Thomas R. Cech, Ph.D.
Distinguished Professor

Office: JSCBB B421
Lab: JSCBB B455
Lab Phone: 303-492-8304
Fax: 303-492-6194


Ph.D.: University of California, Berkeley, 1975

Areas of Expertise

Nucleic Acids

Awards and Honors

  • 2000 National Academy of Medicine
  • 1995 National Medal of Science
  • 1992 European Molecular Biology Organization
  • 1989 Nobel Prize in Chemistry
  • 1988 Heineken Prize
  • 1988 Gairdner International Award
  • 1988 Lasker Award
  • 1988 American Academy of Arts and Sciences Member
  • 1987 U.S. Steel Award in Molecular Biology
  • 1987 National Academy of Sciences Member
  • 1986 American Cancer Society Lifetime Research Professor
  • 1985 Guggenheim Fellow
  • 1985 Pfizer Award in Enzyme Chemistry
  • 1980 USPHS Research Career Development Award

Mechanism of Functional RNPs: Telomerase and lncRNPs

After their discovery of self-splicing RNA and RNA catalysis (1982), the Cech Lab studied the mechanism of catalytic RNAs (ribozymes) at both the chemical and the biological levels.  This work integrated enzymology, biophysics, chemical synthesis, molecular biology and genetics, and culminated with the determination of crystal structures of a large ribozyme domain and of entire active ribozymes.  As a result of this and other work, we now have a reasonable understanding of how ribonucleotides can form active sites for biological catalysis.

Starting in 1997 with their discovery of TERT (Telomerase Reverse Transcriptase), the Cech Lab has increasingly turned its attention to the RNP (ribonucleoprotein) world.  They defined functions for different domains of the TERT protein and of the telomerase RNA subunit in budding yeast, fission yeast, and Tetrahymena, and they investigated the functions of additional regulatory subunits.  At the same time, their finding of the telomere end-binding protein POT1 (protection of telomeres 1) led to determination of the molecular structure of this protein bound to single-stranded telomeric DNA.  Recent research has addressed the question of how telomeric DNA-binding proteins recruit human telomerase in cells, using CRISPR genome editing and single-molecule live-cell imaging. At the same time, the lab has interrogated the mechanisms by which a promoter mutation in the TERT gene activates telomerase to promote cancer cell proliferation.

Vast numbers of lncRNAs (long non-coding RNAs) have been identified by genome-wide analysis in mammals, some of which are involved in regulating histone-modifying proteins and thereby transcription.  The Cech Lab is taking a mechanistic and biophysical approach to proteins that bind these lncRNAs, with current emphasis on PRC2 (polycomb repressive complex 2).  They are combining protein purification and rigorous binding analyses with genome-wide experiments and single-molecule live-cell imaging to interrogate the biology of these abundant RNPs.

  • Lim, C. J., Barbour, A. T., Zaug, A. J., Goodrich, K. J., McKay, A. E., Wuttke, D. S., & Cech, T. R. The structure of human CST reveals a decameric assembly bound to telomeric DNA. Science, 368, 1081-1085 (2020).
  • Youmans, D.T., Gooding, A.R., Dowell, R.D., Cech, T.R. Competition between PRC2.1 and 2.2 subcomplexes regulates PRC2 chromatin occupancy in human stem cells. Mol Cell, 81, 488-501 (2021).
  • Zaug, A. J., Lim, C.J., Olson, C.L., Carilli, M.T., Goodrich, K.J., Wuttke, D.S., Cech, T.R., CST does not evict elongating telomerase but prevents initiation by ssDNA binding. Nucleic Acids Res, 49, 11653-11665 (2021). 
  • Zaug, A. J., Goodrich, K. J., Song, J. J., Sullivan, A. E. & Cech, T. R. Reconstitution of a telomeric replicon organized by CST. Nature, 608, 819-825 (2022).
  • Jansson-Fritzberg, L. I., Sousa, C. I., Smallegan, M. J., Song, J. J., Gooding, A. R., Kasinath, V., Rinn, J. L., & Cech, T. R. DNMT1 inhibition by pUG-fold quadruplex RNA. RNA, 29, 346–360 (2023).
  • Hemphill, W. O., Voong, C. K., Fenske, R., Goodrich, J. A., & Cech, T. R.  Multiple RNA- and DNA-binding proteins exhibit direct transfer of polynucleotides with implications for target-site search. Proc Natl Acad Sci U S A, 120, e2220537120 (2023).