Dr. Peder Lund obtained a PhD in Immunology from Stanford and then completed post-doctoral training in epigenetics and mass spectrometry at the University of Pennsylvania and Washington University in St. Louis. Research in the Lund Lab generally focuses on how resident microbes in the gut, collectively known as the microbiota, interact with the host epithelium to promote homeostasis and how alterations in these interactions contribute to pathological states like Crohn’s disease and ulcerative colitis.
The gut epithelium forms a critical barrier that physically separates the microbiota from the underlying host tissue. In the absence of an intact epithelium, microbes may gain access to host tissues, possibly triggering an inflammatory response. While gut homeostasis may depend on physical compartmentalization of the microbiota and host, it also depends on symbiotic interactions between these two compartments. These interactions often occur through small molecule metabolites emanating from the microbiota, which are influenced by host diet and affect a broad range of processes including cell differentiation, nutrient absorption, epithelial barrier function, tumorigenesis, and inflammation. For instance, fermentation of dietary fiber by the microbiota generates butyrate and other short-chain fatty acids, which are thought to be the main sources of energy for epithelial cells via beta oxidation.
Now that sequencing approaches have revealed the composition of the microbiota and its genetic potential for small molecule production, complementary approaches to assess its functional output are needed to deepen our understanding of host-microbiota interactions and their role in health and disease. As a versatile platform for the high-throughput analysis of small molecules and proteins in both hypothesis-driven and hypothesis-generating research, mass spectrometry is ideally suited to accomplish this goal. Thus, a major endeavor in the Lund Lab is to apply mass spectrometry and other high-throughput approaches to determine which components of the microbial metabolome have a functional effect on host cells and then elucidate the pathways responsible for these effects. We are especially interested in how small molecules produced by microbes can serve as metabolic precursors and receptor ligands, thereby modulating energy balance and gene expression in host cells. Underscoring the clinical relevance of our work on energy homeostasis in the gut, ulcerative colitis has been associated with deficient beta oxidation in epithelial cells. Ultimately, we hope that our research will advance insight into the causes of inflammatory bowel disease and contribute to the development of new therapeutics.
Awards and Honors
Lund PJ*, Lopes M*, Sidoli S, Coradin M, Vitorino FNL, da Cunha JPC, Garcia BA. FGF-2 induces a failure of cell cycle progression in cells harboring amplified K-Ras, revealing new insights into oncogene-induced senescence. Mol Omics. 2021 Oct 11;17(5):725-739. doi: 10.1039/d1mo00019e. PubMed PMID: 34636387; PubMed Central PMCID: PMC8511509.
Lund PJ, Lehman SM, Garcia BA. Quantitative analysis of global protein lysine methylation by mass spectrometry. Methods Enzymol. 2019;626:475-498. doi: 10.1016/bs.mie.2019.07.036. Epub 2019 Aug 12. PubMed PMID: 31606088.
Lund PJ, Kori Y, Zhao X, Sidoli S, Yuan ZF, Garcia BA. Isotopic Labeling and Quantitative Proteomics of Acetylation on Histones and Beyond. Methods Mol Biol. 2019;1977:43-70. doi: 10.1007/978-1-4939-9232-4_5. PubMed PMID: 30980322; PubMed Central PMCID: PMC6543536.
Woo CM*, Lund PJ*, Huang AC, Davis MM, Bertozzi CR, Pitteri SJ. Mapping and Quantification of Over 2000 O-linked Glycopeptides in Activated Human T Cells with Isotope-Targeted Glycoproteomics (Isotag). Mol Cell Proteomics. 2018 Apr;17(4):764-775. doi: 10.1074/mcp.RA117.000261. Epub 2018 Jan 19. PubMed PMID: 29351928; PubMed Central PMCID: PMC5880114.
Lund PJ, Elias JE, Davis MM. Global Analysis of O-GlcNAc Glycoproteins in Activated Human T Cells. J Immunol. 2016 Oct 15;197(8):3086-3098. doi: 10.4049/jimmunol.1502031. Epub 2016 Sep 21. PubMed PMID: 27655845; PubMed Central PMCID: PMC5055199.