Emeritus ProfessorNigel Gooderham
Emeritus Professor of Molecular Toxicology
Department of Metabolism, Digestion and Reproduction - Faculty of Medicine
Orcid identifier0000-0001-7645-8219 (opens in a new tab)
- Emeritus Professor of Molecular ToxicologyDepartment of Metabolism, Digestion and Reproduction - Faculty of Medicine
- Burlington Danes, Hammersmith Campus, United Kingdom
RESEARCH
Nigel’s research interests include:
Mechanisms of chemical carcinogenesis
Mechanisms of genotoxicity and mutation
Molecular, cellular and genomic responses to toxicity
Role of miRNA in chemical carcinogenesis and toxicity
The genetic toxicology of food-derived chemicals and oligonucleotides
Our research attempts to understand and evaluate the hazard and risk to man of carcinogenic chemicals, especially food-borne molecules. The consumption of cooked meat, particularly when well done, is associated with a high incidence of colon, prostate, mammary and other cancers. One group of chemicals that have proved to be of particular interest are the food-derived heterocyclic amines that are formed during the cooking of food; these heterocyclic amines (Has) are metabolically activated to highly potent DNA damaging derivatives. Indeed, if these compounds were present in our environment as man-made contaminants, their toxicity would almost certainly have prompted regulatory legislation. Our programme explores exposure, bioavailablity, disposition, metabolism, activation and genotoxicity of the HAs in man using chemical, analytical and molecular technologies.
About 20 genotoxic HAs have been shown to be formed at the parts per billion level during the normal cooking of food. Two of the most abundant HAs are 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Both compounds are highly DNA damaging and carcinogenic in rodent bioassays inducing tumours in a variety of tissues, including, in the case of PhIP, the colon, prostate and mammary glands.
Our interest in DNA damage and mutation is underpinned by mechanistic research in a variety of in vitro models, using cell culture, molecular biology and biochemistry as well as high end analytical approaches such as metabonomics. Our programme explores not only small molecular weight chemicals but also oligonucleotide toxicity and genotoxicity and oligonucleotide mediated change in cell biology and phenotypic expression.
The consequence of chemical-induced toxicity can be acute phenotypic change or inheritable genetic change or cell death. Understanding the mechanisms whereby these phenotypic responses occur is important for recognising the toxicity of the molecules involved and for understanding the cellular responses to toxicity and identifying biomarkers of toxicity. A major focus is to investigate the role of miRNAs in toxicity. These small (22 nucleotide length non coding RNAs) are post-transcriptional regulators of gene expression. Numerous studies have shown that these miRNAs are strongly associated with important biological processes such as development, homeostasis and pathology, including cancer. We believe that miRNAs are key mediators of both acute toxicity and more chronic events such as those associated with carcinogenesis. As such we are investigating the potential of miRNAs as biomarkers of toxicity and disease and understanding gene expression changes and dysregulation of miRNAs also offers clues to the mechanisms operating in toxicity and pathology.
Active areas of research include the role of miRNAs in genotoxic and epigenetic chemical carcinogenesis, the role of miRNAs in hormonal disturbances, surgery-related pathology, metabolic surgery, obesity and nephropathy. Much of this work is translational, bridging in vitro based models with clinical research.
We also have active research in the area of inflammation and drug metabolism as it relates to toxicity and cancer. We have a focus on the colonic tumour microenvironment, which comprises epithelial and stromal cell populations that can manipulate the phenotypic expression of tumour tissue, compared to normal tissue, via cell to cell communication. We have found that important contributors to this crosstalk include inflammatory cytokines and more recently the role of microRNAs has emerged. These key players metabolically empower colon cancer cells, mediate intracellular communication and offer therapeutic opportunities to target the cancer microenvironment. A recent interest has emerged that looks at the role of chromatin architecture in chemical-mediated genetic toxicology.
Mechanisms of chemical carcinogenesis
Mechanisms of genotoxicity and mutation
Molecular, cellular and genomic responses to toxicity
Role of miRNA in chemical carcinogenesis and toxicity
The genetic toxicology of food-derived chemicals and oligonucleotides
Our research attempts to understand and evaluate the hazard and risk to man of carcinogenic chemicals, especially food-borne molecules. The consumption of cooked meat, particularly when well done, is associated with a high incidence of colon, prostate, mammary and other cancers. One group of chemicals that have proved to be of particular interest are the food-derived heterocyclic amines that are formed during the cooking of food; these heterocyclic amines (Has) are metabolically activated to highly potent DNA damaging derivatives. Indeed, if these compounds were present in our environment as man-made contaminants, their toxicity would almost certainly have prompted regulatory legislation. Our programme explores exposure, bioavailablity, disposition, metabolism, activation and genotoxicity of the HAs in man using chemical, analytical and molecular technologies.
About 20 genotoxic HAs have been shown to be formed at the parts per billion level during the normal cooking of food. Two of the most abundant HAs are 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Both compounds are highly DNA damaging and carcinogenic in rodent bioassays inducing tumours in a variety of tissues, including, in the case of PhIP, the colon, prostate and mammary glands.
Our interest in DNA damage and mutation is underpinned by mechanistic research in a variety of in vitro models, using cell culture, molecular biology and biochemistry as well as high end analytical approaches such as metabonomics. Our programme explores not only small molecular weight chemicals but also oligonucleotide toxicity and genotoxicity and oligonucleotide mediated change in cell biology and phenotypic expression.
The consequence of chemical-induced toxicity can be acute phenotypic change or inheritable genetic change or cell death. Understanding the mechanisms whereby these phenotypic responses occur is important for recognising the toxicity of the molecules involved and for understanding the cellular responses to toxicity and identifying biomarkers of toxicity. A major focus is to investigate the role of miRNAs in toxicity. These small (22 nucleotide length non coding RNAs) are post-transcriptional regulators of gene expression. Numerous studies have shown that these miRNAs are strongly associated with important biological processes such as development, homeostasis and pathology, including cancer. We believe that miRNAs are key mediators of both acute toxicity and more chronic events such as those associated with carcinogenesis. As such we are investigating the potential of miRNAs as biomarkers of toxicity and disease and understanding gene expression changes and dysregulation of miRNAs also offers clues to the mechanisms operating in toxicity and pathology.
Active areas of research include the role of miRNAs in genotoxic and epigenetic chemical carcinogenesis, the role of miRNAs in hormonal disturbances, surgery-related pathology, metabolic surgery, obesity and nephropathy. Much of this work is translational, bridging in vitro based models with clinical research.
We also have active research in the area of inflammation and drug metabolism as it relates to toxicity and cancer. We have a focus on the colonic tumour microenvironment, which comprises epithelial and stromal cell populations that can manipulate the phenotypic expression of tumour tissue, compared to normal tissue, via cell to cell communication. We have found that important contributors to this crosstalk include inflammatory cytokines and more recently the role of microRNAs has emerged. These key players metabolically empower colon cancer cells, mediate intracellular communication and offer therapeutic opportunities to target the cancer microenvironment. A recent interest has emerged that looks at the role of chromatin architecture in chemical-mediated genetic toxicology.