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Can autoimmunity cause neurological problems?

Can autoimmunity cause neurological problems?

by Elise Wachspress

Celiac disease is a serious autoimmune disorder. When those with celiac eat gluten—a group of proteins found in cereal grains like wheat and barley—their immune systems respond by inflaming and damaging the little “fingers” of tissue that absorb food nutrients in the small intestine.

About one in every 100 Americans has celiac, but many don’t realize it. The disease can be hard to diagnose, because symptoms are so diffuse: anemia, osteoporosis, loss of dental enamel, heartburn, headaches, tingling hands, joint pain, a blistery skin rash, etc. Children may suffer vomiting, diarrhea, poor appetite, muscle wasting, and even failure to thrive; adolescents may be abnormally small for their age, with delayed puberty.

Among the hardest symptoms to pinpoint and link to celiac is what some patients call “brain fog.” Those with the disease often report episodes of headaches, depression, moodiness, difficulty concentrating, fumbling to choose words, and/or feeling tired even though they just got out of bed. Sometimes only when people are diagnosed with celiac, change to a gluten-free diet, and then find these symptoms disappear do they realize how celiac inflammation affected the clarity of their neural processing.

The problem is, total gluten elimination is hard to accomplish. While gluten-free foods and restaurants are becoming increasingly common, food is fundamental to most social relationships, and it’s hard to manage every interaction without seeming prickly or oversensitive.

And many “non-food” products use gluten as an edible “glue” to bind mixtures together, including some vitamins, medications, lipsticks and lip balms, even bouillon cubes. Then there are the products one might never suspect involve gluten, like pickles, hot cocoa mix (Celiac patients often make their own), and soy sauce (One can substitute the safer tamari).

So what happens when a patient with celiac has an inadvertent exposed to gluten? Or the pizza shows up in your child’s school and resistance is low? Some people find themselves living through several days when their brains just don’t seem to function. Work and school become a challenge, even for people who are normally bright and creative. People accidentally exposed to gluten report symptoms from irritability to anxiety to full-blown panic attacks.

Bana Jabri, MD, PhD, has long been interested in understanding the neurological distress that sometimes follows accidental gluten exposure. She wants to find out if immune factors called cytokines, released in response to gluten exposure, affect brain chemistry and the nerve centers feeding back to the gut. Understanding the relationship would provide a better understanding not only the neurological mechanisms involved in celiac disease, but also in other autoimmune conditions, like multiple sclerosis and rheumatoid arthritis, in which patients also report similarly diffuse cognitive impairment.

Jabri has established a collaboration with Jean Decety, PhD, a UChicago neuroscientist internationally recognized for his work in using fMRI (functional magnetic resonance imaging) to understand affective behavior. While a handful of case studies have used fMRI to study extremely serious neurological symptoms in individual patients with celiac disease, no one has yet undertaken a larger study of how celiac creates the “brain fog” that seems such a common complaint.

The plan is to have patients undergo fMRI, immunological, and other testing before and after a controlled gluten ingestion, to map the changes in all these factors. Jabri and Decety hope the results will help generate novel insights into the neurological impact of the disease and potential therapeutic avenues to prevent these negative outcomes.

Right now they are searching for funding to support these studies. But what they find may make life a lot easier for the three million Americans living with celiac disease, some living in fear that they may accidentally ingest something that will put them in a fog for days.

Elise Wachspress is a senior communications strategist for the University of Chicago Medicine & Biological Sciences Development office

 

Engineering the immune system to fight breast cancer

Engineering the immune system to fight breast cancer

by Paulette Krishack
Post-doctoral fellow in the University of Chicago’s Department of Medicine

Breast cancer is one of the most commonly diagnosed cancers in women. Approximately one in eight will develop the disease in their lifetime, and over 40,000 in the U.S. will die from it this year. While genetics plays a role, 85 percent of women diagnosed with breast cancer have no family history, and effective prevention and treatment depends on identifying the other factors involved.

Clinicians break down breast cancers into at least five types, based on the molecular features present in the tumor cell. Several types are known to show hormone “receptors” (most commonly estrogen, progesterone, and a protein called HER-2) which offer targets for treatment.

But in one type, triple negative breast cancer (TNBC), tumor cells lack the hormone receptors and HER-2 protein known to fuel breast cancer. Finding a way to specifically target TNBC, a particularly aggressive form of cancer, is critical.

Obesity is known as a risk factor for breast cancer incidence and progression. Because obesity can cause chronic, systemic inflammation, Lev Becker, PhD, Marsha Rosner, PhD, and Payal Tiwari, PhD, were interested in finding out how the immune system might be involved in TNBC.

Becker has dedicated his laboratory and career to studying macrophages, the “big eaters” of the immune system, while Rosner specializes in cancer therapeutics. Although macrophages are powerful fighters of viruses and bacteria, they can also be called in to engulf the saturated fatty acids found in many high-fat foods, causing high-fat induced inflammation in the tissues they invade. Becker, Rosner, and Tiwari wanted to see if these obesity-associated macrophages were involved in TNBC.

Using a mouse model of TNBC, they found that the most common macrophages in the breast fat tissue of obese mice were a type specifically activated by a high-fat diet. These macrophages produced a pro-inflammatory protein, a cytokine called IL-6, which created a nurturing environment for TNBC tumors to grow. The team also found that switching the obese mice to a low-fat diet slowed tumor development. Studies also showed human tumor tissue with similar results: there were fewer macrophages present in tissues from lean patients than obese ones.

These studies suggest that immunotherapy—treatments targeting the immune response that is activated by macrophages—may offer innovative care for patients with TNBC, especially if they are obese. They may also offer potential strategies for treating other diseases linked to obesity, particularly those that involve macrophages, such as cardiovascular disease.

Most importantly, this research demonstrates the value of diet in maintaining health. A third of American adults are obese and another third overweight. Now that we know the toll a high-fat diet exerts on molecules in our body, we can embrace the mission of the Duchossois Family Institute: Use the knowledge we develop to improve our health and all those with whom we share the planet.

 

News roundup: August/September 2019

News roundup: August/September 2019

A selection of health news from the University of Chicago and around the globe curated just for you.

Will these startups help biotech take root in Chicago?
Tom Gajewski is stepping into the spotlight with Pyxis Oncology, a cancer-therapy startup. He and co-founders John Flavin and David Steinberg raised $22 million to launch the spinout from his lab. (Crain’s Chicago Business)

Can gut bacteria heal food allergies?
How manipulating the microbiome could reverse and prevent peanut allergies and more. Cathryn Nagler featured. (Elemental by Medium)

Study finds an unexpected link between farming and immune system evolution
A new study by University of Chicago Medicine genetic researcher Luis Barreiro found the immune systems of hunter-gatherers showed more signs of positive natural selection, in particular among genes involved in the response to viruses. (phys.org)

Wash U team finds the ‘signature’ of guts that don’t get c. diff
Researchers have found the molecular signature of a healthy gut microbiome—the kind of bacterial community that keeps Clostridium difficilein check even in the aftermath of antibiotic treatment. (Futurity)

With new grants, Gates Foundation takes an early step toward a universal flu vaccine
Scientific teams from inside and outside the world of influenza research have been awarded funding to try to unlock mysteries that could provide the foundation for a future universal flu vaccine. Patrick Wilson featured. (STAT)

Human breast milk may help babies tell time via circadian signals from mom
The composition of breast milk changes across the day. Researchers believe this “chrononutrition” may help program infants’ emerging circadian biology. (The Conversation)

Just four nights with less sleep can alter fat storage
Restricting sleep for just four days alters how the body metabolizes fats and changes how satisfying meals seem, according to a new study with 15 healthy men. (Futurity)

 

Building a research foundation to optimize health at the Duchossois Family Institute

Building a research foundation to optimize health at the Duchossois Family Institute

In 2017, the University of Chicago Medicine established the Duchossois Family Institute: Harnessing the Microbiome and Immunity for Human Health (DFI). The institute is dedicated to developing new knowledge about human biological defense systems, including the microbiome, and their potential for preventing disease and maintaining lifelong wellness.

After a national search, renowned physician-scientist Eric G. Pamer, MD, was recruited to become DFI’s inaugural director in July 2019. Formerly with Memorial Sloan Kettering Cancer Center, Pamer is tasked with building the DFI’s research capabilities, from recruiting new faculty and building core facilities to translating discoveries into treatments that can be used in the clinic. UChicago Medicine spoke to him about his plans, and what he hopes to see the DFI accomplish.

Read the full Q&A on “The Forefront” >>

 

Check out the Checkpoints and their answer to cancer

Check out the Checkpoints and their answer to cancer

by Elise Wachspress

In the world of cancer research, Thomas Gajewski, MD, PhD, is a rock star. And not just because he plays lead guitar for The Checkpoints, an all-cancer-researcher band that includes his longtime colleague Jim Allison, last year’s Nobel Prize winner for physiology or medicine (and professor at the MD Anderson Cancer Center) on harmonica.

Named a Giant of Cancer Care in 2017, Gajewski has, for more than two decades, worked in cancer immunotherapy, a field only recently recognized as the most promising for actual cancer cures—a word that makes most clinicians nervously back away.

Gajewski has dedicated his career to figuring out how to help patients’ immune systems fight cancer from within. Much of his work has focused on checkpoint inhibitors, proteins which our bodies use to keep immune responses in check, so we don’t attack beneficial bacteria or our own cells. But checkpoint inhibitors can also keep our immune system from killing cancer cells (and thus the name chosen for Gajewski’s band).

Over the past century, the idea of fighting cancers with immunotherapies has fallen in and out of favor multiple times. But oncologists are now watching the field—and Gajewski’s work—with excitement. Recent research shows that, in metastatic melanoma and many other solid cancers, immunotherapies cause tumors to regress or even disappear in 30-50% of patients. These treatments are often significantly less toxic than surgery, radiation, or traditional chemotherapy. And by training the body to recognize and kill cancer cells, immunotherapies offer an opportunity for truly durable results, offering patients a chance at living long, healthy, cancer-free lives.

But Gajewski, the AbbVie Foundation Professor of Cancer Immunotherapy, is focused past these success stories. What drives his curiosity and his passion is understanding why immunotherapies fail. And one of his most remarkable findings is that the bacteria patients carry in their guts—their microbiome—can strongly influence whether or not cancer immunotherapy works.

As with most scientific breakthroughs, this one came through a combination of dogged dedication, careful observation, and wonder. When Gajewski and his team implanted mice with melanoma tumors, they noticed immunotherapy response differed depending upon the commercial source of the animals themselves; one supplier’s mice fared much better, even though they were identical strains. The team finally found that the mice were delivered to the lab carrying a certain type of gut bacteria responded much better to the therapy.

Even more tantalizing: when the two sets of mice were housed together, outcomes improved for the mice from the other supplier. Sharing these healthy gut bacteria was key to therapeutic success.

Gajewski and team are now working to identify bacteria found in humans that can produce these effects in mice. The team will use a system in which germ-free mice are colonized with microbial material from patients, implanted with tumors, and then treated with immunotherapy drugs. The goal is to figure out the exact mechanism of how bacteria promote or restrict anti-tumor immunity—knowledge that will provide a foundation for new therapeutics. By developing computational algorithms which integrate genomic sequencing of the microbiota, the tumor oncogenes, and germline polymorphisms, they aim to get a comprehensive view of immunotherapy success versus resistance in each individual patient.

The goal is a diagnostic approach that will help clinicians—like Gajewski himself—decide the most effective way to use immunotherapy for each patient and tumor, perhaps by simply introducing new types of bacteria to a patient’s gut. While we commonly think of probiotics as a way to improve digestion or alleviate allergies, we may one day find an avenue to use much more sophisticated, designer probiotics to treat some cancers.

Gajewski recently received a promise of nearly half a million dollars from the Melanoma Research Alliance to advance this research. However, securing this award requires him to match the grant with similar funding from other sources.

For anyone ready to invest in much more effective, less debilitating treatments—perhaps even cures—for cancer, Gajewski has a strategy ready for prime time, a track record of unusual research success, and a group of musicians ready to sing about it.

Elise Wachspress is a senior communications strategist for the University of Chicago Medicine & Biological Sciences Development office

 

News roundup: March 2019

News roundup: March 2019

A selection of health news from the University of Chicago and around the globe curated just for you.

Polsky Center’s Life Science Launchpad partners with faculty to launch startups
The Launchpad bridges the gap between academic research and entrepreneurship by forming hands-on partnerships with life sciences researchers who seek to convert their research products into business ventures. Cathryn Nagler and Eugene Chang featured. (Polsky Center for Entrepreneurship and Innovation)

How the microbiome could be the key to new cancer treatments
The effectiveness of drugs that help the immune system fight cancer cells appears to depend on bacteria in the gut. (Smithsonian magazine)

Training cells to attack
Groundbreaking CAR T-cell therapy engineers cells to target tumors. Michael Bishop featured. (Chicago Health)

How to reduce the chances of being hospitalized for Crohn’s disease
Take these steps to lessen the risk of complications from the inflammatory bowel disease. David Rubin featured. (U.S. News and World Report)

Real innovation is going to be centered on how we collect, standardize, and harmonize data
Bridging the gap between clinical care and research means creating two-way collaboration, and improving the way in which data is collected, organized, shared. Sam Volchenboum featured. (Outsourcing-Pharma.com)