Prying into the Origins of Disease, Experts Gather at YSPH for Scientific Imaging Symposium

Many of tomorrow’s biggest health advances will depend on the tiniest bits of evidence today.

To explore the latest trends, obstacles and successes in the biosciences, where success hangs on seeing things a few microns (or smaller) in size, the Department of Environmental Health Sciences at the Yale School of Public Health hosted a daylong symposium (November 22) on mass spectrometry that drew experts from industry and academia to compare how they are using imaging technology to pry ever deeper into the mysteries of biology—and disease.

“This is an incredible opportunity for top scientists to learn from one another. I am thrilled to have the Yale School of Public Health host this event for the second time in the last three years,” said Vasilis Vasiliou, Ph.D., Susan Dwight Bliss Professor of Epidemiology, department chair and an organizer of the event. The symposium was sponsored by Waters Corp., a Massachusetts-based company that manufactures a range of scientific software and instruments, including mass spectrometers.

Vasiliou introduced Richard Caprioli, Ph.D., a professor at Vanderbilt University, as the father of modern scientific imaging. Caprioli described how his lab is in the process of creating 3-D, ultra-high-resolution digital models of human organs, including the kidney. The process is painstaking, but it could have profound implications for better understanding and solving a range of diseases, including cancers.

In the molecular age, scientists need better means to analyze the onset and spread of disease. Mass spectrometry offers this.

“There’s much, much more to be learned,” Caprioli told the gathering in Winslow Auditorium.

Other speakers outlined how they are using mass spectrometry, commonly referred to as MS or mass spec, to study drug distribution in the body and how effective it is in fighting tumors, the use of mammalian reagents and alcoholic liver disease.

The Department of Environmental Health Sciences at the Yale School of Public Health is using mass spectrometry to qualitatively and quantitatively measure low molecular weight chemicals (metabolites) in biological matrices, said Caroline Johnson, Ph.D., an assistant professor at the school and a presenter at the symposium.

Understanding metabolites is important for public health as it informs researchers about an individual’s internal biochemistry and how they respond to both external stressors such as environmental exposures and dietary change) and internal stressors (disease). Obtaining a systems-level view of metabolites allows for detailed knowledge of biological changes at the metabolic pathway/network level and thus any associated gene- or protein-level aberrations.

“This state-of-the-art technology can also reveal biomarkers of exposure and disease, and thus provide targets for potential therapeutic intervention,” Vasiliou said. “We are also using imaging mass spectrometry to assess the spatial specificity of metabolites within tissues. Using this information, it is possible to identify metabolites that are associated with cell type, pathology and drug distribution.”

Vasiliou’s lab is using MS-based untargeted metabolomics and imaging MS to identify changes in lipids and other small molecules that are associated with alcohol abuse and alcoholic liver disease (ALD). Alcohol abuse is a significant global problem and is ranked as one of the top five risk factors for death and disability globally.

The lab is using lipidomis and metabolomic analyses to identify biomarkers before pathological changes can be detected by traditional diagnostic methods. This finding is potentially groundbreaking if patients with ALD can be diagnosed at an early stage, allowing the disease to be reversed through abstinence. Vasiliou is also using imaging MS to spatially identify metabolite changes in the livers of people with ALD, which could provide novel mechanistic details on the development of ALD. He intends to use imaging MS along with Artificial Intelligence and deep-learning in collaboration with Kirill Veselkov (Imperial College London) to generate 3-D ultra-high-resolution digital models of healthy and diseased liver.

Johnson’s lab focuses on understanding sex-differences in colorectal cancer metabolism. Colorectal cancer has the highest incidence in men, but further examination of incidence by lesion location show that women have a higher incidence of right-sided colon cancer. This is of concern as patients with right-sided colon cancer have the highest mortality of all colorectal cancer cases.

Carrying out untargeted metabolomics on tumor tissues from more than 200 patients, Johnson’s lab discovered that women with right-sided colon cancer have a specific metabolic phenotype that indicates nutrient depletion, an upregulation of asparagine synthesis and association with mutations. She is currently investigating these links in various models, to determine whether asparagine metabolism could be a potential therapeutic target for these individuals.

“This symposium highlights how MS is being used in both industry and academia, and the most recent advances in the field,” said Johnson. “It is inspiring to see what can be done with these technologies and what is possible for public health,” Vasiliou added.