Scott G. Franzblau
Director, Institute for Tuberculosis Research
Albert Schatz Professor, College of Pharmacy - Pharmaceutical Sciences
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About
Overview:
Scott’s career path was driven by a desire to make a significant contribution to the treatment of those suffering from neglected infectious diseases. His work in this area began with the identification of conditions that would maintain viability/metabolic activity of unculturable Mycobacterium leprae for several weeks after harvest from the footpads of athymic mice. This, along with his finding that M. leprae rapidly oxidized palmitic acid together with a method for enriching for viable bacilli, led to development of the first validated in vitro drug susceptibility assays for M. leprae, employing 2 different radiorespirometric assays. This reduced the time for determining drug susceptibility from 1 year in the leprosy mouse model to 2-3 weeks. This in turn led to the identification of clarithromycin (in phase II trials for G+ infections at the time), sparfloxacin and fusidic acid as having potent activity. He then supervised the NIH-supported phase IIa clinical trials of these agents in lepromatous leprosy, all of which demonstrated clinical efficacy. In addition, Scott utilized the same radiorespirometric assay to assess bacteriological response in these trials and in an additional clinical trial of minocycline and demonstrated their correlation with the gold standard mouse assay. Clarithromycin is recommended in the WHO 2018 Leprosy Treatment Guidelines for rifampin or rifampin + fluoroquinolone-resistant leprosy.
After outbreaks of MDR TB in the U.S. in the 1980s, Scott turned his attention to TB and supervised the in vitro screening component of the NIH’s effort to quickly identify new TB drugs. After screening thousands of compounds in the state-or-the-art, but costly and low-throughput BACTEC 460 system, he developed the first microplate-based screening and MIC assay for TB, utilizing the resazurin-based Alamar Blue reagent. The “microplate Alamar Blue assay or MABA” would become adopted by most of the major institutions pursuing new TB drugs at the time and enabled the screening of tens of thousands of compounds. While fluorescent readouts were utilized in research institutions, he also demonstrated that the visual readout could be utilized in clinical, low-tech settings. Since the long treatment times required for cure were being linked to persistor sub-populations, Scott developed the first high-throughput compatible assay for non-replicating M. tuberculosis. The so-called “Low Oxygen Recovery Assay” continues to be utilized in the in vitro profiling of candidate compounds. His group has continued to develop higher throughput assays for the slow-growing TB bacillus which now include those for MBC, PAE and macrophage infection models.
At the time of development of the above assays, Scott developed a relationship with the Global Alliance for TB Drug Development (TBA), the leading non-profit organization that developed pretomanid and recently demonstrated the remarkable efficacy of the BPaL regimen in MDR and XDR-TB. His lab has been a major partner of the TBA since its inception in the year 2000. In that time, Scott’s group has provided IND-supporting data for 5 compounds that have entered clinical trial, two currently in phase I and two currently in phase II.
With the understanding that M. tuberculosis was not included in the original target panels during the heyday of soil microbe screening for new antibiotics, Scott reasoned that narrow spectrum, anti-TB compounds were likely missed during that time and he sought out partners with large actinomycete collections. Using a newer luxABCDE reporter, his group screened several hundred thousand extracts from a Korean collaborator and subsequently isolated and identified two cyclic peptides with potent activity, that targeted the essential ClpC1 component of the major protein degradation machinery. This led to a lead ID/optimization project within a NIH Centers for Excellence in Translational Research (CETR) in which his group has contributed natural products chemistry, semi-synthesis, in vitro and in vivo anti-TB assays, SPR analyses and structural biology. After four years, the synthetic component, led by the TBA (the prime recipient in this CETR), has compounds poised to be candidates for IND-enabling studies.
Throughout his career and enabled by the requisite resources, Scott has continued to offer his lab’s suite of in vitro and in vivo assays to evaluate candidate anti-TB compounds from any institute in the world and without charge to academics and other non-profits. His 300+ publications are largely a result of that collaborative spirit and commitment to the alleviation of neglected infectious diseases.
Research Interests:
1) New drug discovery for tuberculosis, non-tuberculous mycobacteria, Lyme Disease and ESKAPE pathogens
2) Antimicrobial assay development
3) Isolation of novel minor bioactive secondary metabolites
Teaching and Supervision
PDAT 6: Infectious Diseases (PHAR 506), 1/10/2022 – 4/29/2022
PDAT 6: Infectious Diseases (PHAR 506), 1/10/2022 – 4/29/2022
PSCI Ph.D. Thesis Research (PSCI 599), 8/23/2021 – 12/3/2021
PHAR 506 (PHAR 506), 2/24/2021 – 2/24/2021
Undergrad Res Exp MedChem&Pcog (PMMP 300), 1/14/2019 – 5/3/2019
Spec Project Med Chem &Pcog (PMMP 390), 1/9/2017 – 4/28/2017
Fund of Drug Action III (PHAR 333), 8/22/2016 – 12/2/2016
Fund of Drug Action III (PHAR 333), 8/22/2016 – 12/2/2016
Lab Tech in Pcog I (PMPG 590), 1/11/2016 – 4/29/2016
Selected Grants
Development of novel ClpC1 modulators targeting proteostasis for the treatment of M. tuberculosis, Global Alliance for TB Drug Development., 11/1/2024 - 11/9/2026, Obligated Amount: $208524; Anticipated Amount: $208524
Host-directed approaches to target granuloma pathways for treatment shortening in tuberculosis, Global Alliance for TB Drug Development., 9/30/2024 - 9/29/2028, Obligated Amount: $255716; Anticipated Amount: $255716
Host-directed Proteolysis-Targeting Chimera (PROTAC) approach to target intracellular Mycobacterium tuberculosis"., Global Alliance for TB Drug Development., 7/15/2024 - 7/14/2026, Obligated Amount: $97142.67; Anticipated Amount: $97142.67
In Vitro Testing Of Candidate Anti-Tubercular Compounds (Master under 109178), Global Alliance for TB Drug Development., 4/1/2023 - 3/31/2027, Obligated Amount: $2396127.36; Anticipated Amount: $2396127.36
To identify natural product molecules with potential activity against tuberculosis, National Institutes of Health (National Cancer Institute)., 1/6/2023 - 1/5/2025, No Obligated Amount Set; No Anticipated Amount Set
Design, Syntheses and Studies of Novel Antituberculosis Agents, University of Notre Dame., 9/1/2021 - 8/31/2026, Obligated Amount: $464304; Anticipated Amount: $464304
Provide heat inactivated cell suspensions of four mycobacterial strains to EpicGenetics, EpicGenetics., 8/1/2021 - 1/31/2022, Obligated Amount: $3980; Anticipated Amount: $3980
★ Modulation of Protein production and Degradation as an integrated approach to rapid sterilization of Drug sensitive and resistant Mtb, Global Alliance for TB Drug Development., 4/1/2019 - 3/31/2024, Obligated Amount: $8489541; Anticipated Amount: $8489541
★ In Vitro Testing of Candidate Anti-Tubercular Compounds (MASTER under 109178), Global Alliance for TB Drug Development., 10/1/2005 - 3/31/2024, Obligated Amount: $10312702; Anticipated Amount: $10312702
Selected Publications
Ragno, Rino, Zwergel, Clemens, Valente, Sergio, Astolfi, Roberta, Lambona, Chiara, Proia, Eleonora, Giuliani, Lidia, Franzblau, Scott G, Fioravanti, Rossella, Mai, Antonello. (2026). Combined computational and classical medicinal chemistry procedure to disclose novel pyrrole-based compounds as potential antituberculosis agents. Journal of Computer-Aided Molecular Design, 40, (1), 92. doi:10.1007/s10822-026-00794-6.
Thompson, Andrew M, Cheung, Chen-Yi, McNeil, Matthew B, Campbell, Ashley C, Záhorszká, Monika, Korduláková, Jana, Stelitano, Giovanni, Recchia, Deborah, Pasca, Maria Rosalia, Wan, Baojie, Khan, Shahebraj, Nikolic, Dejan S, Shetye, Gauri S, Franzblau, Scott G, Denny, William A, Cook, Gregory M, Krause, Kurt L. (2026). Advancing the antituberculosis activity of nitropicolinic acids and amides. European Journal of Medicinal Chemistry, 302, (Pt 2), 118324. doi:10.1016/j.ejmech.2025.118324.
Ratia, Kiira, Jin, Shengnan, Abad-Zapatero, Celerino, Shetye, Gauri S, Demissie, Robel, Qader, Mallique, Beautrait, Alexandre, Nikolic, Dejan S, Wolf, Nina M, Rubin, Eric J, Krandor, Olga, Serbina, Natalya, Li, Guiying, Pauli, Guido F, Klein, Larry L, Cho, Sanghyun, Franzblau, Scott G, Fotouhi, Nader, Kaneko, Takushi, Lee, Hyun. (2025). Unique Interactions of Novel Rufomycin “Click Chemistry” Analogs with Mtb ClpC1 and Implications. Journal of Medicinal Chemistry, 68, (24), 26298-26310. doi:10.1021/acs.jmedchem.5c02416.
Wang, Mingqian, He, YongLe, Cohen, Siobhan A, Strohm, Amanda R, Shetye, Gauri, Franzblau, Scott G, Walker, Stephen G, Alley, MRK, Tonge, Peter J. (2025). Selectivity of the Time-Dependent M. tuberculosis LeuRS Inhibitor Ganfeborole Is Driven by Target Vulnerability. ACS Chemical Biology, 20, (12), 2955-2965. doi:10.1021/acschembio.5c00705.
Lee, Jung-Ho, Tan, Jin Yi, Ma, Rui, Nguyen, Linh, Kahn, Shahebraj, Qader, Mallique, Mpofu, Enock, Shetye, Gauri, Krull, Nyssa K, Augustinović, Mario, Omarsdottir, Sesselja, Edmonson, William, Rodriguez, Jonathon, Cho, Sanghyun, Franzblau, Scott G, Murphy, Brian T. (2025). Antibiotic discovery from a bacterial colony: isolation of new peptidic antibiotics using robotics, 3D printed bioassays, and MS-based bioinformatics. Phytochemistry Letters, 69, 103160. doi:10.1016/j.phytol.2025.103160.
Kauffman, John, Cuevas, Jake, Feiner, Janaya, Metzger, Margaret, Shetye, Gauri, Wan, Baojie, Qader, Mallique, Nguyen, Duc, Nugent, Angela, Hossain, Akil, Franzblau, Scott, Umesiri, Francis E. (2025). Discovery of ultra short β-peptoids with selective activity against drug-resistant Mycobacterium tuberculosis. European Journal of Medicinal Chemistry, 290, 117531. doi:10.1016/j.ejmech.2025.117531.
Kumar, Boddupalli Venkata Siva, Talamadla, Mahesh Kumar, Nandikolla, Adinarayana, Khetmalis, Yogesh Mahadu, Shetye, Gauri, Franzblau, Scott G, Murugesan, Sankaranarayanan, Sekhar, Kondapalli Venkata Gowri Chandra. (2025). Exploration of quinoxaline triazoles as antimycobacterial agents: design, synthesis and biological evaluation. Bioorganic & Medicinal Chemistry Letters, 121, 130177. doi:10.1016/j.bmcl.2025.130177.
Su, Chun, Tuan, Nguyen-Quang, Li, Wen-Hua, Cheng, Jin-Hua, Jin, Ying-Yu, Hong, Soon-Kwang, Lee, Hyun, Qader, Mallique, Klein, Larry, Shetye, Gauri, Pauli, Guido F, Flanzblau, Scott G, Cho, Sang-Hyun, Zhao, Xin-Qing, Suh, Joo-Won. (2025). Enhancing rufomycin production by CRISPR/Cas9-based genome editing and promoter engineering in Streptomyces sp. MJM3502. Synthetic and Systems Biotechnology, 10, (2), 421-432. doi:10.1016/j.synbio.2025.01.002.
Zhou, Bin, Shetye, Gauri, Klein, Larry L, Wolf, Nina M, Lee, Hyun, McAlpine, James B, Harris, Guy, Chen, Shao-Nong, Suh, Joo Won, Cho, Sang-Hyun, Franzblau, Scott G, Abad-Zapatero, Celerino, Pauli, Guido F. (2025). Structure-Based Analysis of Semisynthetic Anti-TB Rufomycin Analogues. Journal of Natural Products, 88, (4), 907-925. doi:10.1021/acs.jnatprod.4c01266.
Notable Honors
2026, UIC Global Scholar, University of Illinois Chicago
2026, Member, Sigma Xi Research Honor Society, Sigma Xi Research Honor Society
2024, UIC Global Scholar, Neal McCrillis
2024, Fellow, American Academy of Microbiology, American Academy of Microbiology
2024, Fellow, American Academy of Microbiology, American Society for Microbiology
2024, Fellow, American Academy of Microbiology, American Society for Microbiology
Education
Degrees:
B.S, Rutgers University, United States, 1976
MS, University of Arizona, United States, 1978
PhD, University of Arizona, United States, 1982
Postgraduate Training:
Postgraduate, Kurume University, Japan, 1984
Professional Memberships
American Chemical Society, 4/15/2026 - Present
American Society for Microbiology, 4/15/2026 - Present
Selected Presentations
Moraski, Garret, Marshall, Kate, Schorey, Jeffrey, Choi, Kyung Bae, Cho, Sanghyun, Franzblau, Scott, Frey, Carrie, Joseph, Ivan, Claypool, William, Miller, Marvin. (2025 July 23). Next Generation Imidazo[1,2,-a]pyridine-3-carboxamides. Gordon Research Conference on Tuberculosis Drug Discovery and Development. Barcelona, Spain.