Caroline Helen Johnson, PhD

Sex-related differences in colorectal cancer

In 2020, we published the first sex-stratified metabolomics analysis of tumor tissues from colorectal cancer patients https://pubmed.ncbi.nlm.nih.gov/32184446/. We observed that tumors from female patients used different energy and macromolecule generating pathways compared to tumors from male patients. We also showed that aberrant asparagine metabolism is a hallmark of tumors from female patients only, and associates with poorer clinical outcomes for these patients https://pubmed.ncbi.nlm.nih.gov/35208238/. Since the publication of this work, a major research focus in the lab is to understand this association between asparagine and sex-differences in colorectal cancer biology and outcomes. https://pubmed.ncbi.nlm.nih.gov/38886847/, https://pubmed.ncbi.nlm.nih.gov/39039782/, https://pubmed.ncbi.nlm.nih.gov/40228761/.

Early-onset colorectal cancer metabolism

There is a growing incidence in colorectal cancers occurring in individuals aged under 50 years old. The etiology and mechanisms of which are not well understood. We recently performed the first metabolomics analysis of tumors from individuals aged under 50 and compared the metabolic profiles to those from those aged 50 and over. We found that younger patients had downregulated dopamine metabolism and increased phospholipid metabolism. We are now performing studies to validate these findings. https://pubmed.ncbi.nlm.nih.gov/40865779/

Identifying the biological effects of exposures

In the Johnson Lab, we use metabolomics to simultaneously analyze both exogenous chemicals, their metabolites, and changes to the endogenous metabolome to allow assessment of exposures and their biological impact. We also adjust for confounding using epidemiologic techniques, as shared factors could influence the metabolome and exposure measured.

Dried blood spots are a window to early-life exposures that contribute to later-life cancers

Early-life exposures can have biological effects that lead to later-life adverse outcomes such as cancer. Dried blood spots (DBS) have been collected in large populations for decades, to screen infants for congenital metabolic disorders, however they represent an untapped resource for studies in epidemiology and population sciences. Metabolomics analysis of DBS from newborns provides the opportunity to measure both environmental exposures and metabolic perturbations simultaneously, offering both biomarkers of exposure and biological effect to gain insight into mechanisms of later life diseases. No consensus exists for the optimal method for metabolite normalization in DBS untargeted LC-MS-based metabolomics. To address this issue and setup a robust experimental protocol for DBS metabolomics, we assessed the performance of various normalization methods. We identified that normalization using hemoglobin (Hb) is the best method. We also introduced a novel role of specific gravity as a predictor of Hb in DBS. https://pubmed.ncbi.nlm.nih.gov/36113793/