Department of Chemistry

Education

• BS, University of Nebraska, 1997
• Ph.D., University of Michigan, 2003
• Organic and Medicinal Chemistry, Fermentation Science

Interests and Expertise

I am particularly interested in how small organic molecules interact with biological systems, which ties together my research projects related to both medicinal/organic chemistry and fermentation science topics.

My most active current projects involve fermentation in some fashion. In our most expansive project, we are attempting to develop a method of "fingerprinting" varietal honeys use nuclear magnetic resonance (NMR) spectroscopy. The flavors and aromas of specific types of honeys are prized by makers of mead (honey wine), and are caused by specific organic chemicals transported by bees from the original floral source back to the hive along with the nectar. By developing a method for identifying the characteristic chemicals present in common honey varietals, we can provide a method for authenticating honey to ensure it is not counterfeit or adulterated with less desireable varietals. In a second project, we are also interested in the tracking of bitterness units (BU) in beer throughout the production process using a streamlined ultraviolet (UV) spectroscopy method that can be implemented parallel to the brewing process to allow for course corrections during a brewday.

My medicinal/organic research interests involve the isolation, design, and synthesis of small molecule inhibitors of biological systems. This part of my lab currently focuses on the development of inhibitors of plasminogen activator inhibitor-1 (PAI-1), a human protein implicated in thrombosis, atherosclerosis, and myocardial infarction. This project is in collaboration with Prof. Daniel Lawrence's group at the University of Michigan Medical School, and together we have successfully identified and investigated multiple novel scaffolds that have proven to be potent and specific inhibitors of PAI-1. Some of these inhibitors are related to naturally occurring polyphenolic compounds, such as those found in green tea, while others incorporate a hydrazide functional group to gain their potency. Currently we are working to develop analogs of these compounds that show improved characteristics in vivo.

Courses

• CHEM 371-373 Organic Chemistry
• CHEM 571 Advanced Organic Chemistry
• CHEM 572 Organic Spectroscopy
• FERM 101 Introduction to Fermentation Science
• FERM 102 Introduction to Fermentation Science Laboratory
• FERM 421 Sensory Analysis of Fermented Products
• FERM 425 Fermented Beverage Production
• FERM 441 Fermentation Production Facilities

Publications and Presentations

• Torrente, D.; Su, E. J.; Fredriksson, L.; Warnock, M.; Bushart, D.; Mann, K.; Emal, C. D.; Lawrence, D. A. “Compartmentalized reactions of the plasminogen activator inhibotrs, PAI-1 and Nsp in ischemic stroke” Transl. Stroke Res. 2022, 13, 801-815. doi: 10.1007/s12975-022-00992-y
• Jílková, A.; Rubešová, P.; Fanfrlík, J.; Fajtová, P.; Řezáčová, P.; Brynda, J.; Lepšík, M.; Mertlíková-Kaiserová, H.; Emal, C. D.; Renslo, A. R.; Roush, W. R.; Horn, M.; Caffrey, C. R.; Mareš, M. “Druggable Hot Spots in the Schistosomiasis Cathepsin B1 Target Identified by Functional and Binding Mode Analysis of Potent Vinyl Sulfone Inhibitors” ACS Infect. Dis. 2021, 7, 1077-1088. https://doi.org/10.1021/acsinfecdis.0c00501
• Khoukaz, H. B.; Ji, Y.;  Braet, D. J.; Vadali, M.; Abdelhamid, A. A.; Emal, C. D.; Lawrence, D. A.; Fay, W. P. “Drug Targeting of Plasminogen Activator Inhibitor-1 Inhibits Metabolic Dysfunction and Atherosclerosis in a Murine Model of Metabolic Syndrome.” Arterioscler. Thromb. Vasc. Biol. 2020, 40, 1479-1490.
• Migliorini, M.; Li, S.; Zhou, A.; Emal, C. D.; Lawrence, D. A.; Strickland. D. K. "High affinity binding of plasminogen-activator inhibitor 1-complexes to LDL receptor-related protein 1 requires lysines 80, 88 and 207." Journal of Biological Chemistry, 2019, 295, 212-222.
• Reinke, A. A.; Li, S.; Warnock, M.; Shaydakov, M. E.; Guntaka, N. S.; Su , E. J.; Diaz, J. A.; Emal, C. D.; Lawrence, D. A. "Dual-reporter high-throughput screen for small-molecule in vivo inhibitors of plasminogen activator inhibitor type-1 yields a clinical lead candidate." Journal of Biological Chemistry, 2019, 294, 1464-1477.
• Li, S.-H.; Reinke, A. A.; Sanders, K. L.; Emal, C. D.; Whisstock, J. C.; Stuckey, J. A.; Lawrence, D.A. "Mechanistic characterization and crystal structure of a novel small molecule inactivator bound to plasminogen activator inhibitor-1." Proc. Natl. Acad. Sci. USA, 2013, 110, E4941–E4949.
• El-Ayache, N. C.; Li, S.-H.; Warnock, M.; Lawrence, D. A.; Emal, C. D. "Novel bis-arylsulfonamides and aryl sulfonimides as inactivators of plasminogen activator inhibitor-1(PAI-1)" Bioorganic and Medicinal Chemistry Letters, 2010, 20, 966–970.
• Cale, J. M.; Li, S.-H.; Warnock, M.; Su, E. J.; North, P. R.; Sanders, K. L.; Puscau, M. M.; Emal, C. D.; Lawrence, D. A. "Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1" Journal of Biological Chemistry, 2010, 285, 7892-7902.

Professional Affiliations

• American Chemical Society
• Certified Cicerone®
• American Society of Brewing Chemists
• Master Brewers Association of the Americas