Episode 14 Dr Kate Macnamara SPMs, Bone Marrow Failure & the Resolution of Inflammation in Hematopoiesis

Dr. Oliver Werz "Rewiring the Inflammatory Cascade: Lipoxygenase Pathways, Natural Products & SPMs with Prof. Oliver Werz"Show NotesIn this episode of the Specialized Pro-Resolving Mediators Podcast our guest is Professor Dr. Oliver Werz, Head of the Department of Pharmaceutical and Medicinal Chemistry at Friedrich Schiller University Jena. Prof. Werz is a leading researcher at the intersection of pharmaceutical chemistry, lipid mediator biology, and inflammation resolution. Dr. Werz trained as a pharmacist, completed his doctorate on the enzyme 5-lipoxygenase at the University of Tübingen, and later worked with Nobel laureate Bengt Samuelsson at the Karolinska Institute. He also spent time in Charles Serhan’s laboratory, deepening his focus on specialized pro-resolving mediators (SPMs). In this conversation we discuss: • His early interest in chemistry and biology and the path that led him into pharmacy and lipid mediator research • Formative experiences with Bengt Samuelsson and Charles Serhan • Landmark work showing how human M1 and M2 macrophages produce distinct lipid mediator profiles in response to bacteria (including the 2018 Nature Communications study with Charles Serhan) • How natural products such as boswellic acids, cannabidiol, and rosemary-derived compounds can shift cells away from pro-inflammatory leukotrienes toward specialized pro-resolving mediators • Research on key enzymes (5-lipoxygenase, FLAP, 15-lipoxygenase) • Sex differences in leukotriene and SPM production • Strategies to promote endogenous resolution of inflammation • How his large lab in Jena is organized across biosynthesis, bioanalysis, cell-to-cell communication, and drug discoveryM1 vs M2 macrophages & bacterial pathogens Werz O. et al. (2018). Human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity. Nature Communications. https://www.nature.com/articles/s41467-017-02538-5 Boswellic acids (frankincense) & allosteric modulation of lipoxygenases Börner F. et al. (2023). Allosteric Activation of 15-Lipoxygenase-1 by Boswellic Acid Induces the Lipid Mediator Class Switch to Promote Resolution of Inflammation. Advanced Science. https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202205604 Cannabidiol as a molecular switch for SPM biosynthesis Peltner L.K. et al. (2023). Cannabidiol acts as molecular switch in innate immune cells to promote the biosynthesis of inflammation-resolving lipid mediators. Cell Chemical Biology. https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(23)00249-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2451945623002490%3Fshowall%3Dtrue Uncovering anti-inflammatory natural products that synergize with supplemented omega-3 PUFA for eliciting endogenous inflammation resolution signals Paul M. Jordan, Lukas K. Peltner, … Oliver Werz Biomedicine & Pharmacotherapy (2025) https://www.sciencedirect.com/science/article/pii/S0753332225003841)

"Synthesizing Resolution:Protectins, Stereochemistry & the Chemistry of SPMs" with Professor Trond Vidar Hansen, Professor of Pharmaceutical Chemistry at the University of Oslo,for a deep dive into the synthetic chemistry that underpins specialized pro-resolving mediator (SPM) research.Professor Hansen is a leading figure at the intersection of organic synthesis and lipid mediator biology. His laboratory specializes in the stereoselective total synthesis of SPMs — particularly the protectin family and n-3 docosapentaenoic acid (n-3 DPA)-derived resolvins, protectins, and maresins — as well as the design of metabolically more stable analogs such as 3-oxa-PD1n-3 DPA.Through close collaborations with Charles Serhan and other pioneers in the field, his group has provided authentic, stereochemically pure SPMs that have enabled critical biological and translational studies in inflammation resolution, pain, itch, and tissue protection.In this conversation we explore:How an early interest in chemistry and work on insect-derived oxygenated polyunsaturated fatty acids led him into the world of SPMsThe critical importance of stereochemistry and why total synthesis has been essential for confirming SPM structuresThe unique chemistry and biology of protectins and n-3 DPA-derived mediatorsWhy protectins/neuroprotectins appear especially relevant in immunoprivileged tissues such as the brain and eyesThe challenges of synthesizing highly unsaturated, chemically sensitive lipid mediators (conjugated trienes and tetraenes)Design and biological evaluation of the more stable 3-oxa-PD1n-3 DPA analog in pain and itch modelsAutacoid properties of SPMs — local, on-demand action and the difficulty of measuring them in plasmaWhy these mediators work at nanomolar and even picomolar concentrationsThe concept of resolution pharmacology and the translational potential of SPM analogs versus omega-3 precursorsReflections on collaborations with chemists such as Nicos Petasis, Bernd Spur, and Charles SerhanWhether you are a chemist, biologist, clinician, or simply fascinated by how the body actively resolves inflammation, this episode offers a rare look at the synthetic work that makes modern SPM research possible.Papers mentioned:Total Synthesis of the Lipid Mediator PD1n-3 DPA (2014)https://pubs.acs.org/doi/10.1021/np4009865Total Synthesis of MaR1n-3 DPA Utilizing an sp³–sp³ Negishi Cross-Coupling (2014)https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.201404721Free full text: https://pmc.ncbi.nlm.nih.gov/articles/PMC4232850/The Protectin Family of Specialized Pro-resolving Mediators (2019 review)https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.01582/fullA new synthetic protectin D1 analog 3-oxa-PD1n-3 DPA reduces neuropathic pain and chronic itch (2021)https://pubs.rsc.org/en/content/articlelanding/2021/ob/d0ob02136aBiology and Total Synthesis of n-3 Docosapentaenoic Acid-Derived Specialized Pro-Resolving Mediators (2024 review)https://www.mdpi.com/1420-3049/29/12/2833

Episode 16 Dr. Denise Biagini, "Measuring the Molecules of Resolution: Dr. Denise Biagini on Quantifying SPMs & Oxylipins"Guest Dr. Denise Biagini Department of Chemistry and Industrial Chemistry University of Pisa, Italy University profile: https://www.unipi.it/en/about-us/organisation/people/denise-biagini-146879-en/Key Topics Discussed • Early interest in science and the path into analytical chemistry • Turning point: PhD project on prostaglandins/isoprostanoids in dried blood spots from premature infants (patent ductus arteriosus) • Research stay at the Metabolomics Innovation Centre (Edmonton) with Rupasri Mandal and David Wishart • Encountering the work of Charles Serhan and the concept of SPMs from an analytical chemist’s perspective • Development of MEPS-UHPLC-MS/MS platforms for large oxylipin/SPM panels • Analytical challenges (stability, matrix effects, low concentrations, DBS sampling) • Findings in COVID-19 (lower pro-resolving mediators in more severe patients) • Applications in heart failure (saliva), ultramarathon runners (urinary EVs), and neonatal care • What “lipid mediator class switching” and failed resolution look like in real human samples • Future potential of non-invasive SPM monitoringPapers Referenced / Key Publications • MS-based targeted profiling of oxylipins in COVID-19: A new insight into inflammation regulation Free Radical Biology and Medicine (2022) https://www.sciencedirect.com/science/article/pii/S0891584922000326 Open access (PMC): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8786407/ • A MEPS-UHPLC-MS/MS analytical platform to detect isoprostanoids and specialized pro-resolving mediators in the urinary extracellular vesicles of mountain ultramarathon runners Talanta (2024) https://www.sciencedirect.com/science/article/abs/pii/S0039914024009986 • Salivary lipid mediators: Key indexes of inflammation regulation in heart failure disease Free Radical Biology and Medicine (2023) https://www.sciencedirect.com/science/article/pii/S089158492300120X • Micro-extraction by packed sorbent combined with UHPLC-ESI-MS/MS for the determination of prostanoids and isoprostanoids in dried blood spots Talanta (2020) https://pubmed.ncbi.nlm.nih.gov/31514837/ DOI: 10.1016/j.talanta.2019.120236 • Methodological aspects of dried blood spot sampling for the determination of isoprostanoids and prostanoids Microchemical Journal (2022) https://www.sciencedirect.com/science/article/abs/pii/S0026265X22000406 • Related follow-up: The effect of SARS-CoV-2 variants on the plasma oxylipins and PUFAs of COVID-19 patients Prostaglandins & Other Lipid Mediators (2023) https://www.sciencedirect.com/science/article/abs/pii/S1098882323000679

Episode 15 Dr. Matthew Spite: "Resolvins, Vascular Inflammation & the Power of Resolution Biology"In this episode of the SPM Podcast, we welcome Dr. Matthew Spite, Associate Professor at Harvard Medical School and Lead Investigator of the Spite Lab in the Center for Experimental Therapeutics and Reperfusion Injury (CETRI) at Brigham and Women’s Hospital.Dr. Spite is a leading expert in specialized pro-resolving mediators (SPMs), vascular biology, and inflammation resolution. During his postdoctoral training in Charles Serhan’s laboratory, he contributed to the structural and functional elucidation of key SPMs, including Resolvin D2 (RvD2) and Maresin 1 (MaR1).His independent research investigates how these mediators and their receptors regulate innate immunity, limit vascular inflammation and atherosclerosis, support tissue repair and revascularization, and influence metabolic health including studies on adipose tissue SPM biosynthesis, exercise, brown adipose tissue activation, and RvD2 signaling via the GPR18 receptor on myeloid cells.In this conversation we discuss:• Early interests (music vs. science) and the path from chemistry at Indiana University to biophysics/physiology at the University of Louisville• Mentorship under Arun Bhatnagar and first exposure to lipid biochemistry and mass spectrometry• Discovering Charles Serhan’s work and joining the lab that was rewriting the paradigm of inflammation• Contributions to the early characterization of Resolvin D2 and Maresin 1• Current focus of the Spite Lab at Harvard / BWH / CETRI• SPMs in vascular inflammation, atherosclerosis, and post-ischemic tissue repair• Resolvin biosynthesis in adipose tissue, effects of exercise, and brown fat activation• RvD2–GPR18 signaling in myeloid cells• Translational potential of resolution pharmacology for chronic inflammatory and cardiovascular diseases• Balancing independent research, mentoring, and collaboration• Personal side and what keeps him groundedKey PapersFoundational SPM elucidations (Serhan Lab era)• Spite M, Norling LV, Summers L, et al. Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. Nature. 2009;461(7268):1287–1291.https://pmc.ncbi.nlm.nih.gov/articles/PMC2779525/• Serhan CN, Yang R, Martinod K, Kasuga K, Pillai PS, Porter TF, Oh SF, Spite M. Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions. Journal of Experimental Medicine. 2009;206(1):15–23.https://rupress.org/jem/article/206/1/15/54203/Maresins-novel-macrophage-mediators-with-potentTissue repair / Muscle regeneration• Giannakis N, Sansbury BE, Patsalos A, et al. Dynamic changes to lipid mediators support transitions among macrophage subtypes during muscle regeneration. Nature Immunology. 2019;20(5):626–636.https://www.nature.com/articles/s41590-019-0356-7Vascular / Atherosclerosis & GPR18 signaling• Lipscomb M, Walis S, Marinello M, Mena HA, MacNamara KC, Spite M, Fredman G. Resolvin D2 limits atherosclerosis progression via myeloid cell-GPR18. FASEB Journal. 2024;38(6):e23555.https://pmc.ncbi.nlm.nih.gov/articles/PMC12679858/

Episode 14 Dr. Kate MacNamara: SPMs, Bone Marrow Failure & the Resolution of Inflammation in HematopoiesisIn this episode of the SPM Podcast, we welcome Dr. Katherine C. (Kate) MacNamara, Professor of Immunology and Microbial Disease at Albany Medical College and leader of the MacNamara Lab.Dr. MacNamara’s research focuses on how the hematopoietic system responds to and recovers from infection, inflammation, aging, and bone marrow failure. She has brought Specialized Pro-Resolving Mediators (SPMs) into the center of this field, showing how resolution pathways shape macrophage function, hematopoietic stem cell behavior, and recovery of blood cell production.In this conversation we explore:• How SPMs entered her research and why resolution biology is critical for the bone marrow niche • The lipid mediator class switch and the balance between initiation and resolution of inflammation in hematopoiesis • Efferocytosis as a key SPM-linked process in the marrow • Her landmark work on Resolvin E1 (RvE1) in severe aplastic anemia: how it improves efferocytosis, rescues marrow function, and what lipidomics revealed about impaired SPM pathways • Radiation- and infection-induced stress, macrophage senescence, and the protective roles of SPMs such as Resolvin D1• Her collaboration with Dr. Gabrielle Fredman on SPM biology in aging, atherosclerosis, and inflammaging (including their joint NHLBI R01) • How aged or senescent marrow macrophages drive pathology — and how SPMs can help restore balance • Therapeutic potential of SPMs and analogs for bone marrow failure and cardiovascular disease without broad immunosuppression • Challenges and opportunities in translating resolution pharmacology to hematology and immunologyLinks & ResourcesKey paper: Resolvin E1 improves efferocytosis and rescues severe aplastic anemia in mice (Cell Death & Disease, 2024) https://www.nature.com/articles/s41419-024-06705-7Paper Aplastic anemia Resolvin E1 Cyclosporin A paper with Dr. Rachel Grazdahttps://pmc.ncbi.nlm.nih.gov/articles/PMC11082201/Paper about Radiation- and infection-induced stress, macrophage senescence, and the protective roles of SPMs such as Resolvin D1 https://pmc.ncbi.nlm.nih.gov/articles/PMC8555670/MacNamara Lab X/Twitter: @MacNamaraLab

Dr Alpdogan KantarciEpisode 12 Dr. Alpdogan Kantarci “SPMs in Oral Inflammation & Periodontal Regeneration: Resolution Biology, Host Modulation & Systemic Links”In this episode we welcome Professor Dr. Alpdogan Kantarci, a leading voice in inflammation resolution biology and one of the foremost experts exploring how Specialized Pro-resolving Mediators actively resolve inflammation in the oral mucosa and beyond.We discuss his career path from Istanbul University to postdoctoral and specialty training at Boston University, his long-standing work at the Forsyth Institute and Harvard, and his current role as Erwin M. Schaffer Chair and Department Chair at the University of Minnesota. The conversation covers foundational research on SPMs (especially Resolvin E1 and Maresin-1) in periodontitis, tissue and bone protection, reversal of cellular senescence, restoration of immune homeostasis, microbiome rebalancing, pro-resolving nanomedicines, and the translational shift toward host-modulation therapies.Key themes include the unique clinical-translational perspective he brings as both periodontist and researcher, the power of SPMs to regenerate rather than merely suppress damage, challenges and opportunities in moving resolution pharmacology into everyday dentistry, and the growing links between oral inflammation and systemic conditions such as neurodegenerative disease.Key Topics • Career journey from Istanbul to Boston, Forsyth, Harvard, and the University of Minnesota • What SPMs are and how RvE1 & MaR1 protect against local tissue and bone destruction • Reversing senescence-related dysfunction in periodontal ligament cells and stem cells • Failed resolution, T-cell/Th17 imbalance, and restoring homeostasis without immunosuppression • Breaking the inflammatory–dysbiosis vicious cycle and reshaping the oral microbiome • Pioneering pro-resolving nanomedicines with benzo-lipoxin A4 for hard- and soft-tissue regeneration • Preclinical evidence of bone regeneration and restored periodontal ligament stem-cell function • Why host-modulation with nanotechnology represents the future of clinical dentistry • Oral–systemic connections, including links to neurodegenerative disease • Translational outlook for resolution-based therapies in periodontology

Episode 12 Dr. Marc Dubourdeau“From Bench to Biotech: SPM Lipidomics, Resolution Biology & Nutritional Innovation with Dr. Marc Dubourdeau”In this episode we welcome Dr. Marc Dubourdeau, a pioneering scientist and entrepreneur who has been at the forefront of turning SPM research into practical tools for human and animal health. We discuss his journey from immunology and macrophage research in Toulouse and the Institut Pasteur to founding Ambiotis, one of the world’s first contract research organizations dedicated to inflammation resolution and SPM biology. The conversation covers advanced lipidomics platforms, preclinical models across cystic fibrosis, chronic lung disease, cardiovascular conditions, veterinary applications, and skin/aging, his collaborations with Charles Serhan (including contributions to the Atlas of Inflammation Resolution), and the translation of this science into nutritional innovations such as optimized omega-3 blends designed to support endogenous SPM production.Key themes include the shift from classical anti-inflammatory thinking to active resolution biology, the power of precise lipid mediator measurement, and what resolution pharmacology and nutrition can mean for chronic disease and everyday wellness.───Key Topics • Early fascination with how the body works and path into immunology • PhD research on monocytes, macrophages, prostaglandins, leukotrienes, and lipid pathways • Work at the Institut Pasteur on macrophage–fungus interactions (Aspergillus) in cystic fibrosis and transplantation • Founding of Ambiotis as a specialized CRO for resolution biology and SPM lipidomics • Development of advanced analytical platforms and disease models • Collaborations with Charles Serhan and contributions to the Atlas of Inflammation Resolution • Applications ranging from lung disease and cardiovascular models to veterinary and skin/aging research • Translation into nutritional products that support the body’s natural SPM production • The broader implications of resolution pharmacology for chronic inflammation and wellness ───About the Guest Dr. Marc Dubourdeau earned his PhD in immunology from Université Paul Sabatier in Toulouse and conducted research at the Institut Pasteur in Paris. In 2007 he founded Ambiotis, a pioneering contract research organization focused on inflammation resolution and specialized pro-resolving mediator biology. He currently also leads Laboratoire Aloméa, translating SPM science into nutritional innovations.

Episode 11 Dr. Joan ClàriaIn this episode we welcome Professor Dr. Joan Clària, a leading voice in inflammation resolution biology and one of the pioneers exploring how the body actively resolves inflammation through lipid mediators. We discuss his career path from clinical biochemistry at Hospital Clínic Barcelona to postdoctoral work with Charles Serhan, his foundational research on SPMs in liver disease and obesity, the role of resolution deficits in adipose tissue inflammation and metabolic-associated fatty liver disease (MAFLD/MASH), and the translational potential of SPMs, omega-3 precursors, and stable analogs. Key themes include the unique clinical-biochemical perspective he brings to SPM biology, the importance of on-site SPM production in tissues, challenges in reversing established fibrosis, the need for more research on SPMs and adaptive immunity, and the future of resolution pharmacology for chronic metabolic and liver conditions.Key Topics • Early interest in mechanisms and clinical biochemistry training • Postdoctoral work with Charles Serhan (1992–1995) and discovery of aspirin-triggered lipoxins • Establishing a lab focused on lipid mediators in liver disease • First demonstrations of SPM deficits in obese adipose tissue and links to hepatic steatosis • Macrophage polarization, crown-like structures, and unresolved inflammation in obesity • SPMs, efferocytosis (including maresin 1 and Kupffer cells), and infection susceptibility in cirrhosis • Limitations of SPMs for established fibrosis and emphasis on prevention • Adaptive immunity, B-cell responses, and lessons from COVID-era observations • Current supplements vs. future stable analogs and receptor-targeted approaches • Personal life, family farm, and return to acute-on-chronic liver failure research About the Guest Professor Joan Clària is Professor at the University of Barcelona and Group Leader of the Inflammation and Liver Disease research group at IDIBAPS, Hospital Clínic de Barcelona. A clinical biochemist by training with extensive translational experience, he has published widely on pro-resolving mediators in liver disease, obesity, and metabolic inflammation and is a highly cited researcher in the field of inflammation resolution.

Episode 10 Dr Mauro Perretti“Immunoresolvents & Resolution Pharmacology: From Annexin A1 to SPMs with Dr. Mauro Perretti”In this episode we welcome Professor Mauro Perretti, a leading pioneer in immunopharmacology and the biology of inflammation resolution. We discuss his career path from Florence to the William Harvey Research Institute, his foundational work on Annexin A1, his collaboration with Charles Serhan, the concept of immunoresolvents, Specialized Pro-resolving Mediators (SPMs), neutrophil microvesicles, and the emerging field of resolution pharmacology. Key themes include why inflammation is not inherently “bad,” what mainstream medicine still overlooks, the therapeutic potential of SPMs and Annexin A1 in arthritis and chronic inflammation, mentorship of prominent researchers (including Jesmond Dalli and Lucy Norling), and the future of treatments that actively promote resolution rather than only suppress inflammation.Key Topics • Early career and entry into inflammation research • Meeting Charles Serhan in Florence and long-term collaboration • Annexin A1 biology and its multiple pro-resolving actions • Convergence of Annexin A1 and SPMs (shared ALX/FPR2 receptor) • Immunoresolvents and active resolution of inflammation • Resolution as a programmed process (apoptosis, efferocytosis, macrophage phenotype switch) • Limitations of drugs that only block the initiation phase of inflammation • Resolution pharmacology and potential in rheumatoid arthritis • Mentorship of key SPM scientists • Biological redundancy and resilience in resolution networksAbout the Guest Professor Mauro Perretti is a highly cited researcher (over 46,000 citations) whose work bridges Annexin A1, SPMs, neutrophil biology, and translational resolution pharmacology. He has held senior leadership roles at the William Harvey Research Institute and Queen Mary University of London.

Episode 9 Dr. Thomas E. Van Dyke, a world-renowned periodontist, researcher, and leader in inflammation resolution biology.Dr. Van Dyke earned his DDS from Case Western Reserve University in 1973, followed by an MS in Oral Sciences, Certificate in Periodontology, and PhD in Oral Biology from SUNY Buffalo in the early 1980s. He built his early career at Boston University,Rising to Professor and Director of Periodontology Research and Clinical Research programs, before joining the Forsyth Institute in 2010—where he now serves as Senior Vice President for Clinical and Translational Research and holds a professorship at Harvard School of Dental Medicine.Throughout his career, Dr. Van Dyke has focused on the pathogenesis of periodontal disease, with groundbreaking work on neutrophil biology, host responses, and the critical role of failed inflammation resolution in chronic tissue and bone destruction.His long-standing collaboration with Dr. Charles Serhan helped pioneer the application of specialized pro-resolving mediators—or SPMs—such as lipoxins and resolvins to oral health. This research is transforming how we think about treating periodontitis—not just by blocking inflammation, but by actively promoting its natural resolution and tissue regeneration.Dr van Dyke has also mentored many leading scientists in the field, including Drs. Gabrielle Fredman, Alpdogan Kantarci, and Hatice Hasturk, who continue to advance SPM research and its clinical applications.