PhD Chemistry and Biochemistry, University of California
M.S. Chemistry and Biochemistry, University of California
B.S. Molecular Biology- Biochemistry, University of California
Regulation of the Human Innate Immune System
To gain a greater understanding of the mammalian innate immune response and how it is modulated, as well as develop new therapeutic templates for emerging diseases. Our on-going intent is to investigate the anti-viral type I response through the structural and kinetic study of proteases and ligases involved in the immune response signaling pathway. Through this research a better understanding of the role these proteins play in cellular regulation of the innate anti-viral immune response will occur. Currently, we are working with a model system from Crimean-Congo Hemorrhagic Fever virus (CCHFV), which in itself is a dangerous emerging pathogen exhibited by its recent deadly outbreaks in Turkey and India. Furthermore, CCHF has spread across Asia and Africa and is present particularly in the Middle East transmission. Danger to US was highlighted in 2009 by the death of a US Soldier serving in Afghanistan by CCHFV.
Discovery of new antibiotics for use against Tuberculosis
Tuberculosis (TB) is one of the most prevalent infections in the world, and a leader among the causes of mortality in developing countries. The World Health Organization estimates one third of the world’s population is infected with latent TB. With a rise in new cases of active TB and emergence of multidrug resistant strains, MDR-TB and XDR-TB, there is a strong need for development of antibiotics targeting novel pharmacological targets within Mycobacterium tuberculosis. One such drug target for TB is M. tuberculosis’ class II fructose 1,6-bisphosphate aldolase (MtFBA), which is required for bacterial survival and is non-existent in humans. Inhibitors have been developed for class II FBAs; however, they lack specificity and drug-like properties, preventing their translation into viable therapeutic leads. Optimization of these compounds has been historically hindered by a lack of MtFBA structural information and viable drug-like leads. Using the latest in Structural biology and drug discovery techniques, we intend to generate novel chemical compounds that have potent anti–bacterial features for therapeutics targeting TB and other pathogenic bacteria.
- “Origin of the innate immunity suppression caused by nairovirus’ protease activity,” Scott Pegan (PI), NIH, 1R01AI109008-01, NOV2014-OCT2018.
- “Molecular probes for a vOTU from CCHFV using a fluorogenic peptide,” Scott Pegan (PI), NIH, R03 MH097507-01A1, SEP2012-AUG2015.
- “Porcine Epidemic Diarrhea Virus (PEDV) and Porcine Delta Coronavirus (PDCoV) Protease Function and Modification to Improve Swine Innate Immunity,” Scott Pegan (PI), USDA, 58-5030-5-034, DEC2014-NOV2016.
- “Role of the viral ovarian domain protease in PRRSV pathogenesis,” Scott Pegan (Co-I), National Pork Board, OCT2015-SEP2017.
- Kamen Award for Best Dissertation in Biology & Chemistry, University of California, San Diego (June, 2006)
- NIH Training Grant on Molecular Biophysics Training Fellow (July, 2003 – June 2006)
- Travel Scholarship & Conference Poster Winner Keystone Symposia Structural Biology Meeting, Linking Cardiac Arrhythmia to Gene Defects (February, 2006)
- Captain, Biochemist; Scientific and Technology Advisor, United States Army Reserve
- United States Army Operation Iraqi Freedom Combat Veteran (2004-2005)
Deaton MK, Dzimianski JV, Daczkowski CM, Whitney GK, Mank NJ, Parham MM, Bergeron E, Pegan SD.*, Biochemical and structural insights into nairoviral deISGylases preference for interferon-stimulated-gene-product 15 originating from certain species. J Virol. 2016 Jul 13 PMID: 27412597.
Myslinski J, Height J, Pegan S*. (2016) Kinetics and Thermodynamics of Acetylcholinesterase Inhibition and Reactivation. (Unclassified Title), Edgewood Chemical Biological Center, US Army, Aberdeen Proving Grounds.
Ziverc M, Metcalfe MG, Albarino CG, Khristova ML, Guererro L, Pegan SD, Spiropoulou CF, Bergeron E.*, Crimean-Congo hemorrhagic fever virus-like particle system for rapid testing of protein compatibility and antivirals, PLoS Negl Trop Dis. (2015) Dec 1;9(12) PMID: 26625182
Daczkowski CM, Pegan SD*, Harvey SP*. Engineering the Organophosphorus Acid Anhydrolase Enzyme for Increased Catalytic Efficiency and Broadened Stereospecificity on Russian VX, Biochemistry. (2015) Oct 6. PMID:26418828
*Eisenmesser EZ, Capodagli GC, Armstrong G, Holliday MJ, Isern NG, Zhang F, and Pegan SD., Inherent dynamics within the Crimean-Congo Hemorrhagic fever virus protease are localized to the same region as substrate interactions,Protein Sci. (2015) Jan 6. PMID: 25564798
*Capodagli GC, Lee SA, Boehm KJ, Brady KM, Pegan SD., Structural and Functional Characterization of Methicillin-Resistant Staphylococcus aureus’s Class IIb Fructose 1,6-Bisphosphate Aldolase. Biochemistry. (2014) Dec 9; 53(48):7604-14. Epub 2014 Nov 21. PMID: 25390935
Capodagli GC, Sedhom WG, Jackson S, Ahrendt KA, Pegan SD*, A noncompetitive inhibitor for M. tuberculosis’s class IIa fructose 1,6-bisphosphate aldolase. Biochemistry, (2014) Jan 14; 53(1):202-13., Epub ahead of print on 2013 Dec 24
Capodagli GC, Deaton MK, Baker EA, Lumpkin RJ, Pegan SD*, Diversity of ubiquitin and ISG15 specificity amongst nairoviruses’ viral ovarian tumor domain proteases. J Virol. (2013), Apr vol. 87 no. 7 3815-3827, Epub ahead of print on 2013 Jan 23 [Selected as a featured article for its issue]
Pegan SD*, Rukseree K, Capodagli GC, Baker EA, Krasnykh O, Franzblau SG, Mesecar AD*., Active site loop dynamics of a class IIa fructose 1,6-bisphosphate aldolase from M. tuberculosis. Biochemistry (2013) Feb 5;52(5):912-25., Epub ahead of print on 2013 Jan
Park SK, Pegan SD, Mesecar AD, Jungbauer LM, Ladu MJ, Liebman SW*., Development and validation of a yeast high-throughput screen for inhibitors of A42 oligomerization. Dis Model Mech. (2011) Nov;4(6):822-31.
Capodagli GC, McKercher MA, Baker EA, Masters EM, Brunzelle JS, Pegan SD*, Structural analysis of a viral ovarian tumor domain protease from the Crimean-Congo Hemorrhagic Fever virus in complex with covalently bonded ubiquitin. J Virol. (2011) Apr;85(7):3621-30.