Positions
- Professor
-
Biochemistry & Molecular Pharmacology
Baylor College of Medicine
- Professor
-
Molecular & Cellular Biology
Baylor College of Medicine
- Professor
-
Molecular Virology & Microbiology
Baylor College of Medicine
- Member
-
Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States
- Member
-
Center for Drug Discovery
Baylor College of Medicine
Houston, Texas United States
Addresses
- Department of Biochemistry (Office)
-
Baylor College of Medicine
Houston, TX 77030-3498
United States
Phone: (713) 798-8668
ftsai@bcm.edu
Education
- Advanced Training from Yale University / HHMI
- 10/2000 - New Haven, Connecticut United States
- D.Phil. from University of Oxford
- 10/1997 - Oxford, Oxon United Kingdom
- BSc from Univ. of London (Imperial College)
- 08/1993 - London, South Kensington United Kingdom
Honors & Awards
- Georgia Cancer Center Distinguished Guest Lecturer
- 01/2019
- Norman Hackerman Award in Chemical Research
- 02/2008
- Research Scholar of the American Cancer Society
- 01/2008 - 12/2011
- Scientist of the American Heart Association
- 01/2001 - 12/2004
- Wellcome Trust International Prize Travelling Postdoctoral Fellow
- 01/1997 - 12/1999
- NIH NRSA (F32) Individual Postdoctoral Fellowship (declined)
- 11/1996
- Associate of the Royal College of Science, United Kingdom
- 08/1993
Professional Interests
- Protein Structure-Function and Protein Folding
- Structural Biology and Macromolecular Assemblies
- Cryo-electron Microscopy and Tomography
- Membranes and Membrane Proteins
- Enzymology
- Gene Expression and Regulation
- Cancer
- Antibiotic Resistance
- Nano Medicine and Drug Design
- Bacteria and Phage
- Yeast and Dictyostelium
Professional Statement
Mitochondria degeneration and dysfunction are hallmarks of aging-related human diseases including cancer and neurodegenerative diseases such as Alzheimer's and related dementias. Our laboratory uses cutting-edge structural biology methods, as well as biochemistry, molecular, and chemical biology to understand how protein quality control machines maintain proteostasis under normal and pathological conditions, and to identify factors that selectively induce apoptosis, for instance, of cancer cells. A key objective is to dissect the molecular interactions between stress chaperones and energy-dependent proteases, and how protein machines harness metabolic energy to assist in protein folding as well as unfolding, and selectively degrade excess and damaged proteins. We are motivated to better understand mechanisms regulating proteostasis in cells originating from all domains of life, and to exploit our molecular understanding to restore proteostasis balance in disease states.We value diversity in all its forms, including race, ethnicity, gender, sexual orientation, ability, and nationality, and strive to cultivate a diverse and inclusive environment for research.
Websites
Selected Publications
- Ho A, Lee S, Tsai FTF "A foundation chemical language model for comprehensive fragment-based drug discovery." arXiv. 2025 Sep 23;2509.19586
- Lee S, Lee SB, Sung N, Xu WW, Chang C, Kim HE, Catic A, Tsai FTF "Structural basis of impaired disaggregase function in the oxidation-sensitive SKD3 mutant causing 3-methylglutaconic aciduria." Nature Commun. 2023;14:2028. Pubmed PMID: 37041140
- Lee G, Kim RS, Lee SB, Lee S, Tsai FTF "Deciphering the mechanism and function of Hsp100 unfoldases from protein structure." Biochem. Soc. Trans. 2022;50:1725-36. Pubmed PMID: 36454589
- Mercado JM, Lee S, Chang C, Sung N, Soong L, Catic A, Tsai FTF "Atomic structure of the Leishmania spp. Hsp100 N-domain." Proteins. 2022;90:1242-6. Pubmed PMID: 35122310
- Lee S, Roh SH, Lee J, Sung N, Liu J, Tsai FTF "Cryo-EM structures of the Hsp104 protein disaggregase captured in the ATP conformation." Cell Rep. 2019;26:29-36. Pubmed PMID: 30605683
- Sung N, Lee J, Kim JH, Chang C, Joachimiak A, Lee S, Tsai FT "Mitochondrial Hsp90 is a ligand-activated molecular chaperone coupling ATP binding to dimer closure through a coiled-coil intermediate." Proc. Natl. Acad. Sci. USA. 2016;113:2952-7. Pubmed PMID: 26929380
- Lee J, Kim JH, Biter AB, Sielaff B, Lee S, Tsai FT "Heat shock protein (Hsp) 70 is an activator of the Hsp104 motor." Proc. Natl. Acad. Sci. USA. 2013;110:8513-8. Pubmed PMID: 23650362
- Biter AB, Lee S, Sung N, Tsai FT "Structural basis for intersubunit signaling in a protein disaggregating machine." Proc. Natl. Acad. Sci. USA. 2012;109:12515-20. Pubmed PMID: 22802670
- Lee S, Augustin S, Tatsuta T, Gerdes F, Langer T, Tsai FT "Electron cryomicroscopy structure of a membrane-anchored mitochondrial AAA protease." J. Biol. Chem. 2011;286:4404-11. Pubmed PMID: 21147776
- Sielaff B, Lee KS, Tsai FT "Structural and functional conservation of Mycobacterium tuberculosis GroEL paralogs suggests that GroEL1 is a chaperonin." J. Mol. Biol. 2011;405:831-9. Pubmed PMID: 21094166
- Lee S, Sielaff B, Lee J, Tsai FT "CryoEM structure of Hsp104 and its mechanistic implication for protein disaggregation." Proc. Natl. Acad. Sci. USA. 2010;107:8135-40. Pubmed PMID: 20404203
- Lee S, Choi JM, Tsai FT "Visualizing the ATPase cycle in a protein disaggregating machine: structural basis for substrate binding by ClpB." Mol. Cell. 2007;25:261-71. Pubmed PMID: 17244533
- Weibezahn J, Tessarz P, Schlieker C, Zahn R, Maglica Z, Lee S, Zentgraf H, Weber-Ban EU, Dougan DA, Tsai FT, Mogk A, Bukau B "Thermotolerance requires refolding of aggregated proteins by substrate translocation through the central pore of ClpB." Cell. 2004;119:653-65. Pubmed PMID: 15550247
- Lee S, Sowa ME, Watanabe YH, Sigler PB, Chiu W, Yoshida M, Tsai FT "The structure of ClpB: a molecular chaperone that rescues proteins from an aggregated state." Cell. 2003;115:229-40. Pubmed PMID: 14567920
- Tsai FT, Sigler PB "Structural basis of preinitiation complex assembly on human pol II promoters." EMBO J. 2000;19:25-36. Pubmed PMID: 10619841
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