Skip to main content

taste

All of Us: Partnering Together for the Future of Precision Medicine

Posted on by

All of Us Research Program
Credit: All of Us Research Program

Over the past year, it’s been so inspiring to watch tens of thousands of people across the country selflessly step forward for vaccine trials and other research studies to combat COVID-19. And they are not alone. Many generous folks are volunteering to take part in other types of NIH-funded research that will improve health all across the spectrum, including the more than 360,000 who’ve already enrolled in the pioneering All of Us Research Program.

Now in its second year, All of Us is building a research community of 1 million participant partners to help us learn more about how genetics, environment, and lifestyle interact to influence disease and affect health. So far, more than 80 percent of participants who have completed all the initial enrollment steps are Black, Latino, rural, or from other communities historically underrepresented in biomedical research.

This community will build a diverse foundation for precision medicine, in which care is tailored to the individual, not the average patient as is now often the case. What’s also paradigm shifting about All of Us is its core value of sharing information back with participants about themselves. It is all done responsibly through each participant’s personal All of Us online account and with an emphasis on protecting privacy.

All of Us participants share their health information in many ways, such as taking part in surveys, offering access to their electronic health records, and providing biosamples (blood, urine, and/or saliva). In fact, researchers recently began genotyping and sequencing the DNA in some of those biosamples, and then returning results from analyses to participants who’ve indicated they’d like to receive such information. This first phase of genotyping DNA analysis will provide insights into their genetic ancestry and four traits, including bitter taste perception and tolerance for lactose.

Results of a second sequencing phase of DNA analysis will likely be ready in the coming year. These personalized reports will give interested participants information about how their bodies are likely to react to certain medications and about whether they face an increased risk of developing certain health conditions, such as some types of cancer or heart disease. To help participants better understand the results, they can make a phone appointment with a genetic counselor who is affiliated with the program.

This week, I had the pleasure of delivering the keynote address at the All of Us Virtual Face-to-Face. This lively meeting was attended by a consortium of more than 2,000 All of Us senior staff, program leads with participating healthcare provider organizations and federally qualified health centers, All of Us-supported researchers, community partners, and the all-important participant ambassadors.

If you are interested in becoming part of the All of Us community, I welcome you—there’s plenty of time to get involved! To learn more, just go to Join All of Us.

Links:

All of Us Research Program (NIH)

Join All of Us (NIH)


These Oddball Cells May Explain How Influenza Leads to Asthma

Posted on by

Cells of a mouse lung after an H1N1 infection
Credit: Andrew Vaughan, University of Pennsylvania, Philadelphia

Most people who get the flu bounce right back in a week or two. But, for others, the respiratory infection is the beginning of lasting asthma-like symptoms. Though I had a flu shot, I had a pretty bad respiratory illness last fall, and since that time I’ve had exercise-induced asthma that has occasionally required an inhaler for treatment. What’s going on? An NIH-funded team now has evidence from mouse studies that such long-term consequences stem in part from a surprising source: previously unknown lung cells closely resembling those found in taste buds.

The image above shows the lungs of a mouse after a severe case of H1N1 influenza infection, a common type of seasonal flu. Notice the oddball cells (green) known as solitary chemosensory cells (SCCs). Those little-known cells display the very same chemical-sensing surface proteins found on the tongue, where they allow us to sense bitterness. What makes these images so interesting is, prior to infection, the healthy mouse lungs had no SCCs.

SCCs, sometimes called “tuft cells” or “brush cells” or “type II taste receptor cells”, were first described in the 1920s when a scientist noticed unusual looking cells in the intestinal lining [1] Over the years, such cells turned up in the epithelial linings of many parts of the body, including the pancreas, gallbladder, and nasal passages. Only much more recently did scientists realize that those cells were all essentially the same cell type. Owing to their sensory abilities, these epithelial cells act as a kind of lookout for signs of infection or injury.

This latest work on SCCs, published recently in the American Journal of Physiology–Lung Cellular and Molecular Physiology, adds to this understanding. It comes from a research team led by Andrew Vaughan, University of Pennsylvania School of Veterinary Medicine, Philadelphia [2].

As a post-doc, Vaughan and colleagues had discovered a new class of cells, called lineage-negative epithelial progenitors, that are involved in abnormal remodeling and regrowth of lung tissue after a serious respiratory infection [3]. Upon closer inspection, they noticed that the remodeling of lung tissue post-infection often was accompanied by sustained inflammation. What they didn’t know was why.

The team, including Noam Cohen of Penn’s Perelman School of Medicine and De’Broski Herbert, also of Penn Vet, noticed signs of an inflammatory immune response several weeks after an influenza infection. Such a response in other parts of the body is often associated with allergies and asthma. All were known to involve SCCs, and this begged the question: were SCCs also present in the lungs?

Further work showed not only were SCCs present in the lungs post-infection, they were interspersed across the tissue lining. When the researchers exposed the animals’ lungs to bitter compounds, the activated SCCs multiplied and triggered acute inflammation.

Vaughan’s team also found out something pretty cool. The SCCs arise from the very same lineage of epithelial progenitor cells that Vaughan had discovered as a post-doc. These progenitor cells produce cells involved in remodeling and repair of lung tissue after a serious lung infection.

Of course, mice aren’t people. The researchers now plan to look in human lung samples to confirm the presence of these cells following respiratory infections.

If confirmed, the new findings might help to explain why kids who acquire severe respiratory infections early in life are at greater risk of developing asthma. They suggest that treatments designed to control these SCCs might help to treat or perhaps even prevent lifelong respiratory problems. The hope is that ultimately it will help to keep more people breathing easier after a severe bout with the flu.

References:

[1] Closing in on a century-old mystery, scientists are figuring out what the body’s ‘tuft cells’ do. Leslie M. Science. 2019 Mar 28.

[2] Development of solitary chemosensory cells in the distal lung after severe influenza injury. Rane CK, Jackson SR, Pastore CF, Zhao G, Weiner AI, Patel NN, Herbert DR, Cohen NA, Vaughan AE. Am J Physiol Lung Cell Mol Physiol. 2019 Mar 25.

[3] Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury. Vaughan AE, Brumwell AN, Xi Y, Gotts JE, Brownfield DG, Treutlein B, Tan K, Tan V, Liu FC, Looney MR, Matthay MA, Rock JR, Chapman HA. Nature. 2015 Jan 29;517(7536):621-625.

Links:

Asthma (National Heart, Lung, and Blood Institute/NIH)

Influenza (National Institute of Allergy and Infectious Diseases/NIH)

Vaughan Lab (University of Pennsylvania, Philadelphia)

Cohen Lab (University of Pennsylvania, Philadelphia)

Herbert Lab (University of Pennsylvania, Philadelphia)

NIH Support: National Heart, Lung, and Blood Institute; National Institute on Deafness and Other Communication Disorders