 – Mastering the Art of Chemical Cooking
• Chem 111 – General Chemistry 1
• Chem 112 – General Chemistry 2
• Sci 201 – Politics of the Scientific Method
• Chem 351 – Introduction to Biochemistry
• Chem 352 – Biochemical Metabolism
• January Term – Secrets in the Kitchen

Research Interests:

Proteins adopt one specific biochemically relevant conformation; this unique 3-dimensional structure specifies not only the protein function but how it interacts with other proteins and the components of the cell. When a protein folds incorrectly it is unable to perform its normal cellular functions. A secondary consequence is a toxic gain of function that is the hallmark of many protein misfolding maladies including Parkinson’s and Alzheimer’s disease. The link between protein misfolding and human disease make the study and understanding of the protein folding relationship between sequence and structure a critically important question to be addressed.

Dialysis related amyloidosis (DRA) is a protein misfolding disease associated with long term hemodialysis resulting in a toxic gain of function for b-2-microglobulin (b2m), a component of the major histocompatibility complex. b2m is a 99-residue protein with a classical immunoglobulin fold which can be expressed recombinantly. b2m is necessary for the cell surface expression of the major histocompatibility complex (MHC). When b2m is released from the MHC, it circulates in the sera until it is degraded in the kidney. Patients with long term kidney failure can have up to 10 fold more b2m in circulation than their healthy counterparts. DRA is characterized by accumulation of b2m deposits leading to severe joint pain and immobility. In end-stage patients, deposits have also been found localized in the GI tract and heart. Currently the only treatment for DRA includes filtration of amyloid. While filtration may remove large aggregates it does not stop the misfolded “seed” particles from reentering circulation and propagating disease.

Most of the current work on DRA focuses only on the formation of amyloid, with very little attention being given to the native state of b2m. In order to fully understand the misfolding events, the process must be viewed in the context of what constitutes the productive folding pathway for b2m. Understanding what constitutes the normal folding pathway will directly lead to an appreciation for how the misfolding events lead to the formation of amyloid. Rigorous biophysical characterization of b2m will provide a complete picture of the folding pathway and which amino acids are crucial to maintain the protein on a folding trajectory. Increasingly misfolded proteins are being linked to larger numbers of human diseases. Understanding the link between protein folding/misfolding makes this study of protein folding a critical interest to public health, as well as a scientific endeavor to identify the biophysical principles that drive the misfolding process.

Publications:

1. Kelynne E. Reed, D.P.A., Lance F. Barton, Stephanie L. Gould, Karla S. McCain, and John M. Richardson, Integrating Leadership Development Throughout the Undergraduate Science Curriculum. Journal of College Science Teaching, 2016. 45(5): p. 51-59.
2. Reed, K.E.; Richardson, J.M. “Using Microbial Genome Annotation as a Foundation for Collaborative Student Research.” Biochem. Mol. Biol. Education. 2013 41 (1):34-43.
3. Matos, M.F.; Xu, Y.; Dulubova, I.; Otwinowski, Z.; Richardson, J.M.; Tomchick, D.R.; Rizo, J.; Ho, A. “Autoinhibition of Mint1 Adaptor Protein Regulates Amyloid Precursor Protein Binding and Processing” PNAS 2012 Mar 6, 109(10): 3802-07
4. Hoelen, H., Kleizen, B., Schmidt, A., Richardson, J.M., Charitou, P., Thomas, P., Braakman, I., “The Primary Folding Defect of F508 CFTR Originates in NBD1 and Can Be Rescued within the Domain” PLoS One 2010 Nov 30;5(11):e15458.
5. Thibodeau P.H., Richardson J.M., Wang W., Millen L., Watson J., Mendoza J., Du K., Fischman S., Senderowitz H., Lukacs G.L., Kirk K., Thomas P.J. “The Cystic Fibrosis Causing Mutation DF508 affects Multiple Steps In Cystic Fibrosis Conductance Regulator Biogenesis” Journal of Biological Chemistry 2010 Nov 12;285(46):35825-35
6. Richardson, J.M., Lopez, M.M., and Makhatadze G.I. “Enthalpy of helix-coil transition: missing link in rationalizing the thermodynamics of helix-forming propensities” PNAS 2005; 102 (5); 1413-1418
7. Richardson, J.M., and Makhatadze, G.I. “Temperature dependence of the thermodynamics of helix-coil transition.” J Mol Biol 2004; 335: 1029-1037.
8. Ermolenko, D.N., Richardson, J.M., and Makhatadze, G.I. 2003. “Noncharged amino acid residues at the solvent-exposed positions in the middle and at the C terminus of the alpha-helix have the same helical propensity”. Protein Science 2003; 12: 1169-1176.
9. Richardson J.M.; Lemaire S.; Jacquot J.P. and Makhatadze G. I. “Difference in the mechanisms on the cold and heat induced unfolding of Thioredoxin h from Chlamydomonas reinhardtii : spectroscopic and calorimetric studies” Biochemistry, 2000, 39, 11154-11162.
10. Lemaire S.D., Richardson J.M., Goyer A., Keryer E., Lancelin J.M., Makhatadze G.I., Jacquot J.P. “Primary structure determinants of the pH- and temperature – dependent aggregation of thioredoxin. Biochimica Et Biophysica Acta 2000; 1476: 311-323.

Faculty Extras:

• Discovery Foundation Grant 2016 – 2019 “Using Spectroscopy to Probe Structure-Function Relationships Driven by Intermolecular Interactions: An Undergraduate Research Program to Prepare Students for their Futures”
• American Society for Biochemistry and Molecular Biology – Education Fellow Sigma Xi Member
  Protein Society Member
• Alpha Phi Omega National Co-ed Service Fraternity – Chapter Advisor
• Melon Digital Pedagogy Partner
• Melon Course Partnership Participant
• STAR Leadership Advisory Committee