Selected scientific accomplishments from the SMSF are below. These include research from John Denu, Tim Bugni, David Andes, and Christian Capitini.
Discovery and Mechanism of Small Molecule Inhibitors Selective for the Chromatin-Binding Domains of Oncogenic UHRF1
John Denu, PhD – Genetic and Epigenetic Mechanisms (GEM)
NIH R01 GM059785
- Overexpressed UHRF1 has been observed in numerous cancers
- HTS of 100K compounds for inhibitors of UHRF1
- AlphaScreen in 1536 well plates
- Three lead compounds identified
Wallace H Liu, Robert E Miner 3rd, Brittany N Albaugh, Gene E Ananiev, Scott A Wildman, John M Denu. Biochemistry 2022 Mar 1;61(5):354-366. doi: 10.1021/acs.biochem.1c00698. Epub 2022 Feb 10
Biemamides A-E, Inhibitors of the TGF-β Pathway That Block the Epithelial to Mesenchymal Transition
Tim Bugni, PhD – Developmental Therapeutics Program (DT)
NIH R01 GM104192
- In established cancers, TGF-β is a central player in tumor growth, invasion, and subsequent metastasis.
- HTS of marine natural products for inhibitors of TGF-β.
- Five pyrimidinedione derivatives, biemamides A–E identified as inhibitors
- Biemamides blocked TGF-β-induced transition of the NMuMG epithelial cells into mesenchymal cells.
- Biemamides influence in vivo developmental processes related to body size regulation of Caenorhabditis elegans.
Zhang F, Braun DR, Ananiev GE, Hoffmann FM, Tsai IW, Rajski SR, Bugni TS. Org Lett. 2018 Sep 21;20(18):5529-5532. doi: 10.1021/acs.orglett.8b01871. Epub 2018 Aug 30.
A marine microbiome antifungal targets urgent-threat drug-resistant fungi
David Andes, MD and Tim Bugni, PhD – Infectious Diseases
U19 AI109673 and U19 AI142720
- A novel anti fungal agent Turbinmicin discovery from marine microbiome using MDR drug discovery platform.
- Turbinmicin displays potent in vitro and in vivo efficacy against multiple MDR fungal pathogens.
- MOA hypothesis is that turbinmicin impairs vesicle-mediated trafficking by inhibiting Sec14p.
Zhang F, Zhao M, Braun DR, Ericksen SS, Piotrowski JS, Nelson J, Peng J, Ananiev GE, Chanana S, Barns K, Fossen J, Sanchez H, Chevrette MG, Guzei IA, Zhao C, Guo L, Tang W, Currie CR, Rajski SR, Audhya A, Andes DR, Bugni TS. Science. 2020 Nov 20;370(6519):974-978. doi: 10.1126/science.abd6919.
Combining Immunocytokine and Ex Vivo Activated NK Cells as a Platform for Enhancing Graft-Versus-Tumor Effects Against GD2 + Murine Neuroblastoma
Christian Capitini, MD – Developmental Therapeutics Program (DT)
NCI/NIH R01 CA215461
- Management for high-risk neuroblastoma (NBL) has included autologous hematopoietic stem cell transplant (HSCT) and anti-GD2 immunotherapy, but survival remains around 50%.
- Allogeneic HSCT alone was insufficient to control NXS2 tumor growth, but the addition of hu14.18-IL2 controlled tumor growth and improved survival.
Bates PD, Rakhmilevich AL, Cho MM, Bouchlaka MN, Rao SL, Hales JM, Orentas RJ, Fry TJ, Gilles SD, Sondel PM, Capitini CM. Front Immunol. 2021 Aug 19;12:668307. doi: 10.3389/fimmu.2021.668307. eCollection 2021.
ACKNOWLEDGMENTS
Funding received from the UWCCC Cancer Center Support Grant (CCSG) for published research, including the use of UWCCC Shared Resources to generate or analyze data, or conduct clinical trials, needs to reference the UWCCC. See Acknowledging UWCCC in Publications, Posters, and Presentations. Please acknowledge “UWCCC Small Molecule Screening Facility” for any work supported by the SMSF. Thank you!
Sample Acknowledgment “The author(s) thank the University of Wisconsin Carbone Cancer Center Small Molecule Screening Facility, supported by P30 CA014520, for use of its facilities and services.”
View the UW Research Expertise website for more information on other UW–Madison laboratory facilities that provide state-of-the-art instrumentation and expert scientific staff.