@article{2d4b2c4f890c419ab37b31727f5e570d,
title = "Simultaneous Control of Endogenous and User-Defined Genetic Pathways Using Unique ecDHFR Pharmacological Chaperones",
abstract = "Ramadurgum et al. identify 17 new stabilizers of the E. coli dihydrofolate reductase (ecDHFR) destabilizing domain (DD) and validate them both in vitro and in vivo (mouse ocular and hepatic tissue). They also demonstrate the ability of these compounds to simultaneously control endogenous (stabilizer-defined) and user-defined (ecDHFR-DD-based) pathways.",
keywords = "E. coli dihydrofolate reductase, chemical biology, conditional regulation, destabilizing domain, dual use, gene therapy, high-throughput screening, ocular, pharmacological chaperone",
author = "Prerana Ramadurgum and Woodard, {Da Nae R.} and Steffi Daniel and Hui Peng and Mallipeddi, {Prema L.} and Hanspeter Niederstrasser and Melina Mihelakis and Chau, {Viet Q.} and Douglas, {Peter M.} and Posner, {Bruce A.} and Hulleman, {John D.}",
note = "Funding Information: V.Q.C. was supported by funding from the UT Southwestern Summer Medical Student Research Program. J.D.H. is supported by an endowment from the Roger and Dorothy Hirl Research Fund , a vision research grant from the Karl Kirchgessner Foundation , a National Eye Institute (NEI) R21 grant ( EY028261 ), an NEI R01 grant ( EY027785 ), and a Career Development Award from RPB. Additional support was provided by an NEI Visual Science Core grant ( P30 EY030413 ) and an unrestricted grant from RPB (both to the UT Southwestern Department of Ophthalmology). This project was supported by an NIH Shared Instrumentation S10 grant for the InCell Analyzer 6000 ( ODO018005-01 to B.A.P.), and screening costs were subsidized by the Simmons National Cancer Institute -funded Cancer Center Support grant ( 5P30 CA 142543-03 ) and UT Southwestern . M.M. and P.M.D. are supported by the Welch Foundation ( I-1920-20170325 ), a National Institute on Aging (NIA) R01 grant ( AG061338 ), a CPRIT grant ( RR150089 ), and the Harmon Center for Regenerative Science and Medicine (UT Southwestern). Funding Information: V.Q.C. was supported by funding from the UT Southwestern Summer Medical Student Research Program. J.D.H. is supported by an endowment from the Roger and Dorothy Hirl Research Fund, a vision research grant from the Karl Kirchgessner Foundation, a National Eye Institute (NEI) R21 grant (EY028261), an NEI R01 grant (EY027785), and a Career Development Award from RPB. Additional support was provided by an NEI Visual Science Core grant (P30 EY030413) and an unrestricted grant from RPB (both to the UT Southwestern Department of Ophthalmology). This project was supported by an NIH Shared Instrumentation S10 grant for the InCell Analyzer 6000 (ODO018005-01 to B.A.P.), and screening costs were subsidized by the Simmons National Cancer Institute-funded Cancer Center Support grant (5P30 CA 142543-03) and UT Southwestern. M.M. and P.M.D. are supported by the Welch Foundation (I-1920-20170325), a National Institute on Aging (NIA) R01 grant (AG061338), a CPRIT grant (RR150089), and the Harmon Center for Regenerative Science and Medicine (UT Southwestern). We thank Khiem T. Vu, MD for initial generation of the ARPE-19 R12Y/G67S/Y100I ecDHFR.YFP cell line. We thank Erdal Toprak, PhD (UT Southwestern) for access to the Tecan robot, Matthew E.R. Butchbach, PhD (University of Delaware) for providing RG3039 and D156844 for testing, and Matthew D. Shoulders, PhD (Massachusetts Institute of Technology) for providing the pLenti CMV puro dn.c-HSF1 plasmid. Conceptualization, J.D.H.; Investigation, P.R. D.R.W. S.D. H.P. P.L.M. H.N. M.M. V.Q.C. and J.D.H.; Writing ? Original Draft, P.R. and J.D.H.; Writing ? Review & Editing, P.R. D.R.W. S.D. H.P. P.L.M. H.N. M.M. V.Q.C. P.M.D. B.A.P. and J.D.H.; Funding Acquisition, P.M.D. B.A.P. and J.D.H.; Supervision, P.M.D. B.A.P. and J.D.H. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",
year = "2020",
month = may,
day = "21",
doi = "10.1016/j.chembiol.2020.03.006",
language = "English (US)",
volume = "27",
pages = "622--634.e6",
journal = "Cell Chemical Biology",
issn = "2451-9456",
publisher = "Elsevier Inc.",
number = "5",
}