Our laboratory aims to fundamentally change the paradigms of chemical biology and medicinal chemistry, with an ultimate goal to improve human health.

The COVID pandemic demonstrated how infectious diseases collectively represent tremendous and unpredictable challenges for humankind and how novel antivirals are urgently needed to continually improve and replenish our arsenal of therapeutics. The rate at which lead molecules derived from high-throughput screens are optimized for eventual human use (e.g. bench-to-bedside) is significantly hampered, as the modern drug discovery process is entirely reliant on the manual iteration of small molecule syntheses with biological assays. This dependence on skilled medicinal chemists makes medicinal chemistry incredibly time consuming and costly.

Our research program focusses on the development and expansion of each component of the structure-activity relationship paradigm with an emphasis on targeting host-microbe interactions both infectious microbes and commensal microbiome, and more recently cancer, with an ultimate goal to fundamentally change the medicinal chemistry and chemical biology, and eventually to improve human health.

1. Development of fundamental methodologies in medicinal chemistry    Our laboratory aims to develop and apply generally applicable methodologies in medicinal chemistry that accelerate the drug development using the state-of-art click chemistry and other technologies.
2. Chemical biology of host-microbe interactions      We aim to advance our understanding of host-microbe interactions, in particular microbiome, with cutting-edge chemical biology technologies, including chemical probes, HT assays, and chemical proteomics to characterize the biological roles of target proteins in the host-microbe interactions.
3. Expanding the modalities and function of small molecules               Traditionally, inhibition of biological pathways was the major biological functions of small molecules while recently other functions of small molecules are explored such as degradation or activation of target proteins. We aim to explore new modalities and functions of small molecules. These efforts enable us to modulate biological targets that are currently considered undruggable.

Kitamura S^#(Co-corresponding author), Lin, T-H, Lee C-CD, Takamura A, Kadam RU, Zhang D, Zhu X, Dada L, Nagai E, Yu W, Yao Y, Sharpless KB, Wilson IA^#, Wolan D.W^#. Ultra-potent influenza hemagglutinin fusion inhibitor developed through SuFEx-enabled high-throughput medicinal chemistry. Proc Natl Acad Sci USA. 2024;121(22):e2310677121. doi:10.1073/pnas.2310677121

Carter TR, Milosevich N, Dada L, Shaum JB, Sharpless KB, Kitamura S^# (co-corresponding author), Erb MA^#. SuFEx-based chemical diversification for the systematic discovery of CRBN molecular glues. Bioorg Med Chem. 2024:117699. doi:10.1016/j.bmc.2024.117699

Wang, Y.; Morisseau C.; Takamura, A.; Wan, D.; Li D.; Sidoli S.; Yang J.; Wolan, D.W.^#; Hammock, B.D. ^#; Kitamura, S.^# (corresponding). A PROTAC that induces lysosomal degradation of the cytosolic target protein. ACS Chemical Biology  2023. doi: 10.1021/acschembio.3c00017

Garnar-Wortzel, L.*, Bishop, T.*, Kitamura, S.* (co-first author); Milosevich, N.; Asiaban, J.;  Zhang, X.; Zheng, Q.; Chen, E.; Ramos, A.; Ackerman, C.; Hampton, E.; Chatterjee, A.; Young, T.; Hull, M.; Sharpless K.B.; Cravatt, B.; Wolan, D. W. ; Erb, M., Chemical inhibition of ENL/AF9 YEATS domains in acute leukemia. ACS Central Science 2021. doi: 10.1021/acscentsci.0c01550

Woehl, J.L.*; Kitamura, S.* (co-first author); Dillon, N.; Han, Z.; Edgar, L.J.; Nizet, V.; Wolan, D.W. An irreversible inhibitor to probe the role of Streptococcus pyogenes cysteine protease SpeB in evasion of host complement defenses. ACS Chemical Biology 2020, doi: 10.1021/acschembio.0c00191.

Kitamura, S.; Zheng, Q.; Woehl, J. L.; Solania, A.; Chen, E.; Dillon, N.; Hull M.; Kotaniguchi, M.; Kitamura, S.; Nizet, V.; Sharpless, K. B.; Wolan, D.W., (2020): SuFEx-Enabled High-Throughput Medicinal Chemistry. Journal of the American Chemical Society 2020, doi: 10.1021/jacs.9b13652.

Yao Y.; Kadam R.U.; Lee C.-C.D.; Woehl J.L.; Wu N.C.; Zhu X.; Kitamura S.; Wilson I.A.; Wolan D.W., An influenza A hemagglutinin small-molecule fusion inhibitor identified by a new high-throughput fluorescence polarization screen. Proceedings of the National Academy of  Sciences 2020, doi.org/10.1073/pnas.200689311.

Kok, B. P.; Ghimire, S.; Kim, W.; Chatterjee, S.; Johns, T.; Kitamura, S.; Eberhardt, J.; Ogasawara, D.;  Xu, J.; Sukiasyan, A.; Kim, S. M.; Godio, C.; Bittencourt, J. M.; Cameron, M.; Galmozzi, A.; Forli, S.; Wolan, D. W.; Cravatt, B. ; Boger, D. L.; Saez, E., Discovery of small-molecule enzyme activators by activity-based protein profiling. Nature Chemical Biology 2020, doi: 10.1038/s41589-020-0555-4.

Bess, E. N.;  Bisanz, J. E.;  Yarza, F.;  Bustion, A.;  Rich, B. E.;  Li, X.;  Kitamura, S.;  Waligurski, E.;  Ang, Q. Y.;  Alba, D. L.;  Spanogiannopoulos, P.;  Nayfach, S.;  Koliwad, S. K.;  Wolan, D. W.;  Franke, A. A.; Turnbaugh, P. J., Genetic basis for the cooperative bioactivation of plant lignans by Eggerthella lenta and other human gut bacteria. Nature Microbiology 2020, doi.org/10.1038/s41564-019-0596-1.

Kitamura, S.; Owensby, A.; Wall, D.; Wolan, D. W.; Lipoprotein signal peptidase inhibitors with antibiotic properties identified through design of a robust in vitro HT platform. Cell Chemical Biology 2017, doi: 10.1016/j.chembiol.2017.12.011.

Kitamura, S.; Hvorecny, KL.; Niu, J.; Hammock, BD.; Madden, DR.; Morisseau, C.; Rational design of potent and selective inhibitors of an epoxide hydrolase virulence factor from Pseudomonas aeruginosa. Journal of Medicinal Chemistry 2016, doi.org/10.1021/acs.jmedchem.6b00173.