Research
Thanks to the Human Microbiome Project, we know what bacteria are living at various locations on and inside a healthy human body. This research led to the surprising discovery that there are far more different kinds of bacteria present and at much higher numbers than was previously thought. Most of these bacteria are harmless, “good” organisms with the largest number living in the intestinal tract. They are essential to human health and life as they contribute to digesting food, providing essential nutrients and vitamins, and ensuring the effective operation of the immune system to prevent infection by disease-causing, “bad” bacteria. In fact, many recent studies have linked diseases of the digestive tract and skin to an imbalance in the bacterial community. It is therefore of great importance to understand how the right balance of microbes and their function is maintained in a healthy intestinal tract.
Where the Human Microbiome Project answered the initial question of “Who is there?”, we at the Claesen group focus on tackling the logical follow-up question “What are they doing?”. We discovered different classes of small molecules produced by “good”, commensal microbes that are used for communicating with other bacteria as well as with the host immune system. We predict that these are used in lively, molecular conversations that are essential for staying healthy. Our research will yield a better understanding of the role the microbiome plays in disease, as well as drive the development of microbiota-based therapies.
Biography
Jan was born and raised in Alken, a small town with a big brewery in Belgium. He obtained a B.S. and M.S. in Biological Engineering at the KU Leuven, Belgium, and specialized in Cell and Gene Biotechnology. Next, Jan joined the lab of Prof. Mervyn Bibb and he received his Ph.D. in Molecular Microbiology in 2011 from the John Innes Centre and University of East Anglia, Norwich, UK. His Ph.D. studies involved the genetics and biosynthesis of ribosomally synthesized and post-translationally modified peptide antibiotics in Streptomyces. After his graduate studies, Jan was a postdoctoral scholar in the lab of Dr. Michael Fischbach in the Department of Bioengineering and Therapeutic Sciences at the University of California, San Francisco, USA. There, his work focused on the characterization of bacterial metabolites that mediate microbe-microbe and microbe-host interactions in human gut and skin. The Claesen group was established at the Lerner Research Institute, Cleveland Clinic in November 2017. Our aim is to characterize the role of bioactive microbial and dietary small molecules in microbiota-associated diseases.
In his free time, Jan enjoys hiking, outdoors activities, cooking, traveling, RPG computer games, heavy and alternative music, Lego, and spending time with his wife and two daughters.
Education & Professional Highlights
Research
The Claesen group aims to functionally characterize molecular mechanisms that control bacterial interspecies and microbe-host interactions in the human microbiome. Bacteria use small molecule chemicals to mediate these interactions and the genetic information required for their production is typically encoded in one physical location of the bacterial chromosome, in biosynthetic gene clusters (BGCs). Using in silico techniques, we identified several widespread families of BGCs that we are now characterizing experimentally, prioritizing on the BGCs predicted to be involved in modulation of community composition or interaction with the host immune system. Our research will contribute to a better mechanistic understanding of the microbes that live in our gut and on our skin, leading to the discovery of druggable small molecules, new targets for antibacterial therapy and beneficial bacterial strains that can be employed for intervention therapies. The areas of expertise in the Claesen group include microbiology, bacterial genetics and synthetic biology, small molecule biosynthesis and biochemistry.
Our Team
Selected Publications
View publications for Jan Claesen, PhD
(Disclaimer: This search is powered by PubMed, a service of the U.S. National Library of Medicine. PubMed is a third-party website with no affiliation with Cleveland Clinic.)
22. Osborn LJ, K Schultz*, W Massey*, B DeLucia, I Choucair, V Varadharajan, K Fung, AJ Horak, D Orabi, I Nemet, LE Nagy, Z Wang, DS Allende, N Sangwan, AM Hajjar, C McDonald, PP Ahern, SL Hazen, JM Brown#, and J Claesen#. A gut microbial metabolite of dietary polyphenols reverses obesity-driven hepatic steatosis. bioRxiv, doi.org/10.1101/2021.09.16.460661 (preprint) (*equal contribution) (#co-corresponding)
21. Ozcam M, JH Oh, R Tocmo, D Acharya, S Zhang, S Ruiz-Ramírez, F Li, CC Cheng, E Vivas, FE Rey, J Claesen, T Bugni, J Walter, and JP van Pijkeren. A secondary metabolite drives intraspecies antagonism in a gut symbiont that is inhibited by peptidoglycan acetylation. bioRxiv, doi.org/10.1101/2021.06.11.448121 (preprint)
20. Chambers LM, EL Esakov, C Braley, L Trestan, Z Alali, D Bayik, JD Lathia, N Sangwan, P Bazeley, AS Joehlin-Price, M Dwidar, A Hajjar, PP Ahern, J Claesen, P Rose, R Vargas, JM Brown, C Michener, and O Reizes. Disruption of the gut microbiota attenuates epithelial ovarian cancer sensitivity to cisplatin therapy. bioRxiv, doi.org/10.1101/2020.06.16.155226 (preprint)
19. DeLucia B*, S Samorezov*, MT Zangara, RL Markley, LJ Osborn, KB Schultz, C McDonald, and J Claesen (2022). A 3D printable device allowing fast and reproducible longitudinal preparation of mouse intestines. Anim Models Exp Med, doi.org/10.1002/ame2.12228 (*equal contribution)
18. Osborn LJ, J Claesen#, and JM Brown# (2021). Microbial Flavonoid Metabolism: A Cardiometabolic Disease Perspective. Annu Rev Nutr, 41:433-454 (#co-corresponding)
17. Osborn LJ*, D Orabi*, M Goudzari, N Sangwan, R Banerjee, AL Brown, A Kadam, AD Gromovsky, P Linga, GAM Cresci, TD Mak, BB Willard, J Claesen#, and JM Brown# (2021). A Single Human-Relevant Fast Food Meal Rapidly Reorganizes Metabolomic and Transcriptomic Signatures in a Gut Microbiota-Dependent Manner. Immunometabolism, 3(4):e210029. (*equal contribution) (#co-corresponding)
16. Johnston I, LJ Osborn*, RL Markley*, EA McManus, A Kadam, KB Schultz, N Nagajothi, PP Ahern, JM Brown, and J Claesen (2021). Identification of essential genes for Escherichia coli aryl polyene biosynthesis and function in biofilm formation. NPJ Biofilms Microbiomes, 7: 56. (*equal contribution)
15. Orabi D*, LJ Osborn*, K Fung, W Massey, AJ Horak III, F Aucejo, I Choucair, B DeLucia, Z Wang, J Claesen, and JM Brown (2021). A surgical method for continuous intraportal infusion of gut microbial metabolites in mice. JCI Insight, 6(9): e145607. (*equal contribution)
14. Claesen J, JB Spagnolo, S Flores Ramos, KL Kurita, AL Byrd, AA Aksenov, AV Melnik, WR Wong, S Wang, RD Hernandez, MS Donia, PC Dorrestein, HH Kong, JA Segre, RG Linington, MA Fischbach, and KP Lemon (2020). A Cutibacterium acnes antibiotic modulates human skin microbiota composition in hair follicles. Sci Transl Med, 12(570): eaay5445.
This paper was featured in the AAAS Podcast “How microbes compete for space on our face“.
13. Bell A, J Brunt, E Crost, L Vaux, R Nepravishta, CD Owen, D Latousakis, A Xiao, W Li, X Chen, MA Walsh, J Claesen, J Angulo, GH Thomas, and N Juge (2019). Elucidation of a sialic acid metabolism pathway in mucus-foraging Ruminococcus gnavus unravels mechanisms of bacterial adaptation to the gut. Nat Microbiol, 4(12): 2393-2404.
12. Ozcam M, R Tocmo, JH Oh, A Afrazi, JD Mezrich, S Roos, J Claesen, and JP van Pijkeren (2019). The gut symbionts Lactobacillus reuteri R2lc and 2010 encode a polyketide synthase cluster that activates the mammalian aryl-hydrocarbon receptor. Appl Environ Microbiol, 85(10): e01661-18.
11. Claesen J (2018). Topical antiseptics and the skin microbiota. J Investig Dermatol, 138(10):2106-2107. (commentary)
Prior publications:
10. Ridaura V, N Bouladoux, J Claesen, E Chen, AL Byrd, M Constantinides, S Tamoutounour, MA Fischbach, and Y Belkaid (2018). Contextual control of skin immunity and inflammation by Corynebacterium. J Exp Med, 215(3): 785-799.
9. Smanski MJ, H Zhou, J Claesen, B Shen, MA Fischbach, and CA Voigt (2016). Synthetic biology to access and expand nature’s chemical diversity. Nat Rev Microbiol, 14(3): 135-149. (review)
8. Thanapipatsiri A, J Claesen, JP Gomez-Escribano, M Bibb, and A Thamchaipenet (2015). A Streptomyces coelicolor host for the heterologous expression of Type III polyketide synthase genes. Microb Cell Fact, 14(1): 145.
7. Medema MH, R Kottmann, P Yilmaz, M Cummings, JB Biggins, K Blin, I de Bruijn, YH Chooi, J Claesen, RC Coates, et al. (2015). Minimum information about a biosynthetic gene cluster. Nat Chem Biol, 11(9): 625-631.
6. Claesen J, and MA Fischbach (2015). Synthetic microbes as drug delivery systems. ACS Synth Biol, 4(4): 358-364. (review)
5. Wollenberg MS*, J Claesen*, IF Escapa, KL Aldridge, MA Fischbach, and KP Lemon (2014). Propionibacterium-produced coproporphyrin III induces Staphylococcus aureus aggregation and biofilm formation. mBio, 5(4): e01286-01214. (*equal contribution)
4. Cimermancic P*, MH Medema*, J Claesen*, K Kurita, LC Wieland Brown, K Mavrommatis, A Pati, PA Godfrey, M Koehrsen, J Clardy, BW Birren, E Takano, A Sali, RG Linington, and MA Fischbach (2014). Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters. Cell, 158(2): 412-421. (*equal contribution)
3. Claesen J, and MJ Bibb (2011). Biosynthesis and regulation of grisemycin, a new member of the linaridin family of ribosomally synthesized peptides produced by Streptomyces griseus IFO 13350. J Bacteriol, 193(10): 2510-2516.
2. Claesen J, and M Bibb (2010). Genome mining and genetic analysis of cypemycin biosynthesis reveal an unusual class of posttranslationally modified peptides. Proc Natl Acad Sci USA, 107(37): 16297-16302.
1. Goto Y, B Li, J Claesen, Y Shi, MJ Bibb, and WA van der Donk (2010). Discovery of unique lanthionine synthetases reveals new mechanistic and evolutionary insights. PLoS Biol, 8(3): e1000339.
Research News
Cleveland Clinic researchers find that despite general benefits from fruits and vegetables, people need the right gut microbiota to reap the benefits from flavonoids.
