Samuel Sternberg, PhD

Profile Headshot

Overview

Academic Appointments

  • Assistant Professor of Biochemistry and Molecular Biophysics

Sam was born and raised in Lancaster, PA. He earned his B.A. in biochemistry from Columbia University in 2007, where he trained with Professor Ruben Gonzalez, and his Ph.D. in chemistry from the University of California, Berkeley in 2014, under the mentorship of Professor Jennifer Doudna. He was awarded graduate student fellowships from the National Science Foundation and the Department of Defense, and received the Scaringe Award from the RNA Society and the Harold Weintraub Graduate Student Award from the Fred Hutchinson Cancer Research Center. After a brief postdoc and book writing stint, Sam spent a year working at Caribou Biosciences, a Bay Area biotech start-up focusing on genome engineering applications, as a Scientist and Group Leader of Technology Development. He started his independent career in the Department of Biochemistry and Molecular Biophysics at Columbia in February, 2018.

Sam's doctoral and postdoctoral research focused on the mechanism of nucleic acid targeting by RNA-guided bacterial immune systems (CRISPR–Cas) and on the development of these systems for genome engineering applications. His work has been published in the journals Nature, Science, and Cell, and been covered in The New York Times, Science News, The Scientist, and various other news outlets. His lab employs a range of biochemical, biophysical, and structural techniques to investigate CRISPR–Cas biology, with an eye towards applying mechanistic knowledge for tool development.

Sam is committed to being a supportive mentor and effective lab manager, and to nurturing a collaborative research environment. He has closely mentored over a dozen undergraduate and graduate students, and has participated in numerous mentorship programs, including Student Mentoring and Research Teams (SMART) and Howard Hughes Medical Institute’s Exceptional Research Opportunities Program (EXROP) at Berkeley. The desire to work with students in the lab was a major driver of Sam’s decision to transition from industry back to academia. Outside of the lab, Sam is a passionate advocate for science communication and science outreach. He regularly presents to public audiences on the discovery of CRISPR–Cas immune systems and the ensuing gene-editing revolution, including a TEDMED talk in 2015, and has co-authored a pop-sci book with Jennifer Doudna on the same topic, titled A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution.

Languages

  • German

Credentials & Experience

Education & Training

  • BA, 2007 Biochemistry, Columbia University
  • PhD, 2014 Chemistry, University of California, Berkeley

Honors & Awards

Scaringe Young Scientist Award, RNA Society; 2015

Harold M. Weintraub Graduate Student Award; 2015

Biophysical Society Education Travel Award; 2013

National Defense Science & Engineering Graduate Research Fellowship; 2011 – 2013

NSF Graduate Research Fellowship; 2009 – 2014

Graduated summa cum laude and with Departmental Honors, Dept. of Chemistry, Columbia University; 2007

Outstanding Undergraduate Research Award, Dept. of Chemistry, Columbia University; 2007

Phi Betta Kappa, Columbia University; 2007

NSF Leadership Travel Award; 2007

National Science Foundation (NSF) Research Experience for Undergraduates Program, Columbia University (Best student presentation); 2006

Irving Langmuir Scholars Program, Columbia University; 2006 – 2007

Dean’s List, Columbia University; 2003 – 2007

Thomas M. Macioce Scholarship, Columbia University; 2003 – 2006

Research

Exploring and exploiting CRISPR–Cas immune systems

At a cellular level, organisms face two fundamental challenges: maintaining integrity of the genome in response to mobile genetic elements and mutagens, and expressing a specific repertoire of genes at the correct time and proper level. It is now widely recognized that noncoding RNAs play crucial and surprisingly diverse roles in controlling both the expression of DNA, via transcriptional and posttranscriptional gene regulation, and the content of DNA itself, by mediating sequence-specific DNA cleavage events. The recent discovery of pervasive genome defense systems in bacteria and archaea known as CRISPR–Cas (Clustered Regularly Interspaced Short Palindromic Repeats–CRISPR-associated), and the development of these systems for genome engineering, highlight the biological power and technological potential of RNA-guided DNA control.

The Sternberg Lab broadly strives to expand our understanding of the ways in which noncoding RNAs conspire with effector proteins to target DNA. Focusing on evolutionarily distinct but analogous systems in both prokaryotes and eukaryotes, and  using a combination of biochemical, structural, and biophysical approaches, we are uncovering new biological function while simultaneously advancing novel tools with which to precisely manipulate the genome.

Selected Publications

Klompe, S.E., Sternberg, S.H. “Harnessing ‘a billion years of experimentation’: the ongoing exploration and exploitation of CRISPR–Cas immune systems.” CRISPR J, 2 (2018): 141–158.

Chen, J.S., Dagdas, Y.S., Kleinstiver, B.P., Welch, M.M., Sousa, A.A., Harrington, L.B., Sternberg, S.H., Joung, J.K., Yildiz, A., Doudna, J.A. “Enhanced proofreading governs CRISPR-Cas9 targeting accuracy.” Nature 550 (2017): 407–410.

Dagdas, Y.*, Chen, J.S.*, Sternberg, S.H., Doudna, J.A., Yildiz, A. “A conformational checkpoint between DNA binding and cleavage by CRISPR–Cas9.” Science Advances 3 (2017): eaao0027.

Jackson, R.N., van Erp, P.B., Sternberg, S.H., Wiedenheft, B. “Conformational regulation of CRISPR-associated nucleases.” Curr Opin Microbiol 21 (2017): 110-119.

Boyle, E.A.*, Andreasson, J.O.L.*, Chircus, L.M.*, Sternberg, S.H., Wu, M.J., Guegler, C.K., Doudna, J.A., Greenleaf, W.J. “High-throughput biochemical profiling reveals sequence determinants of dCas9 off-target binding and unbinding.” PNAS 114 (2017): 5461-5466.

Singh, D., Sternberg, S.H., Fei, J., Doudna, J.A., Ha, T. “Real-time observation of DNA recognition and rejection by the RNA-guided endonuclease Cas9.” Nat Comm 7 (2016): 1–8.

Sternberg, S.H.*, Richter, H.*, Charpentier, E., Qimron, U. “Adaptation in CRISPR-Cas systems.” Mol Cell 61 (2016): 797–808.

Sternberg, S.H., LaFrance, B., Kaplan, M., Doudna, J.A. “Conformational control of DNA target cleavage by CRISPR-Cas9.” Nature 527 (2015): 110–113.

Redding, S., Sternberg, S.H., Marshall, M., Gibb, B., Bhat, P., Guegler, C.K., Wiedenheft, B., Doudna, J.A., Greene, E.C. “Surveillance and processing of foreign DNA by the Escherichia coli CRISPR-Cas system.” Cell 163 (2015): 854–865.

Sternberg, S.H., Doudna, J.A. “Expanding the biologist’s toolkit with CRISPR-Cas9.” Mol Cell 58 (2015): 568–574.

Baltimore, D., Berg, P., Botchan, M., Carroll, D., Charo, R.A., Church, G., Corn, J.E., Daley, G.Q., Doudna, J.A., Fenner, M., Greely, H.T., Martin, G.S., Penhoet, E., Puck, J., Sternberg, S.H., Weissman, J.S., Yamamoto, K.R. “A prudent path forward for genomic engineering and germline gene modification.” Science 348 (2015): 36–38.

Wright, A.V.*, Sternberg, S.H.*, Taylor, D.W., Staahl, B.T., Bardales, J.A., Kornfeld, J.E., Doudna, J.A. “Rational design of a split-Cas9 enzyme complex.” PNAS 112 (2015): 2984–2989.

O’Connell, M.R., Oakes, B.L., Sternberg, S.H., East-Seletsky, A., Kaplan, M., Doudna, J.A. “Programmable RNA recognition and cleavage by CRISPR/Cas9.” Nature 516 (2014): 263–266.

Hochstrasser, M.L.*, Taylor, D.W.*, Bhat, P., Guegler, C.K., Sternberg, S.H., Nogales, E., Doudna, J.A. “CasA mediates Cas3-catalyzed target degradation during CRISPR RNA-guided interference.” PNAS 111 (2014): 6618–6623.

Jinek, M.*, Jiang, F.*, Taylor, D.W*., Sternberg, S.H.*, Kaya, E., Ma, E., Anders, C., Hauer, M., Zhou, K., Lin, S., Kaplan, M., Iavarone, A.T., Charpentier, E., Nogales, E., Doudna, J.A. “Structures of Cas9 endonucleases reveal RNA-mediated conformational activation.” Science 343 (2014): 1247997-1–11.

Sternberg, S.H.*, Redding, S.*, Jinek, M., Greene, E.C., Doudna, J.A. “DNA interrogation by the CRISPR RNA-guided endonuclease Cas9.” Nature 507 (2014): 62–67.

Haurwitz, R.E., Sternberg, S.H., Doudna, J.A. “Csy4 relies on an unusual catalytic dyad to position and cleave CRISPR RNA.” EMBO J 31 (2012): 2824–2832.

Sternberg, S.H., Haurwitz, R.E., Doudna, J.A. “Mechanism of substrate selection by a highly specific CRISPR endoribonuclease.” RNA 18 (2012): 661–672.

Wiedenheft, B., Sternberg, S.H., Doudna, J.A. “RNA-guided genetic silencing systems in bacteria and archaea.” Nature 482 (2012): 331–338.

Chakravarthy, S., Sternberg, S.H., Kellenberger, C.A., Doudna, J.A. “Substrate-specific kinetics of Dicer-catalyzed RNA processing.” J Mol Biol 404 (2010): 392–402.

Fei, J., Wang, J., Sternberg, S.H., MacDougall, D.D., Elvekrog, M.M., Pulukkunat, D.K., Englander, M.T., Gonzalez, R.L. “A highly purified, fluorescently labeled in vitro translation system for single-molecule studies of protein synthesis.” Meth Enzymol 472 (2010): 221–259.

Sternberg, S.H., Fei, J., Prywes, N., McGrath, K.A., Gonzalez, R.L. “Translation factors direct intrinsic ribosome dynamics during translation termination and ribosome recycling.” Nat Struct Mol Biol 16 (2009): 861–868.