Dr Jesmond Dalli
Reader in Molecular Pharmacology
Centre: Lipid Mediator Unit
Email: firstname.lastname@example.orgTelephone: +44(0) 20 7882 8263
Jesmond Dalli is a Reader in Molecular Pharmacology at the Barts and The London School of Medicine and Dentistry and Queen Mary College. He is also a Sir Henry Dale Fellow and the director of the Lipid Mediator Unit at the William Harvey Research Institute. He received a B.Sc (Hons) in chemistry and biology and an M.Sc in biology from the University of Malta. He then read for and completed a PhD at the William Harvey Research Institute, Queen Mary University of London with Prof. Mauro Perretti. Dr Dalli then moved to Prof. Charles N. Serhan’s laboratory at Harvard Medical school and the Brigham and Women’s Hospital where he held the position of Instructor. He was also the co-director with Prof. Serhan of two NIH funded lipid mediator metabololipidomics cores. He published over 80 peer-reviewed publications including publications in Nature Medicine, Immunity and Science Translation Medicine.
Memberships and awards
- Eicosanoid Research Foundation Young Investigator Prize
- British Pharmacological Society, British Society of Immunology, American Society for Investigative Pathology, William Harvey Young Investigator award, IADR/AADR William J. Gies Award
Dr Romain Colas, Dr Lucy Ly, Dr Raquel Marques, Ms Patricia Soares De Souza, Ms Mary Walker, Ms Kimberly De Freitas Pistorius.
Accelerating the resolution of joint inflammation and the regeneration of damaged tissues
Inflammatory arthritis is characterised by uncontrolled joint inflammation resulting in damaged bones and cartilage. Current therapies are aimed at controlling the inflammatory component, however they do not promote the repair and regeneration of damaged tissues. We have recently identified two novel families of endogenous mediators produced by leukocytes during self-limited inflammation and coined thriteen series resolvins (RvTn-3 DPA) and maresin conjugates in tissue regeneration (MCTR). These mediators activate the host response to clear damaged cells, counter-regulate the production of pro-inflammatory mediators and they protect organs during ongoing inflammation. Therefore, we are interested in identifying the mechanisms that RvTn-3 DPA and MCTR activate to promote the resolution of joint inflammation and joint regeneration.
Mechanisms in promoting the clearance of bacterial infections
When inflammation is self-contained it leads to efficient disposal of the invading pathogen and the reestablishment of tissue and organ function. Recent evidence demonstrates that termination (or resolution) of acute inflammation is an active process that is orchestrated by a novel genus of essential fatty acid-derived mediators, termed specialised pro-resolving mediators. Disruption in these pro-resolving pathways leads to delayed termination of infectious inflammation, failed resolution and is associated with poor prognosis in humans. We recently uncovered a novel family of pro-resolving mediators, produced during acute self-limited infections that promote bacterial clearance by phagocytes and tissue repair and regeneration. The formation of these mediators in human leukocytes is initiated by 17-lipoxygenation of docosahexaenoic acid and thus they were coined protectin conjugates in tissue regeneration (PCTR). PCTR1 is also central in regulating tissue resolution tone and host responses to infections promoting the uptake and killing of bacteria by phagocytes as well as regulating cellular trafficking. Tissue PCTR1 biosynthesis is regulated by the vagus nerve that via the neurotransmitter acetylcholine that upregulates the PCTR1 pathway in leukocytes. Of note, disruption of this pathway impairs the host innate immune response and bacterial clearance.
Using lipid mediator Profiling in dissecting disease mechanisms and patient stratification.
Disease processes vary from patient-to-patient this highlighting the need for the development of tools to facilitate patient identification and stratification in clinical medicine. Most of the biomarkers employed in clinical medicine today are molecules that are involved in the propagation of inflammation. This stems from the notion that inflammatory diseases, which form by-and-large the majority of diseases afflicting modern society, occur due to over production of inflammation-initiating molecules. Recent evidence demonstrates that inflammation is not always detrimental and that the body produces molecules, identified by our group and others and termed specialised pro-resolving mediators [SPM], which actively promote its termination. Failure by the body to produce these molecules is now thought to contribute to disease. Therefore we are using lipid mediator profiles to obtain an understanding of mechanisms that may lead to disease by as well as patient’s disease status. Together these may then be useful for identifying more effective therapeutic strategies and monitor treatment effectiveness.
- Dalli J, Chiang N, Serhan CN. Elucidation of novel 13-series resolvins that increase with atorvastatin and clear infections. Nat Med. 2015 Sep;21(9):1071-5.
- Chiang N, Dalli J, Colas RA, Serhan CN. Identification of resolvin D2 receptor mediating resolution of infections and organ protection. J Exp Med. 2015 Jul 27;212(8):1203-17.
- Dalli J, Ramon S, Norris PC, Colas RA, Serhan CN. Novel proresolving and tissue-regenerative resolvin and protectin sulfido-conjugated pathways. FASEB J. 2015 May;29(5):2120-360
- Dalli J, Kraft BD, Colas RA, Shinohara M, Fredenburgh LE, Hess DR, Chiang N, Welty-Wolf K, Choi AM, Piantadosi CA, Serhan CN. The Regulation of Proresolving Lipid Mediator Profiles in Baboon Pneumonia by Inhaled Carbon Monoxide. Am J Respir Cell Mol Biol. 2015 Sep;53(3):314-25.
- Abdulnour RE*, Dalli J*, Colby JK, Krishnamoorthy N, Timmons JY, Tan SH, Colas RA, Petasis NA, Serhan CN, Levy BD. Maresin 1 biosynthesis during platelet-neutrophil interactions is organ-protective. Proc Natl Acad Sci USA. 2014 Nov 18;111(46):16526-31.
- Dalli J, Chiang N, Serhan CN. Identification of 14-series sulfido-conjugated mediators that promote resolution of infection and organ protection. Proc Natl Acad Sci USA. 2014 Nov 4;111(44):E4753-61.
- Dalli J, Colas RA, Arnardottir H, Serhan CN. Vagal Regulation of Group 3 Innate Lymphoid Cells and the Immunoresolvent PCTR1 Controls Infection Resolution. Immunity. 2017 Jan 4. pii: S1074-7613(16)30514-3.
- Dalli J, Norling LV, Montero-Melendez T, Federici Canova D, Lashin H, Pavlov AM, Sukhorukov GB, Hinds CJ, Perretti M. Microparticle alpha-2-macroglobulin enhances pro-resolving responses and promotes survival in sepsis. EMBO Mol Med. 2014 Jan;6(1):27-42.
- Dalli J, Consalvo AP, Ray V, Di Filippo C, D'Amico M, Mehta N, Perretti M. Proresolving and tissue-protective actions of annexin A1-based cleavage-resistant peptides are mediated by formyl peptide receptor 2/lipoxin A4 receptor. J Immunol. 2013 Jun 15;190(12):6478-87.
- Dalli J, Winkler JW, Colas RA, Arnardottir H, Cheng CY, Chiang N, Petasis NA, Serhan CN. Resolvin D3 and aspirin-triggered resolvin D3 are potent immunoresolvents. Chem Biol. 2013 Feb 21;20(2):188-201
- Dalli J, Serhan CN. Specific lipid mediator signatures of human phagocytes: microparticles stimulate macrophage efferocytosis and pro-resolving mediators. Blood. 2012 Oct 11;120(15):e60-72
* denotes shared authorship