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RESEARCH FOCUS AREAS:
- Breast cancer
- Nuclear receptors
- Drug resistance
- Structure-based drug discovery
RESEARCH SUMMARY:
Nuclear Receptors (NRs) are small molecule-activated transcription factors and key drivers of cancer pathology. Because NR genomic activities are highly dependent on the binding of small molecules to reprogram transcription, they are ideal therapeutic targets for a diverse range of diseases. In fact, 16% of all FDA approved drugs target NRs. Our goal is to understand how small molecules influence NR structures, alter their genomic activities, and achieve breast cancer-specific therapeutic endpoints. These structures enable the rational design of improved therapeutic small molecules which will be used as anti-cancer agents to address the unmet therapeutic needs of breast cancer patients.
EDUCATION:
- BS in Biochemistry, Virginia Tech
- PhD in Chemistry and Biochemistry, Northern Illinois University
- Postdoctoral Fellow: University of Chicago
SELECT PUBLICATIONS:
- Unconventional isoquinoline-based SERMs elicit fulvestrant-like transcriptional programs in ER+ breast cancer cells Hancock, GR; Young, KS; Hosfield, DJ; Joiner, C; Sullivan, EA; Yildiz, Y; Lainé, M; Greene, GL Fanning, SW npj Breast Cancer 2022;8(1):130. doi: 10.1038/s41523-022-00497-9
- ESR1 activating mutations: From structure to clinical application Grinshpun, A; Chen, V; Sandusky, ZM; Fanning, SW; Jeselsohn, R Biochimica et Biophysica Acta – Reviews on Cancer 2022 Nov 4;1878(1):188830. doi: 10.1016/j.bbcan.2022.188830. Epub ahead of print. PMID: 36336145
- Targeting MYC with modular synthetic transcriptional repressors derived from bHLH DNA-binding domains Speltz, TE; Qiao, Z; Swenson, CS; Shangguan, X; Coukos, JS; Lee, CW; Thomas, DM; Santana, J; Fanning, SW; Greene, GL; Moellering, RE Nature Biotechnology 2022 Oct 27. doi: 10.1038/s41587-022-01504-x. Epub ahead of print. PMID: 36302987
- Labeling of a mutant estrogen receptor with an Affimer in a breast cancer cell line Ren, P; Tiede, C; Fanning, SW; Adams, T; Speirs, V; Nelson, ER; Cheng, C; Moore, TW; Greene, GL; Tomlinson, D; Selvin, PR Biophysical Journal 2022 Oct 4;121(19):3651-3662. doi: 10.1016/j.bpj.2022.06.028. Epub 2022 Jun 30. PMID: 35778844; PMCID: PMC9617163
- A new chemotype of chemically tractable Nnonsteroidal estrogens based on a Thieno[2;3-d]pyrimidine core Sammeta, VR; Norris, JD; Artham, S; Torrice, CD; Byemerwa, J; Joiner, C; Fanning, SW; McDonnell, DP; Willson, TM ACS Medicinal Chemistry Letters 2022 Jun 10;13(7):1151-1158. doi: 10.1021/acsmedchemlett.2c00180. PMID: 35859859; PMCID: PMC9290010
- Stereospecific lasofoxifene derivatives reveal the interplay between estrogen receptor alpha stability and antagonistic activity in ESR1 mutant breast cancer cells Hosfield, DJ; Weber, S; Li, NS; Sauvage, M; Joiner, CF; Hancock, GR; Sullivan, EA; Ndukwe, E; Han, R; Cush, S; Lainé, M; Mader, SC; Greene, GL; Fanning, SW Elife 2022 May 16;11:e72512. doi: 10.7554/eLife.72512. PMID: 35575456; PMCID: PMC9177151
- Defining the energetic basis for a conformational switch mediating ligand-independent activation of mutant estrogen receptors in breast cancer Mayne, CG; Toy, W; Carlson, KE; Bhatt, T; Fanning, SW; Greene, GL; Katzenellenbogen, BS; Chandarlapaty, S; Katzenellenbogen, JA; Tajkhorshid, E Molecular Cancer Research 2021 Sep;19(9):1559-1570. doi: 10.1158/1541-7786.MCR-20-1017. Epub 2021 May 21. PMID: 34021071; PMCID: PMC8419021
- A small-molecule activator of the unfolded protein response eradicates human breast tumors in mice Boudreau, MW; Duraki, D; Wang, L; Mao, C; Kim, JE; Henn, MA; Tang, B; Fanning, SW; Kiefer, J; Tarasow, TM; Bruckheimer, EM; Moreno, R; Mousses, S; Greene, GL; Roy, EJ; Park, BH; Fan, TM; Nelson, ER; Hergenrother, PJ; Shapiro, DJ Science Translational Medicine 2021 Jul 21;13(603):eabf1383. doi: 10.1126/scitranslmed.abf1383. PMID: 34290053; PMCID: PMC8456366
- Lasofoxifene as a potential treatment for therapy-resistant ER-positive metastatic breast cancer Lainé, M; Fanning, SW; Chang, YF; Green, B; Greene, ME; Komm, B; Kurleto, JD; Phung, L; Greene, GL Breast Cancer Research 2021 May 12;23(1):54. doi: 10.1186/s13058-021-01431-w. PMID: 33980285; PMCID: PMC8117302
- Rapid induction of the unfolded protein response and apoptosis by estrogen mimic TTC-352 for the treatment of endocrine-resistant breast cancer Abderrahman, B; Maximov, PY; Curpan, RF; Fanning, SW; Hanspal, JS; Fan, P; Foulds, CE; Chen, Y; Malovannaya, A; Jain, A; Xiong, R; Greene, GL; Tonetti, DA; Thatcher, GRJ; Jordan, VC Molecular Cancer Therapeutics 2021 Jan;20(1):11-25. doi: 10.1158/1535-7163.MCT-20-0563. Epub 2020 Nov 11. PMID: 33177154; PMCID: PMC7790886
FULL LISTING OF PUBLICATIONS
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