Skip to main content
The William Harvey Research Institute - Faculty of Medicine and Dentistry
  1. WHRI
  2. People
  3. Academic staff
  4. Items

Dr Trinidad Montero-Melendez

Trinidad

Senior Lecturer in Molecular Pharmacology

Centre: Biochemical Pharmacology

Email: t.monteromelendez@qmul.ac.uk
Telephone: +44(0) 20 7882 5644
Twitter: @TriniMonteroM

Profile

LinkedIn
Loop Research Network
ORCID iD: 0000-0002-3563-376X

Trinidad trained as a Pharmacologist and obtained her PhD in Biochemistry and Molecular Biology at the University of Granada, Spain. She later joined the William Harvey Research Institute to work on understanding the pro-resolving potential of melanocortin receptors. During that period, she discovered the pro-resolving activities of the molecule AP1189 and its novel biased mode of action, which entered clinical development shortly after.

In collaboration with several biotech and pharmaceutical companies, she has also contributed to the pre-clinical development of several other drug candidates for the treatment of inflammatory conditions and has participated in large high-throughput drug screening programmes for the identification of novel pro-resolving drugs. Another contribution to science includes the discovery of a novel mechanism of induction of senescence in synovial fibroblasts with therapeutic potential in diseases like rheumatoid arthritis. Her research is now focused on autoimmune diseases associated with chronic inflammation, and in developing innovative drugs that can target common mechanisms on autoimmune diseases.

Trinidad has published over 40 peer-reviewed publications as well as articles for the general public and children in the magazines The Biochemist and Frontiers for Young Minds. She also founded AutoImmunity Research Advisors (AIRA), a patient and public involvement and engagement group, focused on autoimmune diseases.

Trinidad is the teaching Lead on the module The Business of Pharmacology, on the Pharmacology and Innovative Therapeutics Program, has served as guest Associate Editor of several journals and sat at funding panels, among other contributions.

Other Roles:

Research

Group members

Drug Discovery and Development – Resolution Pharmacology

Melanocortin (MC) agonists are part of the Resolution Pharmacology concept which postulates that therapeutic strategies focused on the active promotion of our body’s endogenous pro-resolving mechanisms may lead to better and safer drugs. Melanocortin ligands act on five different MC receptors (MC1-5), which belong to the G-protein couple receptors (GPCR) family. Their GPCR nature, wide-spread tissue distribution and participation in multiple biological processes, make these receptors highly druggable. Indeed, a few MC compounds are now approved for clinical use for conditions like erythropoietic protoporphyria (EPP) or for severe obesity.

In our lab, we work on the development of new compounds targeting the MC system, either by running our own drug development pipelines, or in close collaboration with industrial partners, by contributing to target characterization, identification of mode of actions or conducting pre-clinical evaluation of novel candidates.

Common Mechanisms to Autoimmune Diseases

Autoimmune diseases (AD), like rheumatoid arthritis or lupus, do not come alone. Chances are that 1 out of 4 patients suffering from an AD will develop additional ones throughout their lives. Better understanding of the shared causes across different ADs will not only increase our knowledge on why these diseases occur together but could also guide the development of new therapies that could be effective across several ADs.

The melanocortin peptide adrenocorticotropin hormone (ACTH) can be used to treat several ADs including rheumatoid arthritis and multiple sclerosis, although its use is very limited because ACTH also activates the stress hormone ‘cortisol’, causing serious side effects. In our lab we work to create novel melanocortin agonists devoid of those side effects so that these drugs could be safely used for long-term chronic inflammatory conditions which are typically associated with ADs, like for example rheumatoid arthritis, fibrosis or inflammatory bowel disease.

Melanocortins, senescence and tissue repair

Over the last 15 years, we have advanced the field on melanocortin research by discovering the pro-resolving actions of melanocortin agonists and by contributing to the identification of novel modes of action of MC drugs, including allosteric modulation or biased agonism.

More recently, we discovered a new action of a selective MC1 agonist which is the induction of a cellular senescence-like phenotype in aberrantly activated fibroblasts, favouring the resolution of inflammation in models of arthritis and the acquisition of a pro-repair phenotype.

We are currently investigating the detailed mode of action of this novel mechanism and exploring other conditions for therapeutic application to scale up the translational impact of this discovery.

Pharmacogenomics and Precision Medicine

The melanocortin receptor MC1 is encoded by a highly polymorphic gene for which more than 900 genetic variants (SNPs) have been identified. MC1 is highly expressed in melanocytes, the skin cells responsible for the production of melanin. Many of these variants cause a loss-of-function on the receptor leading to reduced production of melanin. MC1 gene variation is responsible for the diversity in human normal pigmentation, reflected in skin and hair colour, and it is strongly associated with red hair. MC1 is mainly responsible for the tanning response upon UV stimulation, and it is strongly associated with skin cancer risk. However, the high frequency of these variants in the population may impact on the development of MC1- based therapies.

We are investigating what is the impact of carrying a variant on MC1R gene on the anti-inflammatory properties of melanocortin drugs to find out if precision medicine approaches based on MC1R genotype would provide better therapeutic options by ensuring giving the right drug to the right patient.

Publications

Full list of publications

    • Davan-Wetton CSA, Montero-Melendez T*. An optimised protocol for the detection of lipofuscin, a versatile and quantifiable marker of cellular senescence. PLOS ONE Protocols 2024, 19(7):e0306275. doi: 10.1371/journal.pone.0306275.
    • Thomas BL, Montero-Melendez T, Oggero S, Kaneva MK, Chambers D, Pinto AL, Nerviani A, Lucchesi D, Austin-Williams S, Hussain MT, Pitzalis C, Allen B, Malcangio M, Dell'Accio F, Norling LV, Perretti M. Arthritis & Rheumatology 2024, doi: 10.1002/art.42958.
    • Garrido-Mesa J, Thomas BL, Dodd J, Spana C, Perretti M, Montero-Melendez T* Pro-resolving and anti-arthritic properties of the MC1 selective agonist PL8177. Frontiers in Immunology 2022, doi: 10.1002/art.42958.
    • Montero-Melendez T*, Nagano A, Chelala C, Filer A, Buckley CD, Perretti M. Therapeutic senescence via GPCR activation in synovial fibroblasts facilitates resolution of arthritis. Nature Communications 2021, 11(1):745.
    • Patruno S, Garrido-Mesa J, Romano M, Perretti M, Montero-Melendez T*. Ligand bias and its association with pro- resolving actions of melanocortin drugs. Frontiers in Pharmacology 2018, 9:919. doi: 10.3389/fphar.2018.00919
    • Montero-Melendez T*, Forfar RA, Cook JM, Jerman JC, Taylor DL, Perretti M. Old drugs with new skills: fenoprofen as an allosteric enhancer at melanocortin receptor 3. Cellular and Molecular Life Sciences 2017,74(7):1335-1345.
    • Haas R, Smith J, Rocher-Ros V, Nadkarni S, Montero-Melendez T, D'Acquisto F, Bland EJ, Bombardieri M, Pitzalis C, Perretti M, Marelli-Berg FM, Mauro C. Lactate Regulates Metabolic and Pro-inflammatory Circuits in Control of T Cell Migration and Effector Functions. PLoS Biology. 2015 Jul 16;13(7):e1002202.
    • Montero-Melendez T*, Gobbetti T, Cooray SN, Jonassen TEN, Perretti M. Biased agonism as a novel strategy to harness the pro-resolving properties of melanocortin receptors without eliciting melanogenic effects. The Journal of Immunology. 2015;194(7):3381-8.
    • Montero-Melendez T*, Fernandes Moreira Madeira M, Norling LN, Alsam A, Curtis MA, da Silva TA, Perretti M. Association between periodontal disease and inflammatory arthritis reveals modulatory functions by melanocortin receptor type 3. American Journal of Pathology 2014;184(8):2333-41.
    • Dalli J, Norling LV, Montero-Melendez T, Canova DF, Lashin H, Pavlov AM, Sukhorukov GB, Hinds CH, Perretti M. Microparticle alpha-2-macroglobulin enhances pro-resolving responses and promotes survival in sepsis. EMBO Mol Med 2014;6(1):27-42
    • Cooray SN, Gobbetti T, Montero-Melendez T, McArthur S, Thompson D, Clark AJL, Flower RJ, Perretti M. Ligand- specific activation of ALX/FPR2: identification of conformational changes associated with pro-resolving functional responses. PNAS 2013;110(45):18232-7.
    • Dalli J*, Montero-Melendez T* ,Norling LV, Yin X, Hinds C, Haskard D, Mayr M, Perretti M. Heterogeneity in neutrophil microparticles reveals distinct proteome and functional properties. Mol Cell Proteomics 2013, 12(8):2205- 2219 (*share first authorship)
    • Montero-Melendez T*, Dalli J, Parretti M. Gene expression signature based approach identifies a pro-resolving mechanism of action for histone deacetylase inhibitors. Cell Death Differ 2013;20(4):567-575.
    • Montero-Melendez T*, H.B. Patel, M. Seed, S. Nielsen, T. Jonassen, M. Perretti. The melanocortin agonist AP214 exerts anti-inflammatory and pro-resolving properties: evidence for a major involvement of the melanocortin receptor type 3. American Journal of Pathology 2011, 179(1):259-269.

    Science communication to the general public:

    • Editor of AIRA Magazine (Science news for patients with autoimmune diseases).
    • Montero-Melendez T. May inflammation be with you! Frontiers for Young Minds 2018, 6:51. doi: 10.3389/frym.2018.00051
    • Perretti M, Montero-Melendez T. Resolution in an ‘over-inflamed era’. The Biochemist 2017, 39(4):4-7.

    Sponsors

    Collaborators

    Internal

    External

    • Prof David Abraham (UCL)
    • Prof Andrew Filer (University of Birmingham)
    • Prof Thomas Jonassen (University of Copenhagen)

    News

    Teaching

    Module Lead

    Lecturer

    Other

    • PBL Tutor
    • Academic Advisor

    Disclosures

    • 2021 - current: Received research funds from SynAct Pharma AB
    • 2020 - current: Performed expert consultancy activity for SynAct Pharma AB
    • 2019: Performed expert consultancy activity for NeuroCreate Ltd (QConsult)
    • 2018: Performed expert consultancy activity for Palatin Technologies Inc
    • 2017- 2018: Performed expert consultancy activity for ResoTher Pharma
    • 2016: Performed expert consultancy activity for Mallinckdrodt Pharmaceuticals
    Back to top