DrValentina Caputo
Honorary Research Fellow
Department of Immunology and Inflammation - Faculty of Medicine
- Honorary Research FellowDepartment of Immunology and Inflammation - Faculty of Medicine
- Commonwealth Building, Hammersmith Campus, United Kingdom
BIO
Research Interest
Epigenetic mechanisms in human disease and the development of epigenetic therapeutic approaches.
My particular interest is in investigating the molecular mechanisms by which nuclear architecture, transcriptional regulation and epigenetics can be causative of a disease phenotype and how this can be targeted for therapy of human disorders.
Projects:
1. Epigenetic control of house-keeping genes by Sp1 and histone acetylation: molecular mechanisms and therapeutic potential.
Transcription factor binding and chromatin accessibility seen as histone acetylated regions on the promoter are the prerequisite for active transcription.
We are interested in understanding the function that HDAC inhibitors play in the reversible de-repressive epigenetic state and as a result, the reversion of the phenotype. Understanding the HDAC inhibitors molecular mechanisms of action can open the possibility for using them in a broader type of diseases, and not only when there is deregulation of gene expression.
2. The impact of a disease-causing mutation/chromosomal translocation on the genomic interactome and its role on the disease phenotype.
We speculate that genes are not transcribed linearly and in isolation but instead can be part of more complex, multi-gene transcriptional units where enhancers play a crucial cell-lineage specific role. This would require the active genes/enhancers to loop out of their chromosomal territories forming supranuclear domains that are non random and can have a regulatory role.
3. Potent in vitro and in vivo anti-myeloma activity of BET inhibitors
BET inhibitors have shown significant anti-tumour and anti-inflammatory activity assessed in preclinical models of leukaemia, sepsis and autoimmune disease. We set to study the in vitro and in vivo activity of the I-BET compounds against multiple myeloma, and explore its molecular mechanism of action.
4. Effect of I-BET compounds on osteoclast activation and bone disease in multiple myeloma
Based on these anti-myeloma effect of I-BET, we predict that I-BET will have a significant inhibitory effect on osteoclast differentiation and in particular activation. We propose to conduct a preliminary study to investigate the effect of I-BET on basal bone homeostasis as well as on myeloma-related bone disease.
5. Role of transcription factors and chromatin regulators in myeloma survival and proliferation
Epigenetic mechanisms in human disease and the development of epigenetic therapeutic approaches.
My particular interest is in investigating the molecular mechanisms by which nuclear architecture, transcriptional regulation and epigenetics can be causative of a disease phenotype and how this can be targeted for therapy of human disorders.
Projects:
1. Epigenetic control of house-keeping genes by Sp1 and histone acetylation: molecular mechanisms and therapeutic potential.
Transcription factor binding and chromatin accessibility seen as histone acetylated regions on the promoter are the prerequisite for active transcription.
We are interested in understanding the function that HDAC inhibitors play in the reversible de-repressive epigenetic state and as a result, the reversion of the phenotype. Understanding the HDAC inhibitors molecular mechanisms of action can open the possibility for using them in a broader type of diseases, and not only when there is deregulation of gene expression.
2. The impact of a disease-causing mutation/chromosomal translocation on the genomic interactome and its role on the disease phenotype.
We speculate that genes are not transcribed linearly and in isolation but instead can be part of more complex, multi-gene transcriptional units where enhancers play a crucial cell-lineage specific role. This would require the active genes/enhancers to loop out of their chromosomal territories forming supranuclear domains that are non random and can have a regulatory role.
3. Potent in vitro and in vivo anti-myeloma activity of BET inhibitors
BET inhibitors have shown significant anti-tumour and anti-inflammatory activity assessed in preclinical models of leukaemia, sepsis and autoimmune disease. We set to study the in vitro and in vivo activity of the I-BET compounds against multiple myeloma, and explore its molecular mechanism of action.
4. Effect of I-BET compounds on osteoclast activation and bone disease in multiple myeloma
Based on these anti-myeloma effect of I-BET, we predict that I-BET will have a significant inhibitory effect on osteoclast differentiation and in particular activation. We propose to conduct a preliminary study to investigate the effect of I-BET on basal bone homeostasis as well as on myeloma-related bone disease.
5. Role of transcription factors and chromatin regulators in myeloma survival and proliferation
LANGUAGES
- Spanish; CastilianCan read, write, speak, understand and peer review
- ItalianCan read, write, speak, understand and peer review
- EnglishCan read, write, speak, understand and peer review
FACULTY
- Faculty of Medicine
POSITION NAME
- Honorary Research Fellow