Principal Investigator
Mitochondrial Medicine for Liver Disease
Contact Dr. Elena Palma: e.palma@researchinliver.org.uk
Dr Elena Palma graduated in “Pharmaceutical Chemistry and Technology” from the University of Padova (Italy), where she also obtained a PhD in Cellular Biology. She has been working in the field of Hepatology for almost fifteen years and is the Principal Investigator of the Mitochondrial Medicine for Liver Disease Lab at the Institute.
Research
The Palma Lab’s mission is to develop novel multi-pronged treatments for liver diseases, especially Alcohol-related Liver Disease (ALD) and liver cancers. The approach of the group is to advance translational experimental models to dissect complex disease processes (fibrosis, inflammation, hepatotoxicity and liver regeneration) to enhance drug discovery and preclinical efficacy and investigate the role of mitochondria in liver diseases to create targeted interventions.
Projects:
Advancement of human immunocompetent organotypic models of liver diseases and malignancies These are based on the culture of patient-derived Precision Cut Liver or Tumour Slices and the project aims at optimising reproducible and consistent methods for the application of slices in preclinical drug screening and investigations of complex disease processes.
Study of the role of mitochondria in ArLD and development of novel therapeutic strategies
The focus is on the impact of alcohol toxicity on mitochondrial dynamics and morphology, especially in the intriguing and controversial phenomenon of megamitochondria. The definitive objective will be to target mitochondria as a therapy for ArLD.
Investigation of the role of cyclophilins in liver disease and primary liver cancers
Preclinical data and clinical trials indicate cyclophilin inhibitors as a promising therapy for multiple diseases and our study aims at further dissecting their mechanisms of action in hepatic fibrosis, ALD, Hepatocellular Carcinoma and Cholangiocarcinoma.
Development of novel therapies for primary liver cancer
The main approaches include developing therapies targeting the tumour microenvironment and their preclinical testing in in vitro cellular systems or ex vivo patient-derived models.
Key collaborations:
In collaboration with Dr Luca Urbani:
1. Investigation of the role of cyclophilin inhibition in hepatic fibrosis and ALD;
2. Study of mitochondria regulation in Hepatic Stellate Cells activation;
3. Effect of immunotherapy in combination with anti-fibrotic in CCA.
In collaboration with Prof Michele Vacca:
Application of Precision Cut Liver Slices for the study of the effects of polyphenols in metabolic dysfunction-associated steatotic liver disease (MASLD).
In collaboration with Prof Shilpa Chokshi:
Testing the efficacy of immunomodulatory therapies in Precision Cut Tumour Slices from Hepatocellular Carcinoma.
Team:
Una Rastovic (PhD student)
Ravi Jagatia (PhD student)
Sergio Francesco Bozzano (RA)
Moyosoreoluwa Feyide (RA)
Bhavanaa Arunakumar (MSc student)
Selected Publications:
Rastovic U, Bozzano SF, Riva A, Simoni-Nieves A, Harris N, Miquel R, Lackner C, Zen Y, Zamalloa A, Menon K, Heaton N, Chokshi S, Palma E. (2023) Human Precision-Cut Liver Slices: A Potential Platform to Study Alcohol-Related Liver Disease. Int J Mol Sci. 2023 Dec 21;25(1):150. 10.3390/ijms25010150
Jagatia R, Doornebal EJ, Rastovic U, Harris N, Feyide M, Lyons AM, Miquel R, Zen Y, Zamalloa A, Malik F, Prachalias A, Menon K, Boulter L, Eaton S, Heaton N, Phillips S, Chokshi S, Palma E. (2023) Patient-derived precision cut tissue slices from primary liver cancer as a potential platform for preclinical drug testing. EBioMedicine 2023 Nov;97:104826. 10.1016/j.ebiom.2023.104826
Doornebal, E. J., Harris, N., Riva, A., Jagatia, R., Pizanias, M., Prachalias, A., Menon, K., Preziosi, M., Zamalloa, A., Miquel, R., Zen, Y., Orford, M. R., Eaton, S., Heaton, N., Ramage, J., Palma, E.*, Srirajaskanthan, R.*, & Chokshi, S.* (2022). Human Immunocompetent Model of Neuroendocrine Liver Metastases Recapitulates Patient-Specific Tumour Microenvironment. Frontiers in Endocrinology, 13. https://doi.org/10.3389/FENDO.2022.909180
Palma, E., Riva, A., Moreno, C., Odena, G., Mudan, S., Manyakin, N., Miquel, R., Degré, D., Trepo, E., Sancho-Bru, P., Altamirano, J., Caballeria, J., Zamalloa, A., Menon, K., Heaton, N., Williams, R., Bataller, R., & Chokshi, S. (2020). Perturbations in Mitochondrial Dynamics Are Closely Involved in the Progression of Alcoholic Liver Disease. Alcoholism, Clinical and Experimental Research, 44(4), 856–865. https://doi.org/10.1111/acer.14299
Palma, E., Doornebal, E. J., & Chokshi, S. (2019). Precision-cut liver slices: a versatile tool to advance liver research. Hepatology International, 13(1), 51–57. https://doi.org/10.1007/s12072-018-9913-7
Palma, E., Ma, X., Riva, A., Iansante, V., Dhawan, A., Wang, S., Ni, H.-M., Sesaki, H., Williams, R., Ding, W.-X., & Chokshi, S. (2019). Dynamin-1-Like Protein Inhibition Drives Megamitochondria Formation as an Adaptive Response in Alcohol-Induced Hepatotoxicity. The American Journal of Pathology, 189(3), 580–589. https://doi.org/10.1016/j.ajpath.2018.11.008