The Viruses Within Us: Dr. Caleb Lareau Awarded Michelson Prize to Study How the Human ‘Virome’ Influences Health

The human body is teeming with viruses – some 380 million of them – and Dr. Caleb Lareau wants to meet them all.

“There are ten times more viruses than there are human cells, so in some measure, you are more virus than you are human,” he says. “They have to be doing something in terms of impacting our health.”

The Michelson Medical Research Foundation and the Human Immunome Project have awarded Lareau one of the 2024 Michelson Prizes: Next Generation Grants in recognition of his proposal to characterize how viruses in the human body influence the immune system and diseases such as cancer.

Lareau, a computational and systems biologist at Memorial Sloan Kettering Cancer Center, was drawn to viruses because of their sheer ubiquity. Some live in places like the gut, while others are embedded in the human genome. The latter type mostly lies dormant and has been largely dismissed as “junk DNA” in genome sequencing efforts.

But much like the microbiome, the collection of bacteria that live in each person, the “virome” could have an impact on human health – everything from inflammatory bowel disease to mental disorders. Lareau is combing through genetic sequences in search of known viruses and hidden ones that can be stitched together through computational approaches. “We have viruses just sitting there in DNA sequencing sets, and those pieces haven't been put together,” he says. Ultimately, he hopes to discover how a person’s environment and lifestyle may influence the viruses that make up their individual virome and how those viruses affect the body. 

Lareau has the perfect background for such exploratory research. As an undergraduate at the University of Tulsa and PhD student at Harvard University, he developed mathematical methods to study how genes are expressed across the human genome and within individual cells. Later, as a postdoc at Stanford University, he studied immune cells that could be harnessed to kill cancer. “It was just so exciting to be able to test thousands of hypotheses in parallel effectively by running computational and statistical models on large data sets,” he says. 

The Michelson Prizes grants, $150,000 grants awarded annually to investigators 35 or younger who are focused on human immunology, vaccine discovery, and immunotherapy, will allow Lareau to continue combing through DNA datasets without any particular hypotheses in mind and chasing down interesting viruses wherever he finds them. 

It’s a risky approach for a brand-new lab like Lareau’s. “Several projects may go up in smoke, and not everyone can kind of tolerate that kind of risk,” he says. “It’s extremely galvanizing to get an award like this early in my career because it signals that what we're doing, though unconventional, is serious and could have an impact.”

However, his work has already shown that it may make a clinical impact. In one study, he looked at how viruses can affect chimeric antigen receptor (CAR) T cells – a highly effective cancer therapy in which immune cells are removed from a person’s body, engineered with a protein that allows them to better recognize cancer cells and reinfused into the patient. 

Lareau found that the process of making CAR-T cells infrequently can activate a herpesvirus known as HHV-6. While HHV-6 is present in nearly everyone’s T cells, it can cause deadly encephalitis in immune-compromised people, such as cancer patients - including some who took part in clinical trials of CAR-T cells. Lareau’s work indicated that removing the cells from their native environment in the body may free them from the immune system that normally keeps HHV-6 in check.

Cancer isn’t the only disease in which viruses might play an unexpected role. Some evidence suggests that infections may contribute to Alzheimer's disease in some people – a provocative idea, Lareau says, because it may suggest that people could be vaccinated against the disease. 

Lareau is also interested in a recently discovered virus family called anelloviruses, which are prevalent in immune cells but don’t seem to cause any immune reaction. If the human immune system doesn’t notice these viruses, he says, they may one day prove to be good vectors to carry gene therapies into the body without triggering an immune reaction. On the other hand, recent evidence suggests that viruses may trigger autoimmune diseases if activated – yet another potential line of research for Lareau to explore. “We'll just have to go where the data takes us,” he says.