Scott Pegan, Ph.D.

Pharmaceutical and Biomedical Sciences
Associate Professor
Interim Director, Center for Drug Discovery

Pharmaceutical and Biomedical Sciences

Education

PhD Chemistry and Biochemistry, University of California at San Diego

M.S. Chemistry and Biochemistry, University of California at San Diego

B.S. Molecular Biology- Biochemistry, University of California at Santa Barbara

Honors, Awards, and Achievements

University Council Executive Committee Chair for the University of Georgia (2017-2018)

University System of Georgia Faculty Council Chair Elect (2017-2018) prior to being Chair (2018-2019)

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)

Major, Biochemist; United States Medical Research Institute of Chemical Defense, United States Army Reserve

United States Army Operation Iraqi Freedom Combat Veteran (2004-2005)

Affiliations
Research Interests

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 therapeutics for nerve and pesticide agent poisoning

The potential threat of an intentional release of chemical nerve agents along with thousands of fatalities in developing countries every year caused by pesticide poisoning has made treatments for these types of poisonings a persistent focus for therapeutic intervention. Chemical nerve agents, as well as many pesticides, rely on the same organophosphate core to inhibit acetylcholinesterase activity. Using various biochemical and biophysical methods we intent to generate novel biologic and small molecule molecules of therapeutic value in order to address the current medical shortcomings.

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.

Selected Publications

Kim S, Alsaidn OA, Goodwin O, Li Q, Han Z, Bai A, Ablers T, Beharry Z, Zheng G, Norris JS, Szulc ZM, Alicja Bielawska, Lebedyeva I, Pegan SD, Cai H.*, Blocking Myristoylation of Src Inhibits Its Kinase Activity and Suppresses Prostate Cancer Progression., Cancer Res. 2017 Oct 16. PMID: 29038344 (IF2016=9.122)

Daczkowski CM, Octavia O, Dzimianski JV, Farhat JJ, Pegan SD.*, Structurally guided removal of deISGylase biochemical activity from papain-Like protease originating from the Middle East Respiratory Syndrome Virus, J Virol. 2017 Nov 14;91(23) Epub: 2017 Sep 20. PMID: 28931677 (IF2016=4.663)

Scholte FEM, Zivec M, Dzimianski JV, Deaton M, Spengler SR, Welch SR, Nichol ST, Pegan SD, Spiropoulou CF, Bergeron E.*, Crimean-Congo Hemorrhagic Fever Virus Suppresses Innate Immune Responses via a Ubiquitin and ISG15 Specific Protease. Cell Rep. 2017 Sep 5;20(10):2396-2407. PMID: 28877473 (IF2016=8.282)

Daczkowski CM, Dzimianski JV, Clasman JR, Goodwin O, Mesecar AD, Pegan SD*., Structural insights into the interaction of coronavirus papain-like proteases and interferon-stimulated gene product 15 from different species. J Mol Biol. 2017 Apr 21. PMID: 28438633 (IF2016=4.632)

Daczkowski CM, Dzimianski JV, Clasman JR, Goodwin O, Mesecar AD, Pegan SD., Structural insights into the interaction of coronavirus papain-like proteases and interferon-stimulated gene product 15 from different species. J Mol Biol. 2017 Apr 21. PMID: 28438633

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. [Selected as a featured article for its issue]

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

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 Ab42 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.

Full list of publications.

Grant Support

“Origin of the innate immunity suppression caused by nairovirus’ protease activity,” Scott Pegan (PI), NIH, 1R01AI109008-01, NOV2014-OCT2018.

“Role of the viral ovarian domain protease in PRRSV pathogenesis,” Scott Pegan (Co-I), National Pork Board, OCT2015-SEP2017.