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Interface of Evolution and Structure Based Drug Design



Our Lab

Constraining evolution and avoiding drug resistance

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Drug resistance occurs when, through evolution, a disease no longer responds to medications. Resistance impacts the lives of millions, limiting the effectiveness of many of our most potent drugs. This often happens under the selective pressure of therapy in bacterial, viral and fungal infections and cancer due to their rapid evolution.

We combine a variety of experimental and computational techniques to understand the molecular basis of drug resistance. Our new paradigm of drug design minimizes chances of resistance. Realizing that disrupting the drug target’s activity is necessary but not sufficient for developing a robust drug that avoids resistance.

Meet the Lab

Research Focus

Strategies and Systems

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We use multidisciplinary approaches, combining crystallography, enzymology, molecular dynamics and organic chemistry, to elucidate the molecular mechanisms of drug resistance. Resistance occurs when a heterogeneous populations of a drug target is challenged by the selective pressure of a drug. In cancer and viruses this heterogeneity is partially caused APOBEC3’s. We discovered resistance mutations occur either where drugs physically contact regions of the drug target that are not essential for substrate recognition or alter the ensemble dynamics of the drug target favoring substrate. We leverage these insights into a new strategies in structure-based drug design to minimize the likelihood for resistance by designing inhibitors to stay within the substrate envelope. This strategy not only describes most of the primary drug resistance for HIV, Hepatitis C viral protease inhibitors and influenza neuraminidase, but is generally applicable in the development of novel drugs that are less susceptible to resistance.

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In The News  

Read the latest news from the Schiffer Lab

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NEW Celia Schiffer, PhD, quoted in Science

 

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Publications

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Total: 1 results
  • Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors

    Thursday, November 09, 2023
    Author(s): Melissa L Boby,Daren Fearon,Matteo Ferla,Mihajlo Filep,Lizbé Koekemoer,Matthew C Robinson,COVID Moonshot Consortium‡,John D Chodera,Alpha A Lee,Nir London,Annette von Delft,Frank von Delft,Hagit Achdout,Anthony Aimon,Dominic S Alonzi,Robert Arbon,Jasmin C Aschenbrenner,Blake H Balcomb,Elad Bar-David,Haim Barr,Amir Ben-Shmuel,James Bennett,Vitaliy A Bilenko,Bruce Borden,Pascale Boulet,Gregory R Bowman,Lennart Brewitz,Juliane Brun,Sarma Bvnbs,Mark Calmiano,Anna Carbery,Daniel W Carney,Emma Cattermole,Edcon Chang,Eugene Chernyshenko,Austin Clyde,Joseph E Coffland,Galit Cohen,Jason C Cole,Alessandro Contini,Lisa Cox,Tristan Ian Croll,Milan Cvitkovic,Steven De Jonghe,Alex Dias,Kim Donckers,David L Dotson,Alice Douangamath,Shirly Duberstein,Tim Dudgeon,Louise E Dunnett,Peter Eastman,Noam Erez,Charles J Eyermann,Michael Fairhead,Gwen Fate,Oleg Fedorov,Rafaela S Fernandes,Lori Ferrins,Richard Foster,Holly Foster,Laurent Fraisse,Ronen Gabizon,Adolfo García-Sastre,Victor O Gawriljuk,Paul Gehrtz,Carina Gileadi,Charline Giroud,William G Glass,Robert C Glen,Itai Glinert,Andre S Godoy,Marian Gorichko,Tyler Gorrie-Stone,Ed J Griffen,Amna Haneef,Storm Hassell Hart,Jag Heer,Michael Henry,Michelle Hill,Sam Horrell,Qiu Yu Judy Huang,Victor D Huliak,Matthew F D Hurley,Tomer Israely,Andrew Jajack,Jitske Jansen,Eric Jnoff,Dirk Jochmans,Tobias John,Benjamin Kaminow,Lulu Kang,Anastassia L Kantsadi,Peter W Kenny,J L Kiappes,Serhii O Kinakh,Boris Kovar,Tobias Krojer,Van Ngoc Thuy La,Sophie Laghnimi-Hahn,Bruce A Lefker,Haim Levy,Ryan M Lithgo,Ivan G Logvinenko,Petra Lukacik,Hannah Bruce Macdonald,Elizabeth M MacLean,Laetitia L Makower,Tika R Malla,Peter G Marples,Tatiana Matviiuk,Willam McCorkindale,Briana L McGovern,Sharon Melamed,Kostiantyn P Melnykov,Oleg Michurin,Pascal Miesen,Halina Mikolajek,Bruce F Milne,David Minh,Aaron Morris,Garrett M Morris,Melody Jane Morwitzer,Demetri Moustakas,Charles E Mowbray,Aline M Nakamura,Jose Brandao Neto,Johan Neyts,Luong Nguyen,Gabriela D Noske,Vladas Oleinikovas,Glaucius Oliva,Gijs J Overheul,C David Owen,Ruby Pai,Jin Pan,Nir Paran,Alexander Matthew Payne,Benjamin Perry,Maneesh Pingle,Jakir Pinjari,Boaz Politi,Ailsa Powell,Vladimír Pšenák,Iván Pulido,Reut Puni,Victor L Rangel,Rambabu N Reddi,Paul Rees,St Patrick Reid,Lauren Reid,Efrat Resnick,Emily Grace Ripka,Ralph P Robinson,Jaime Rodriguez-Guerra,Romel Rosales,Dominic A Rufa,Kadi Saar,Kumar Singh Saikatendu,Eidarus Salah,David Schaller,Jenke Scheen,Celia A Schiffer,Christopher J Schofield,Mikhail Shafeev,Aarif Shaikh,Ala M Shaqra,Jiye Shi,Khriesto Shurrush,Sukrit Singh,Assa Sittner,Peter Sjö,Rachael Skyner,Adam Smalley,Bart Smeets,Mihaela D Smilova,Leonardo J Solmesky,John Spencer,Claire Strain-Damerell,Vishwanath Swamy,Hadas Tamir,Jenny C Taylor,Rachael E Tennant,Warren Thompson,Andrew Thompson,Susana Tomásio,Charles W E Tomlinson,Igor S Tsurupa,Anthony Tumber,Ioannis Vakonakis,Ronald P van Rij,Laura Vangeel,Finny S Varghese,Mariana Vaschetto,Einat B Vitner,Vincent Voelz,Andrea Volkamer,Martin A Walsh,Walter Ward,Charlie Weatherall,Shay Weiss,Kris M White,Conor Francis Wild,Karolina D Witt,Matthew Wittmann,Nathan Wright,Yfat Yahalom-Ronen,Nese Kurt Yilmaz,Daniel Zaidmann,Ivy Zhang,Hadeer Zidane,Nicole Zitzmann,Sarah N Zvornicanin
    Source: Science (New York, N.Y.)
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Contact Us

Office:
Lazare Research Building 928
Campus Map (pdf)

Email:
Celia.Schiffer@umassmed.edu

Mailing Address:
UMass Chan Medical School
Attn: Dr. Celia Schiffer/BMB Department
364 Plantation St LRB 928
Worcester, MA 01605

Join Us

We are always interested in applications from qualified candidates at postdoctoral and research associate levels.

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Undergraduates interested in pursuing a PhD at UMass Chan Medical School should apply directly to the Morningside Graduate School of Biomedical Sciences Program.