Notre Dame News | Notre Dame News | News

’Tis the season for ticks and mosquitoes. A medical entomologist talks about these pests and how to avoid them.

2025-05-05T12:21:00-04:00

Lee R. Haines, associate research professor of biological sciences at Notre Dame.

As the weather warms and people begin to spend more time outside, ticks and mosquitoes will do the same. While these pests are annoying, even more than that, they can be a threat to our health.

As a medical entomologist, Associate Research Professor Lee R. Haines studies how insects spread diseases. Her research at the University of Notre Dame focuses specifically on the complex relationships between insects, the microorganisms living in their bodies, and the disease-causing agents they transmit to humans and animals

In five questions, Haines explains the risks mosquitoes and ticks pose to the Midwest and discusses how the public can best protect themselves and family members from these bloodthirsty pests.

When can people expect to see ticks and mosquitoes outside?

Ticks are hardier than mosquitoes so they are out now, and have been since it warmed up in February. The last one I removed (from myself) was in mid-November. In this part of the world, it would appear that we are at risk all year from ticks; if the ground warms up to 40-45 degrees, they become active.

Bloodthirsty female mosquitoes need it to be much warmer to start hunting us — they love the heat as much as most people do. In colder weather (below 60 degrees), mosquitoes cannot fly well, so the cool temperatures are a natural mosquito repellent. Enjoy your barbecues now!

Mosquitoes thrive in temperatures above 70. The hotter the better, because the warmer a water body becomes (think of your bird bath), the quicker a mosquito can grow from egg to adult. Buy your repellents!

Which insect-borne diseases are we at risk for?

A tick on a blade of grass

Here in the Midwest, we are relatively lucky. We don’t have deadly mosquito-borne diseases like malaria, dengue fever or chikungunya fever … yet. If the winters continually get warmer, the more tropical mosquitoes that spread these diseases will continue their migration north as they already are doing.

In Indiana, the most common mosquito-borne disease is West Nile virus, but only about 15 serious human cases are reported per year. However, for horses and birds, especially corvids like ravens, crows and jays, it is more of a concern.

The other menace to our health comes from biting ticks, especially the black-legged or deer tick. This tick has a long life (roughly three years) and can transmit Lyme disease in all its life cycle stages. Since 2017, not only did more than 47 percent of adult ticks in St. Joseph County test positive for the Lyme bacteria, but also 356 people were diagnosed with Lyme disease. If Lyme disease is left untreated, it can cause severe, chronic health complications (such as arthritis and heart and neurological problems) in humans and animals.

A bite from a black-legged tick, and many other types of ticks, especially the lone star tick, can also cause an allergy to red meat called alpha-gal syndrome (AGS). Although thought to be rare in Northern Indiana for now, AGS causes a difficult allergy to live with as many goods contain meat products, including some types of vitamin gummies, desserts, tattoo ink and medications. Furthermore, the symptoms of AGS can be confusing as they range from delayed anaphylactic shock to irritable bowel-like syndrome, and consequently, it can take an average of 7.5 years to be diagnosed.

When shopping for insect repellent sprays, what should people look for?

What types of repellents and insecticides are available changes every year.

When using the gold standard “arm-in-cage” test, which involves putting a naked arm painted with bug repellent into a cage of ravenous female mosquitoes, it is clear that anything with 25-30 percent DEET was the most effective. DEET’s repellency power also lasts the longest — sometimes exceeding eight hours.

The good thing about DEET-based products is that they are also safe for use on young children (unlike lemon eucalyptus); just keep them away from anything plastic. DEET has a nasty habit of making plastic turn foggy like your watch face or phone screen protector!

There are other options should you want an alternative to DEET; look for products containing at least 30 percent oil of lemon eucalyptus, IR3535 or 20 percent picaridin, but be aware these products may have to be reapplied more frequently.

It is great to see that something like Consumer Reports exists, and its researchers have tackled this exact question.

Beyond sprays, what other insect repellent products and methods work best?

A mosquito biting skin

To have an evening on your porch with fewer ankle-biting mosquitoes, in addition to using repellents and assuming you don’t mind the smell of citronella, you could get some big citronella candles and place them on the floor so the scent and smoke curl around your feet. Better yet, sit downwind from a fan so it blows the smoke into the flight path of the upwind-flying mosquitoes hunting for human scents.

An interesting way to suppress mosquito numbers and other insects is to encourage a healthy population of mosquito-eating predators like bats and swallows near your home. Also, designing your gardens with plants that mosquitoes dislike (such as lemongrass, citronella and lavender) can also sometimes help — but if you have pets, be careful as often these kinds of plants are also toxic to pets.

What other advice do you have for avoiding ticks? And mosquitoes?

For ticks, be vigilant. Get into the routine of checking yourself and your pets after strolling outside near longer grass or through the woods, especially where there are fallen oak leaves. Ticks love hiding in them! Check also that your bug repellent is tick-approved (look for an EPA number) as many are only specific for mosquitoes and other biting flies.

For mosquitoes, in the summer it is very hard to avoid them, but you can lessen your chances of becoming dinner by employing a few strategies. Make sure there is no standing water (e.g., planters with water trays, bird baths, ponds) near where you want to relax at dawn and dusk. Such water is a beacon to females wanting to lay their eggs and then, after, in their hunger-crazed state, catch a meal.

Another way to dampen down your mosquito attractiveness is to avoid wearing dark colors, especially black. Stick to brighter colors—many mosquitoes dislike yellows and whites, regardless of their night-biting or day-biting preferences.

Contact: Brandi Wampler, associate director of media relations, 574-631-2632, brandiwampler@nd.edu

Rare disease drug nitisinone makes human blood deadly to mosquitoes

2025-03-26T14:00:00-04:00

In the fight against malaria, controlling the mosquito population is crucial.

Several methods are currently used to reduce mosquito numbers and malaria risk. One of these includes the antiparasitic medication ivermectin. When mosquitoes ingest blood containing ivermectin, it shortens the insect’s lifespan and helps decrease the spread of malaria.

However, ivermectin has its own issues. Not only is it environmentally toxic, but also, when it is overused to treat people and animals with worm and parasite infections, resistance to ivermectin becomes a concern.

Now a study in Science Translational Medicine has identified another medication with the potential to suppress mosquito populations to help control malaria. Researchers found when patients take the drug nitisinone, their blood becomes deadly to mosquitoes.

“One way to stop the spread of diseases transmitted by insects is to make the blood of animals and humans toxic to these blood-feeding insects,” said Lee R. Haines, associate research professor of biological sciences at the University of Notre Dame, honorary fellow at the Liverpool 91��Ƶ of Tropical Medicine and co-lead author of the study. “Our findings suggest that using nitisinone could be a promising new complementary tool for controlling insect-borne diseases like malaria.”

Lee R. Haines, associate research professor of biological sciences at Notre Dame.

Typically, nitisinone is a medication for individuals with rare inherited diseases — such as alkaptonuria and tyrosinemia type 1 — whose bodies struggle to metabolize the amino acid tyrosine. The medication works by blocking the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD), preventing the build-up of harmful disease byproducts in the human body. When mosquitoes drink blood that contains nitisinone, the drug also blocks this crucial HPPD enzyme in their bodies. This prevents the mosquitoes from properly digesting the blood, causing them to quickly die.

The researchers analyzed the nitisinone dosing concentrations needed for killing mosquitoes, and how those results would stack up against ivermectin, the gold standard ectoparasitic drug (medication that specifically targets ectoparasites such as mosquitoes).

“We thought that if we wanted to go down this route, nitisinone had to perform better than ivermectin,” said Álvaro Acosta Serrano, professor of biological sciences at Notre Dame and co-corresponding author of the study. “Indeed, nitisinone performance was fantastic; it has a much longer half-life in human blood than ivermectin, which means its mosquitocidal activity remains circulating in the human body for much longer. This is critical when applied in the field for safety and economical reasons.”

The research team tested the mosquitocidal effect of nitisinone on female Anopheles gambiae mosquitoes, the primary mosquito species responsible for spreading malaria in many African countries. If these mosquitoes become infected with malaria parasites, they spread the disease when they feast on a human.

Álvaro Acosta Serrano, professor of biological sciences at Notre Dame.

To evaluate how the drug affected the mosquitoes when fed fresh human blood containing nitisinone, researchers collaborated with the Robert Gregory National Alkaptonuria Centre at the Royal Liverpool University Hospital. The center was performing nitisinone trials with people diagnosed with alkaptonuria, who then donated their blood for the study. Those taking nitisinone were found to have blood that was deadly to mosquitoes, which Haines describes as having a “hidden superpower.”

The research team collected data on how the drug was metabolized in peoples’ blood, allowing the team to fine-tune their modeling and provide pharmacological validation of nitisinone as a potential mosquito population control strategy.

Nitisinone was shown to last longer than ivermectin in the human bloodstream, and was able to kill not only mosquitoes of all ages — including the older ones that are most likely to transmit malaria — but also the hardy mosquitoes resistant to traditional insecticides.

“In the future, it could be advantageous to alternate both nitisinone and ivermectin for mosquito control,” Haines said. “For example, nitisinone could be employed in areas where ivermectin resistance persists or where ivermectin is already heavily used for livestock and humans.”

Next, the research team aims to explore a semi-field trial to determine what nitisinone dosages are best linked to mosquitocidal efficacy in the field.

“Nitisinone is a versatile compound that can also be used as an insecticide. What’s particularly interesting is that it specifically targets blood-sucking insects, making it an environmentally friendly option,” Acosta Serrano said.

As an unintended benefit, extending the use of nitisinone as a vector control tool could consequently increase drug production and decrease the price of the medication for patients suffering from rare genetic diseases in the tyrosine metabolism pathway.

The study was funded by the UK Medical Research Council, Biotechnology and Biological Sciences Research Council, Wellcome Trust Institutional Strategic Support Fund, the Medical Research Council Doctoral Training Partnership and the University of Glasgow Wellcome Centre for Integrative Parasitology.

In addition to Acosta Serrano and Haines, co-authors include Anna Trett (co-first), Jeremy Burrows, Clair Rose, Natalia García, Giancarlo Biagini and Ghaith Aljayyoussi (co-corresponding) from the Liverpool 91��Ƶ of Tropical Medicine; Dagmara McGuinness, Clément Regnault and Michael Barrett from the University of Glasgow Wellcome Centre for Integrative Parasitology; Didier Leroy and Jeremy Burrows from the Medicines for Malaria Venture; Marcos Sterkel from the Universidad Nacional de La Plata; and Lakshminarayan Ranganath from the Royal Liverpool University Hospital.

This research was primarily conducted by Haines, Trett, Aljayyoussi and Acosta Serrano at the Liverpool 91��Ƶ of Tropical Medicine.

Contact: Brandi Wampler, associate director of media relations, 574-631-2632, brandiwampler@nd.edu

Walk the Walk Week prayer service emphasizes the power of love, call to uplift one another

2025-02-03T11:17:00-05:00

To kick off the 10th annual Walk the Walk Week, the University of Notre Dame hosted a candlelight prayer service in the Basilica of the Sacred Heart attended by students, faculty, staff and local community members on Monday (Jan. 27). University President Rev. Robert A. Dowd, C.S.C., presided over the evening of prayer and reflection. Claire Babineaux-Fontenot, CEO of Feeding America and 2024 Laetare Medalist, offered the keynote reflection.

In his opening prayer, Father Dowd invited the audience to remember Rev. Martin Luther King Jr.’s call to build the Beloved Community — a community based on love, justice and equal opportunity, where all people are treated with dignity and respect and where poverty, hunger and homelessness are eliminated.

“May your Holy Spirit remind us all that you show no partiality toward nationality, race, ethnicity or gender. For us to do so is to go against your great commandment of love toward one another.

We pray that the Church will not be complicit in injustice by being silent, but that it can rise up with a prophetic voice that speaks with integrity and advances the values of your Kingdom,” said Father Dowd.

Following a reading from Luke’s Gospel (Luke 18:1-8), Babineaux-Fontenot offered the keynote reflection, focusing on the question at the center of this year’s Notre Dame Forum, “What do we owe each other?”

Exploring this theme through the lens of the names we have each been given, Babineaux-Fontenot shared stories of the names in her family, including those of her son, her husband and her own name. Babineaux-Fontenot, who hails from Louisiana, is named after her great-grandmother, Clarice Richard, a woman of extraordinary courage and fortitude, who, as an enslaved woman, protected her daughter by bearing an inhumane punishment on her behalf. Babineaux-Fontenot reflected on the significance of carrying a family name that reflects such great love in action.

Babineaux-Fontenot also explored the significance of the terms “Christian” and “Catholic.” She observed that in calling ourselves Christian, we are called to love as Christ loved.

Claire Babineaux-Fontenot, CEO of Feeding America and the 2024 Laetare Medalist, speaks at the 2025 Walk the Walk Week prayer service.

“I’m struck by the fact that He did not only tell us to love the people we like. He told us to love and pray for our enemies,” Babineaux-Fontenot said. “I understand that this can feel like a tall order, but He also taught us that we should seek redemption because He understood that none of us would be perfect at any of this.”

In closing, Babineaux-Fontenot reflected on Catholic social teaching, with its emphasis on a preferential option for the poor and a commitment to serve the most vulnerable. As CEO of Feeding America, Babineaux-Fontenot described witnessing kindness, generosity and compassion in action.

“I am buoyed by what I see in us and by what I have the opportunity to do with us,” she said. “If I had to boil down the lessons that I hope you hear from what I believe Christ is telling us, if it had to be reduced to just one word…it would be love.”

Following Babineaux-Fontenot’s reflections, Father Dowd invited student readers to offer prayers of intercession.

“God calls the people of the world into one human family, trusting in the Lord’s desire that we might all be one,” he said. “Let us offer our prayers to God for justice, healing and peace.”

Intercessions were offered in multiple languages including French, Igbo, Irish, Mandarin, Polish, Portuguese and Spanish.

The University’s Voices of Faith Gospel Choir provided the music for the prayer service.

At the conclusion of the service, those in attendance were invited to participate in the annual candlelight march to the Sacred Heart of Jesus statue. Walking along paths lit by luminaria, marchers placed their candles at the foot of the statue in silent prayer for peace, justice and unity.

Babineaux-Fontenot has served as CEO of Feeding America since 2018, and has spent decades as a leader and advocate dedicated to combating hunger, addressing food insecurity, and strengthening local communities. Feeding America is a national network of more than 200 food banks and 60,000 charitable and faith-based partners, and works to rescue, store and distribute food to more than 49 million people facing hunger each year. Babineaux-Fontenot has led the organization through a number of challenges, including navigating a global pandemic and the ensuing increase in food insecurity. Under her direction, Feeding America became the nation’s largest charitable organization in 2022, according to Forbes, and the network distributed 5.3 billion meals in 2023.

A recording of the prayer service is available online. Visit walkthewalk.nd.edu for information on upcoming events.

Social media platforms aren’t doing enough to stop harmful AI bots, research finds

2024-10-14T12:00:00-04:00

While artificial intelligence (AI) bots can serve a legitimate purpose on social media — such as marketing or customer service — some are designed to manipulate public discussion, incite hate speech, spread misinformation or enact fraud and scams. To combat potentially harmful bot activity, some platforms have published policies on using bots and created technical mechanisms to enforce those policies.

But are those policies and mechanisms enough to keep social media users safe?

Paul Brenner, Director in the Center for Research Computing at the University of Notre Dame (Photo by Barbara Johnston/University of Notre Dame)

New research from the University of Notre Dame analyzed the AI bot policies and mechanisms of eight social media platforms: LinkedIn, Mastodon, Reddit, TikTok, X (formerly known as Twitter) and Meta platforms Facebook, Instagram and Threads. Then researchers attempted to launch bots to test bot policy enforcement processes.

The researchers successfully published a benign “test” post from a bot on every platform.

“As computer scientists, we know how these bots are created, how they get plugged in and how malicious they can be, but we hoped the social media platforms would block or shut the bots down and it wouldn’t really be a problem,” said Paul Brenner, a faculty member and director in the Center for Research Computing at Notre Dame and senior author of the study. “So we took a look at what the platforms, often vaguely, state they do and then tested to see if they actually enforce their policies.”

The researchers found that the Meta platforms were the most difficult to launch bots on — it took multiple attempts to bypass their policy enforcement mechanisms. Although the researchers racked up three suspensions in the process, they were successful in launching a bot and posting a “test” post on their fourth attempt.

The only other platform that presented a modest challenge was TikTok, due to the platform’s frequent use of CAPTCHAs. But three platforms provided no challenge at all.

“Reddit, Mastodon and X were trivial,” Brenner said. “Despite what their policy says or the technical bot mechanisms they have, it was very easy to get a bot up and working on X. They aren’t effectively enforcing their policies.”

Social media bot policy enforcement testing framework used in the study.

As of the study’s publishing date, all test bot accounts and posts were still live. Brenner shared that interns, who had only a high school-level education and minimal training, were able to launch the test bots using technology that is readily available to the public, highlighting how easy it is to launch bots online.

Overall, the researchers concluded that none of the eight social media platforms tested are providing sufficient protection and monitoring to keep users safe from malicious bot activity. Brenner argued that laws, economic incentive structures, user education and technological advances are needed to protect the public from malicious bots.

“There needs to be U.S. legislation requiring platforms to identify human versus bot accounts because we know people can’t differentiate the two by themselves,” Brenner said. “The economics right now are skewed against this as the number of accounts on each platform are a basis of marketing revenue. This needs to be in front of policymakers.”

To create their bots, researchers used Selenium, which is a suite of tools for automating web browsers, and OpenAI’s GPT-4o and DALL-E 3. The research, published as a pre-print on ArXiv, was led by Kristina Radivojevic, a doctoral student at Notre Dame, and supported by CRC student interns Catrell Conley, Cormac Kennedy and Christopher McAleer.

Contact: Brandi Wampler, associate director of media relations, 574-631-2632, brandiwampler@nd.edu

ND Expert Sean Kassen: Statement on first FDA-approved treatment for Niemann-Pick Type C disease

2024-09-20T13:16:00-04:00

Today, the FDA announced the first approved treatment for Niemann-Pick Type C (NPC) disease: an oral medication named Miplyffa (arimoclomol). Sean Kassen, director of the Ara Parseghian Medical Research Fund at the University of Notre Dame, said this represents the beginning of a new and hopeful era for NPC families.

“It has been almost 30 years to the day since Michael, Marcia and Christa Parseghian were diagnosed with Niemann-Pick Type C disease, eventually taking their young lives. Since that time the Parseghian family and so many other families, researchers and volunteers have worked tirelessly to advance our understanding of NPC and bring treatments to those affected by this devastating disease. Today marks a momentous occasion with the FDA approval of Miplyffa and the start of a new era with the first official medication for the treatment of NPC disease. We will continue to fight for NPC families until this disease is eradicated,” Kassen said.

The APMRF is a non-profit organization dedicated to finding a treatment or cure for Niemann-Pick Type C disease. The organization is named in honor of Ara Parseghian, the much beloved and well-known Notre Dame football coach, and was founded by Mike and Cindy Parseghian, whose three children — Michael, Marcia and Christa — were diagnosed with NPC in 1994.

‘Silent’ mutations found to have repercussions beyond their own gene

2024-08-28T12:09:50-04:00

Genetic disorders — like cystic fibrosis and Huntington’s disease — are considered incurable, with gene mutations occurring in essentially every cell of the body.

Gene mutations occur when one nucleotide in a codon is switched. In non-synonymous mutations, this disrupts the codon’s function to code for its amino acid. In synonymous mutations, the codon still codes the correct amino acid. As such, these mutations are dubbed “silent” and often considered inconsequential to human health.

Patricia L. Clark (Photo by Matt Cashore/University of Notre Dame)

Now, researchers from the University of Notre Dame are adding new evidence to the emerging concept that these silent mutations may have crucial consequences. Their study, published in the Proceedings of the National Academy of Sciences, showed how a synonymous mutation in one gene can significantly affect a neighboring gene, increasing its protein production.

“The dogma in the field right now is that within the protein coding part of the genome, the only mutations that matter are the ones that change the DNA to code from one amino acid to another,” said Patricia L. Clark, the O’Hara Professor of Chemistry and Biochemistry at Notre Dame and lead author of the study. “That’s a very oversimplified view — to the point of being detrimental — of what matters.”

For this study, funded by Clark’s Director’s Pioneer Award from the National Institutes of Health, researchers experimented with the genome of the bacteria E. coli, as its small genome and simple cell structure make it more straightforward to ask fundamental questions about the impact of mutations than human cells. They created nine different synonymous versions of the CAT (Chloramphenicol acetyltransferase) gene, with each using different synonymous codons to encode the CAT protein.

When those different synonymous versions were expressed, they discovered that four of nine synonymous sequences affected the number of CAT proteins synthesized.

“Think about synonymous mutations like a huge quilt of possible DNA sequences that are all going to give you the same protein,” Clark said. “You can pick any part of the quilt and get the same protein, but will you get the same amount of protein? Will the protein fold be the same? Is the cell going to be healthy? This is what we were looking at.”

Clark’s initial hypothesis, as an expert in protein folding, was that these four synonymous mutations might be altering CAT protein folding, which occurs after gene expression. However, the researchers — including first author Anabel Rodriguez, then a doctoral student in Clark’s lab — went on to discover that the impact of the synonymous mutations occurs during the gene expression process, affecting the transcription of DNA to RNA.

“What Anabel showed was that the amount of CAT protein synthesis was correlated to the amount of CAT RNA synthesis,” Clark said. “This indicated that some synonymous mutations screwed up the synthesis of RNA from DNA. That Anabel was able to figure out this novel transcriptional regulation mechanism, while working in a lab with no previous experience studying transcription, is a remarkable achievement.”

The research showed that some of the synonymous mutations created cryptic transcription sites on the CAT DNA strand. RNA polymerase, the enzyme responsible for transcribing DNA to RNA, was binding to these cryptic transcription sites – instead of their expected binding site.

These polymerases synthesized an RNA that started within CAT, but extended to also encode the entire neighboring, upstream gene. In the case of CAT, the upstream gene encodes a repressor protein, so making more of it represses the expression of CAT.

The concept of a synonymous mutation impacting its own gene’s processes has only been considered in the last decade. So the idea that a synonymous mutation on one gene could also affect the transcription and translation processes of a neighboring gene is a significant expansion — and something Clark and her lab plan to further explore.

“There has been an increasing number of landmark studies that show how incomplete our understanding is on the impact of synonymous mutations. We should be considering how these mutations impact all diseases and genetic disorders,” Clark said. “I hope that our study will help accelerate the building of a comprehensive understanding.”

Next, the research team plans to analyze how some of the synonymous mutations of the CAT gene were able to recruit RNA polymerase to the cryptic binding location so efficiently. This is especially intriguing given that the currently available machine learning algorithms have not been able to accurately predict it.

Clark serves as an associate vice president of research and director of the Biophysics Instrumentation Core Facility at Notre Dame. Anabel Rodriguez, former graduate student in Clark’s lab and current instructor at Coastal Carolina Community College, was the lead author of the study.

Other study co-authors include Jacob Diehl, Christopher Bonar, Taylor Lundgren, McKenze Moss, Jun Li, Tijana Milenkovic, Paul Huber and Matthew Champion from Notre Dame; Gabriel Wright from the Milwaukee 91��Ƶ of Engineering; and Scott Emrich from the University of Tennessee.

Contact: Brandi Wampler, associate director of media relations, 574-631-2632, brandiwampler@nd.edu

Researchers develop affordable, rapid blood test for brain cancer

2024-08-27T10:30:00-04:00

Researchers at the University of Notre Dame have developed a novel, automated device capable of diagnosing glioblastoma, a fast-growing and incurable brain cancer, in less than an hour. The average glioblastoma patient survives 12-18 months after diagnosis.

The crux of the diagnostic is a biochip that uses electrokinetic technology to detect biomarkers, or active Epidermal Growth Factor Receptors (EGFRs), which are overexpressed in certain cancers such as glioblastoma and found in extracellular vesicles.

“Extracellular vesicles or exosomes are unique nanoparticles secreted by cells. They are big — 10 to 50 times bigger than a molecule — and they have a weak charge. Our technology was specifically designed for these nanoparticles, using their features to our advantage,” said Hsueh-Chia Chang, the Bayer Professor of Chemical and Biomolecular Engineering at Notre Dame and lead author of the study about the diagnostic published in Communications Biology.

The challenge for researchers was two-fold: to develop a process that could distinguish between active and non-active EGFRs, and create a diagnostic technology that was sensitive yet selective in detecting active EGFRs on extracellular vesicles from blood samples.

Bayer Professor Hsueh-Chia Chang (Photo by Matt Cashore/University of Notre Dame)

To do this, researchers created a biochip that uses an inexpensive, electrokinetic sensor about the size of a ball in a ballpoint pen. Due to the size of the extracellular vesicles, antibodies on the sensor can form multiple bonds to the same extracellular vesicle. This method significantly enhances the sensitivity and selectivity of the diagnostic.

Then synthetic silica nanoparticles “report” the presence of active EGFRs on the captured extracellular vesicles, while bringing a high negative charge. When extracellular vesicles with active EGFRs are present, a voltage shift can be seen, indicating the presence of glioblastoma in the patient.

This charge-sensing strategy minimizes interference common in current sensor technologies that use electrochemical reactions or fluorescence.

“Our electrokinetic sensor allows us to do things other diagnostics cannot,” said Satyajyoti Senapati, a research associate professor of chemical and biomolecular engineering at Notre Dame and co-author of the study. “We can directly load blood without any pretreatment to isolate the extracellular vesicles because our sensor is not affected by other particles or molecules. It shows low noise and makes ours more sensitive for disease detection than other technologies.”

Research Associate Professor Satyajyoti Senapati (Photo by Matt Cashore/University of Notre Dame)

In total, the device includes three parts: an automation interface, a prototype of a portable machine that administers materials to run the test and the biochip. Each test requires a new biochip, but the automation interface and prototype are reusable.

Running one test takes under an hour, requiring only 100 microliters of blood. Each biochip costs less than $2 in materials to manufacture.

Although this diagnostic device was developed for glioblastoma, the researchers say it can be adapted for other types of biological nanoparticles. This opens up the possibility for the technology to detect a number of different biomarkers for other diseases. Chang said the team is exploring the technology for diagnosing pancreatic cancer and potentially other disorders such as cardiovascular disease, dementia and epilepsy.

“Our technique is not specific to glioblastoma, but it was particularly appropriate to start with it because of how deadly it is and the lack of early screening tests available,” Chang said. “Our hope is that if early detection is more feasible, then there is an increased chance of survival.”

Blood samples for testing the device were provided by the Centre for Research in Brain Cancer at the Olivia Newton-John Cancer Research Institute in Melbourne, Australia.

In addition to Chang and Senapati, other collaborators include former postdocs at Notre Dame Nalin Maniya and Sonu Kumar; Jeffrey Franklin, James Higginbotham and Robert Coffey from Vanderbilt University; and Andrew Scott and Hui Gan from the Olivia Newton-John Cancer Research Institute and La Trobe University. The study was funded by the National Institutes of Health Common Fund.

Chang and Senapati are affiliated with Notre Dame’s Berthiaume Institute for Precision Health, the Harper Cancer Research Institute and NDnano.

Contact: Brandi Wampler, associate director of media relations, 574-631-2632, brandiwampler@nd.edu

Overburdened caseworkers put foster youths’ online safety on the back burner

2024-06-27T09:32:57-04:00

Foster parents and caseworkers agree: Sexual-related risks are the top concern for online safety for youths in the U.S. child welfare system. But how these two groups approach technology access and other online risks is conflicted, according to research from the University of Notre Dame.

Karla Badillo-Urquiola (Photo by Barbara Johnston/University of Notre Dame)

In a study led by Karla Badillo-Urquiola, the Clare Boothe Luce Assistant Professor of Computer Science and Engineering at Notre Dame, 32 caseworkers across the U.S. were interviewed about the online risks encountered by adolescents ages 13-17 in foster care. Caseworkers shared how they are trained to manage online safety and the major challenges they face in their roles. Badillo-Urquiola then compared the results to her previous study, which included interviews with 29 foster parents of 42 foster teens on similar topics.

The research published in the Proceedings of the ACM on Human-Computer Interaction showed that caseworkers are mostly concerned with online activity that facilitates offline, physical risks such as sex trafficking, running away, illegal drug activity and physical fights. Additionally, caseworkers perceive technology as a facilitator for contacting unsafe people, such as previous abusers, and engaging in risky communication with strangers. Harassment like cyberbullying and more general online risks are considered secondary concerns, which caseworkers reported they don’t receive training for.

Both foster parents and caseworkers reported being overburdened with other challenges, forcing them to put online safety as a low priority.

“Foster parents shared that they don’t receive enough support from their caseworkers, but caseworkers said they are struggling too, with large caseloads and focusing on keeping kids physically safe,” Badillo-Urquiola said. “Online safety becomes an afterthought.”

In the U.S. child welfare system, caseworkers are legally responsible for the physical and social-emotional well-being of foster youths, with authority and responsibility over a child’s case. They also receive intense, mandatory training about sexual risks and sex trafficking for foster youth, but many depend on their personal experience instead when navigating these concerns.

Some caseworkers called the training outdated and obsolete due to technology advancing too quickly.

Meanwhile, foster parents receive no training and believe they do not get appropriate guidance from their caseworkers to address online safety concerns. However, the research showed that foster parents were more aware of foster youths’ interactions and experiences online, but they did not have the authority and preparation to manage these situations effectively.

“We see this tension between giving youth in foster care normalcy and keeping them safe,” Badillo-Urquiola said. “Foster parents may want to give foster children a phone because their other children have one and so do other teens, but the parents don’t want the foster child to fall into risky behaviors. The parents don’t know what measures to put in place that provides online access but keeps foster youth safe.”

Unfortunately, a lack of experience and a fear of online risks often cause foster parents to completely revoke access to technology for foster youths, contrary to the “normalcy” policies the U.S. child welfare system calls for.

“We get health services online, apply for jobs online, or even to buy a car you may want access to the internet. It’s also a way to connect and have a social system,” Badillo-Urquiola said. “Restricting technology so much can actually hinder the life skills that foster youth need.”

The study argues that the prioritization of physical safety over online and emotional well-being of foster youths is rooted in a lack of resources and support for caseworkers.

To help improve online safety for foster youths, the researchers proposed multiple socio-technical systems such as collaborative technologies for caseworkers and foster parents, a centralized incidents database to consolidate problem resolutions and best practices, online support forums for caseworkers and foster parents to connect and learn from each other, and training modules for caseworkers, foster parents and foster youths.

“Our world is shifting and society is becoming so technologically advanced, but our child welfare system isn’t advancing with it,” Badillo-Urquiola said. “The child welfare system is not supporting the challenges caseworkers, foster parents and foster youth are facing.”

This research was a multi-institutional collaboration among Notre Dame’s Badillo-Urquiola, Vanderbilt University’s Zainab Agha and Pamela J. Wisniewski, University of Central Florida’s Denielle Abaquita and University of Colorado’s Scott B. Harpin.

Contact: Brandi Wampler, associate director of media relations, 574-631-2632, brandiwampler@nd.edu

Researchers identify factors that heighten risk for catheter-associated urinary tract infections and sepsis

2024-05-30T13:49:00-04:00

Urinary catheters are required for nearly every surgical procedure. However, a major challenge for the health care industry is predicting who may develop catheter-associated urinary tract infections (CAUTIs) and when these infections may lead to death.

Now, a study from the University of Notre Dame has identified a population that is more susceptible to developing a CAUTI.

Researchers showed that models with fibrinolytic deficiencies, or conditions that cause overactivation of the protein fibrin, had increased risk for developing severe and persistent CAUTIs. Additionally, they found these same models were more likely to develop sepsis.

Fibrin is vital in the formation of blood clots when the body attempts to repair injuries. When injured, the body calls on a process that uses fibrin to repair a wound, creating a fibrous structure to prevent bleeding during the healing process.

Ana Lidia Flores-Mireles, the Hawk Assistant Professor of Biological Sciences at Notre Dame, studied how this healing process could promote infection during urinary catheterization in animal models.

“A urinary catheter is constantly rubbing against bladder tissue, causing continuous inflammation and mechanical damage,” Flores-Mireles said. “The body will activate healing for the damaged bladder by recruiting the protein fibrinogen from the bloodstream. Fibrinogen will convert into fibrin, which creates net-like structures that accumulate where pathogens then colonize and promote persistent infection.”

The study published in Nature Communications found that the more fibrin “nets” the body creates, the more susceptible the model was to high pathogen colonization and the more fibrinogen was found in the circulatory system. As the amount of fibrinogen or fibrin increases in the bloodstream, the more likely a CAUTI is to spread to other organs and tissue.

However, when the researchers blocked fibrinogen recruitment or accumulation, it reduced CAUTIs because the pathogens needed the fibrin net-like structure to survive and persist.

Hawk Assistant Professor Ana Lidia Flores-Mireles (Photo by Matt Cashore/University of Notre Dame)

The research suggests that catheterized patients given antifibrinolytic medications, or drugs that discourage bleeding, could be at a higher risk for developing a CAUTI. Antifibrinolytic medications are often used to treat postpartum hemorrhages, traumatic injuries and other surgical procedures — all of which could require catheters when treated.

Flores-Mireles believes that this study can be applied to better prevent and manage human CAUTI, especially due to the current lack of consensus on best practices for CAUTI treatment.

“We strongly believe these findings provide key data to inform urinary catheterization guidelines in health care facilities and intensive care units, which will provide a higher quality of life to patients and minimize risk for complications,” Flores-Mireles said.

To help prevent CAUTIs, Flores-Mireles and her lab are developing a novel catheter that minimizes the inflammation and mechanical damage caused by typical catheters, preventing fibrin structures from forming and pathogens from causing infection.

In addition to Flores-Mireles, the study, “Fibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI,” was co-authored by Notre Dame’s Francis Castellino, Deborah Donahue, Victoria Ploplis, Jonathan Molina, Andrew Paik, Kurt Kohler, Christopher Gager, Marissa Andersen, Ellsa Wongso and Elizabeth Lucas; Washington University’s Wei Xu, Michael Caparon, Scott J. Hultgren, Karla Bergeron, Aleksandra Klim and Alana Desai; and the University of North Carolina’s Matthew Flick. Mireles, Castellino, Donahue and Ploplis are affiliated with Notre Dame’s W.M. Keck Center for Transgene Research.

Contact: Brandi Wampler, associate director of media relations, 574-631-2632, brandiwampler@nd.edu

AI browser plug-ins to help consumers improve digital privacy literacy, combat manipulative design

2024-05-29T14:25:00-04:00

Researchers at the University of Notre Dame are developing artificial intelligence tools that help consumers understand how they are being exploited as they navigate online platforms. The goal is to boost the digital literacy of end users so they can better control how they interact with these websites.

In a recent study, participants were invited to experiment with online privacy settings without consequence. To test how different data privacy settings work, the researchers created a Chrome browser plug-in called Privacy Sandbox that replaced participant data with personas generated by GPT-4, a large language model from OpenAI.

With Privacy Sandbox, participants could interact with different websites, such as social media platforms or news outlets. As they navigated to various sites, the browser plug-in applied AI-generated data, making it more obvious for participants to see how they were targeted based on their supposed age, race, location, income, household size and more.

“From a user perspective, allowing the platform’s access to private data may be appealing because you could get better content out of it, but once you turn it on, you cannot get that data back. Once you do, the site already knows where you live,” said Toby Li, assistant professor of computer science and engineering and a faculty affiliate at the Lucy Family Institute for Data & Society at Notre Dame, who led the research. “This is something that we wanted participants to understand, figure out whether the setting is worth it in a risk-free environment, and allow them to make informed decisions.”

Another study looked at dark patterns — or the design features on digital platforms that subtly nudge users to perform specific actions — and how they are used on websites to manipulate customers. For the study, Li and his team looked at how dark patterns are applied by interface designers to encourage people to consume more content or make impulsive purchasing decisions.

The researchers developed a Chrome browser plug-in dubbed Dark Pita to identify dark patterns on five popular online platforms: Amazon, YouTube, Netflix, Facebook and X.

The Dark Pita browser plug-in detects dark pattern designs, notifies the user and allows the user to customize their online experience.

Using machine learning, the plug-in would first notify study participants that a dark pattern was detected. It would then identify the threat susceptibility of the dark pattern and explain the impact of the dark pattern — financial loss, invasion of privacy or cognitive burden. Dark Pita would then give participants the option to “take action” by modifying the website code through an easy-to-use interface to change the deceptive design features of the site and explain the effect of the modification.

The researchers plan to eventually make both browser plug-ins, Privacy Sandbox and Dark Pita, available to the public. Li believes these tools are great examples of how the use of AI can be democratized for regular users to benefit society.

“Companies will increasingly use AI to their advantage, which will continue to widen the power gap between them and users. So with our research, we are exploring how we can give back power to the public by allowing them to use AI tools in their best interest against the existing oppressive algorithms. This ‘fight fire with fire’ approach should level the playing field a little bit,” Li said.

“An empathy-based sandbox approach to bridge the privacy gap among attitudes, goals, knowledge, and behaviors” was presented this month at the 2024 Association of Computing Machinery CHI Conference. Led by Li, fellow study co-authors include Chaoran Chen and Yanfang (Fanny) Ye from Notre Dame, Weijun Li from Zhejiang University, Wenxin Song at the Chinese University of Hong Kong and Yaxing Yao at Virginia Tech.

The study “From awareness to action: Exploring end-user empowerment interventions for dark patterns in UX,” led by Li, has been published in the Proceedings of the ACM on Human-Computer Interaction (CSCW 2024). Co-authors include Yuwen Lu from Notre Dame, Chao Zhang from Cornell University, Yuewen Yang from Cornell Tech and Yao from Virginia Tech.

This research was funded by a Google Research Scholar Award, a Google PSS Privacy Research Award and the National Science Foundation.

Contact: Brandi Wampler, associate director of media relations, 574-631-2632, brandiwampler@nd.edu

Bishop Rhoades: 2024 Benediction

2024-05-19T11:10:00-04:00

Bishop Rhoades: Today is the great solemnity of Pentecost. I invite you to please stand for this special blessing.

The Lord be with you.

All: And with your spirit.

Bishop: May God, the Father of light, who was pleased to enlighten the minds of the disciples by the outpouring of the Holy Spirit, the Paraclete, grant you gladness by His blessings and make you always abound with the gifts of the same Spirit.

All: Amen.

Bishop: May the wondrous flame that appeared above the disciples, powerfully cleanse your hearts from every evil and pervade them with its purifying light.

All: Amen.

Bishop: And may God, who has been pleased to unite many tongues in the profession of one faith, give you perseverance in that same faith and, by believing, may you journey from hope to clear vision.

All: Amen.

Bishop: And may the blessing of almighty God, the Father, and the Son, and the Holy Spirit come down on you and remain with you forever.

All: Amen.

John J. Brennan: 2024 Citation for Laetare Medalist Claire Babineaux-Fontenot

2024-05-19T10:48:00-04:00

Madam,

Animated by your faith and spirit of servant leadership, you have worked tirelessly to end the hunger crisis in the United States. Under your visionary leadership as chief executive officer, Feeding America has become the largest charitable organization in the U.S., distributing food to more than 49 million people facing hunger each year.

It is a cause that is close to your heart. Growing up as one of 108 siblings — thats 108 siblings who arrived in your family through a combination of birth, foster care and adoption — you saw firsthand the impact of the neglect, abuse and food insecurity many of your siblings faced before joining your home. And you witnessed the transformation that occurs when faithful servants of God feed the hungry and welcome the vulnerable to the table.

As the granddaughter of sharecroppers, you were not only the first in your family to attend college, but also in the first generation to finish high school. Your abiding faith in the power of education led you to complete both a Juris Doctor and a Master of Laws in taxation.

And almost 10 years ago, having reached the top rungs of the corporate ladder, while serving as global treasurer and executive vice president of finance for Walmart, you were called to a higher purpose. You did not hesitate to leave that world behind and make a leap of faith.

You have shepherded Feeding America through many challenges, including a global pandemic and the ensuing increase in food insecurity. And through it all, you have become a beacon of hope, inspiring many with your vision of a nation “where no one — no one — has to wonder where their next meal is coming from.”

In celebration of your steadfast dedication to those most in need, your remarkable compassion and generosity of spirit, and your embodiment of Christ’s love, the University of Notre Dame rejoices to confer its highest honor, the Laetare Medal

On Claire Babineaux-Fontenot, Chicago, Illinois

Isabela Tasende: 2024 Valedictory Address

2024-05-19T10:06:50-04:00

Esteemed guests, distinguished faculty and staff, friends and loved ones, bienvenidos! Welcome to the University of Notre Dame's 2024 graduation ceremony.

Fellow graduates, it is an honor and a privilege to share this moment with you. Today, we celebrate the end of our time at Our Lady's University. Yet this ceremony is not just one of graduation, but of commencement. It marks both an end and a beginning. So, as we reminisce on the roads we have traveled and welcome those that lie ahead, I want to start with a thank you: Class of 2024, thank you for giving me hope.

When I boarded my first flight to Notre Dame after nine long months in lockdown, I was nervous about entering this new environment. I had done my research, and so I knew two very important statistics: one, temperatures routinely dip below 70° in South Bend, and two, a majority of our student body played varsity sports in high school—neither of which, I, a Panamanian theater kid, felt equipped to deal with. Yet as I adapted to this new space, I quickly realized the most pivotal lessons Notre Dame had to offer revolved not just around academics, but on finding the courage to have hope amid hardship. Today, I wish to share three of these with you: Hope is not passive. Hope is not naive. And most surprisingly, hope comes not just from our successes against injustice, but from the love we share and the communities we build along the way.

First, hope is not passive. Rather, it calls us to act—to find the courage to put learning at the service of justice. If our time at Notre Dame is any indication, every one of us has the potential for greatness. Today, let us celebrate all our class has achieved to give us hope for a brighter future. Let's celebrate Lucas Barreto, whose fervent commitment to environment-centered design led him to secure dependable and sustainable energy sources for his community in Puerto Rico. Let's celebrate Luzolo Matundu, who through her participation in initiatives like Walk the Walk sought to protect the dignity of every student on this campus, regardless of their background. Let's celebrate Luke Linder, whose hard work and dedication led him to become a two-time national champion in fencing, upholding a legacy of excellence for Notre Dame Athletics. From leadership boards to D1 sports, in research and scholarship, we've continually stretched the boundaries of what we thought possible.

With incredible faculty, facilities, and labs, Our Lady has supported our pursuit of these achievements. The inauguration of the University's Democracy Initiative further reminds us of its commitment to empower us to tackle pressing global issues. And as a member of the Class of 2024, I am proud to say that we have not taken these opportunities for granted. Rather, we have worked hard to make the best out of every program and club this institution offers, dedicating time for event planning and mentorship on top of a full course load. We've applied these skills in practical settings, clocking long hours over the summer in prestigious internships, labs, and service projects. Notre Dame students know how to give up comfort in the name of growth. With hard work and opportunity, we have achieved great things. But we have not done so alone, and now is the time to give thanks. We have also been supported by incredible families, mentors, and peers, whose compassion and heart push us to grow in new and exciting ways.

As the child of two brilliant, devoted, and hard-working immigrants, I know precisely what it's like to have gratitude motivate discipline. Just so, the privilege of a Notre Dame education calls us out of complacency and into responsibility—to do what we can with what we have been given, and to give back to those who have made our journeys possible. Our gratitude for Notre Dame's commitment to education and community underlies our responsibility to pay it forward. We put love into action whenever we lend someone a hand, and thus assert Notre Dame's legacy in the world.

Second, hope is not naive; it is not an avoidance of the world's challenges or injustices. Rather, it is in reckoning with them that we find the courage to bring change. I, for one, can say that these challenges have shaped every aspect of my life. They have shaped my heart, as my family's history has made it difficult to find identity and belonging amid different cultures. I grew up in Panama City, Panama, with Venezuelan and Puerto Rican parents, and Cuban and Spanish grandparents. Memories of my grandfather reading poems about home, longing, and the loss of his country to dictatorship, remind me of how easy it can be to lose hope in light of distance, and to fight to retain who you are in light of displacement. Challenges have shaped my intellectual life, as in Panama, I worked to start an organization that helps young mothers finish their education.

At Notre Dame, I was humbled by the opportunity to translate this passion into research, working with Doctor Abby Córdova and the Kellogg Institute to study gender-based violence. But the more I learned about the depth of embedded injustices, the more I struggled to remain hopeful—What can I do in light of systemic barriers to change? Finally, challenges affected my spirit when at 17, I lost my best friend Paola in an accident. Upon arriving at Notre Dame, our community faced the loss of Valeria Espinel and Olivia Rojas—two friends we grieve not just for the conversations we had, but for all those we did not get to. How can we retain hope if nothing can prepare us for loss?

While in different forms, we have all faced challenges we cannot control. For many, these experiences came while abroad, learning to face loneliness and discover one's identity amid cultural differences. For others, service experiences opened their eyes to a world of injustice, and the distance that often hinders understanding. Inside each of us is an inner world full of all those things we have overcome, yet never make it to our resume. It is precisely these challenges that often erode our hope, for it is easy to become desensitized to injustice when no amount of achievement will allow us to bring change. Yet, I pose that during our time here, our deepest learning and perhaps deepest growth has come from facing that very question: how can we maintain hope when "greatness" is no longer enough?

This brings me to the third and most important lesson I've learned while here: Hope comes not just from our successes against injustice, but from the love we share along the way. Our Lady has taught us that we build hope through connection, for it is love—a commitment to the good of the other—that allows us to find meaning. My family's history allowed me to see the beauty in diversity and intergenerational understanding—of finding community where we never thought it possible. My experiences researching gender-based violence allowed me to contextualize volunteering at immigration clinics, where I learned how accompanying one migrant can make the brunt of injustice easier to bear.

Finally, my experiences with loss remind me of the beauty in being remembered, and what it is that we truly leave behind. They pushed me to ask, what does it mean to live a meaningful life? At Notre Dame, we have learned that our worth is not measured by statistics, but rather in the myriad ways we act as a light to others, making their worlds just a little bit brighter. This looks like sitting with your friends in Hes for their late-night Orgo "grind-sesh”. It looks like Lane Obringer, taking the time to walk with her fellow classmates and learn about what matters most to them. It looks like accompaniment, and radically choosing to love those around you, because those are the relationships that give us hope.

So, what does it mean to be an ND graduate? It means we ask big questions on meaning and purpose. It means we seek community, and create a space for the integral and holistic development of those around us. It means we share the utmost care for the vulnerable, carrying a responsibility to use our talents to serve the common good. Most importantly, it means that we know who we are is more than what we do. That, in a world that measures us from before we learn to speak and where our own hunger for justice leaves us feeling hopeless in an unjust world—we know that our worth is tied not to the things we have accomplished, but to the light we bring into every interaction and connection. Our class serves as a testament to what can happen when you take that commitment to heart.

Class of 2024, our time here has demonstrated that we can and will accomplish great things. But as soon-to-be Notre Dame graduates, I think we can challenge ourselves to go beyond that: to think that maybe—we can strive not just to be great, but to be good. I'll end with my favorite quote often attributed to Saint Augustine: Hope has two beautiful daughters, anger and courage. Anger that things are the way they are, and courage to make them what they ought to be. Let us recognize the injustices around us that seem too large to conquer and all that lies beyond our control, but let us also have the courage to dive into that uncertainty—to approach pain with resilience, struggle with discipline, and hopelessness with connection.

We have already demonstrated our capacity to find community in the face of distance. This, in the end, is what gives me hope—not just that we will achieve great things in the face of adversity, because of that I am sure—but rather that we will find meaning in every life we touch along the way.

So let us hope to be a light in a dimming world, shooting for the moon while remembering to love the stars.

Cancer therapies show promise in combating tuberculosis

2024-03-25T15:00:00-04:00

What could cancer teach us about tuberculosis? That’s a question Meenal Datta has been chasing since she was a graduate student.

Once the body’s immune system is infected with tuberculosis, it forms granulomas — tight clusters of white blood cells — in an attempt to wall off the infection-causing bacteria in the lungs. But more often than not, granulomas do more harm than good.

Charged with analyzing the similarities between granulomas and tumors, Datta discovered that both are structurally and functionally abnormal. In 2015, she and other researchers looked at the vascular structures of granulomas and showed that they are compromised and leaky just like tumor blood vessels, which limits drug delivery and successful treatment in both diseases.

“It was the first time we showed definitively that there was this pathophysiological similarity between these two diseases that present with different causes and symptoms,” said Datta, assistant professor of aerospace and mechanical engineering at the University of Notre Dame. “Cancer doesn’t sound anything like an infectious disease. And yet, here are two different diseases with the same problem of dysfunctional blood vessels.”

Now a study from the same team at the University of Notre Dame, Massachusetts General Hospital and the National Institutes of Health has identified a combination of medications that may improve blood flow within granulomas, benefiting drug delivery. Published in the Proceedings of the National Academy of Sciences, the study leverages decades of cancer research to study tuberculosis-affected lung tissue and improve treatment.

“Much like in tumors, many of the blood vessels in granulomas are compressed or squeezed shut — just like if you stepped on your garden hose,” said Datta, the first author on the study. “In cancer, we know that happens because of the growing tumor mass and the supportive protein scaffolding it puts down, called matrix. We thought maybe the same thing was happening in tuberculosis.”

The study confirmed that a similar phenomenon is occurring in granulomas — too much cell mass and protein scaffolding. This impaired function makes blood flow through blood vessels nearly impossible, crippling the ability to get a medication to the tuberculosis disease site.

Datta and her collaborators used losartan, an affordable drug used to treat high blood pressure. However, it also has the beneficial side effect of reducing the amount of matrix being created inside a granuloma, thus opening the compressed blood vessels and restoring blood flow.

Researchers then combined losartan with bevacizumab, a drug used by cancer patients to stop the overproduction of poorly formed blood vessels. With this two-pronged medicinal approach, Datta and the team were able to make the granuloma blood vessels function and behave more normally.

When the researchers applied the host-directed therapies losartan and bevacizumab along with antibiotics, they showed improved drug delivery and antibiotic concentration within granulomas.

Additionally, Datta’s graduate student Maksym Zarodniuk analyzed genome sequencing data produced by the team, and found that even without antibiotics, there was a reduction in tuberculosis bacteria within the granulomas.

“When we gave just those host-directed therapies, we were getting good treatment benefit even without adding the antibiotics. Those therapies were promoting the body’s inflammatory response to fight against the bacteria, which we did not expect,” Datta said.

For Datta, this study caps off a stretch of tuberculosis research that started when she began her doctoral research at Massachusetts General Hospital and Harvard Medical 91��Ƶ in 2011, and has spanned multiple phases of her career. Tuberculosis, although largely controlled in the U.S., is still considered one of the deadliest infectious diseases worldwide.

“The advantage of the host-directed therapies we selected is that these agents or very similar drugs of the same class are already approved by regulatory agencies around the globe, and they are affordable,” Datta said. “We hope that our preclinical results will be found compelling enough to start a clinical trial to benefit tuberculosis patients.”

Today, Datta’s lab at the University of Notre Dame primarily focuses its research on understanding glioblastoma, a rare treatment-resistant brain cancer. Datta said that being an engineer allows her to cross into other areas of research and with a different perspective, making an excellent case for the importance of multidisciplinary research.

“I do believe that really is an advantage of being an engineer. It’s easier for me to sometimes make connections between contexts that seem disparate,” Datta said. “We depend on our life science and clinical colleagues to walk through those details, but engineers are very good at approaching complex problems from a simplified systems approach.”

The study, “Normalizing granuloma vasculature and matrix improves drug delivery and reduces bacterial burden in tuberculosis-infected rabbits,” was funded by the Bill & Melinda Gates Foundation and the National Institutes of Health. Datta is an affiliated member of Notre Dame’s Berthiaume Institute for Precision Health, Eck Institute for Global Health, Harper Cancer Research Institute, Lucy Family Institute for Data and Society, NDnano and Warren Center for Drug Discovery. Datta is an assistant professor in the following doctorate programs: aerospace and mechanical engineering, bioengineering, and materials science and engineering.

Contact: Brandi Wampler, associate director of media relations, 574-631-2632, brandiwampler@nd.edu

A vision of hope

2024-02-29T11:28:00-05:00

You don’t know what it is to be an advocate until you are one.

That was never more clear to Harry and Gail Koujaian than when their 5-year-old daughter, Hayley, began having difficulty with motor function, verbal communication, and sight words. Then she had her first seizure.

It took six years of patient advocacy—challenging inaccurate diagnoses, meeting with doctors, pushing for medical tests, becoming “parent scientists,” scheduling surgeries, and planning regular therapy sessions—before the Koujaians would get the correct diagnosis: Niemann-Pick disease type C.

Niemann-Pick disease type C, or NPC, is an inherited, progressive genetic disorder caused by the body’s inability to transport cholesterol and other fatty substances inside of cells. The result is an irreversible dementia-like disease that affects a child’s ability to walk, talk, swallow, and think. The disorder is very rare, affecting one in 120,000 people, and death typically occurs before or during adolescence.

Hayley was diagnosed with the terminal disorder at the age of 11. Her older brother, Alec, was diagnosed shortly thereafter at 13.

The Koujaian family’s experience is all too common. With more than 7,000 different diseases classified as “rare,” 10 percent of the population is likely to encounter a diagnostic odyssey of unnecessary tests and wrong diagnoses in their push for effective care.

Read the story

AI among us: Social media users struggle to identify AI bots during political discourse

2024-02-27T10:29:00-05:00

Artificial intelligence bots have already permeated social media. But can users tell who is human and who is not?

Researchers at the University of Notre Dame conducted a study using AI bots based on large language models — a type of AI developed for language understanding and text generation — and asked human and AI bot participants to engage in political discourse on a customized and self-hosted instance of Mastodon, a social networking platform.

The experiment was conducted in three rounds with each round lasting four days. After every round, human participants were asked to identify which accounts they believed were AI bots.

Fifty-eight percent of the time, the participants got it wrong.

“They knew they were interacting with both humans and AI bots and were tasked to identify each bot’s true nature, and less than half of their predictions were right,” said Paul Brenner, a faculty member and director in the Center for Research Computing at Notre Dame and senior author of the study. “We know that if information is coming from another human participating in a conversation, the impact is stronger than an abstract comment or reference. These AI bots are more likely to be successful in spreading misinformation because we can’t detect them.”

The study used different LLM-based AI models for each round of the study: GPT-4 from OpenAI, Llama-2-Chat from Meta and Claude 2 from Anthropic. The AI bots were customized with 10 different personas that included realistic, varied personal profiles and perspectives on global politics.

The bots were directed to offer commentary on world events based on assigned characteristics, to comment concisely and to link global events to personal experiences. Each persona’s design was based on past human-assisted bot accounts that had been successful in spreading misinformation online.

Paul Brenner

The researchers noted that when it came to identifying which accounts were AI bots, the specific LLM platform being used had little to no impact on participant predictions.

“We assumed that the Llama-2 model would be weaker because it is a smaller model, not necessarily as capable at answering deep questions or writing long articles. But it turns out that when you’re just chatting on social media, it’s fairly indistinguishable,” Brenner said. “That’s concerning because it’s an open-access platform that anyone can download and modify. And it will only get better.”

Two of the most successful and least detected personas were characterized as females spreading opinions on social media about politics who were organized and capable of strategic thinking. The personas were developed to make a “significant impact on society by spreading misinformation on social media.” For researchers, this indicates that AI bots asked to be good at spreading misinformation are also good at deceiving people regarding their true nature.

Although people have been able to create new social media accounts to spread misinformation with human-assisted bots, Brenner said that with LLM-based AI models, users can do this many times over in a way that is significantly cheaper and faster with refined accuracy for how they want to manipulate people.

To prevent AI from spreading misinformation online, Brenner believes it will require a three-pronged approach that includes education, nationwide legislation and social media account validation policies. As for future research, he aims to form a research team to evaluate the impact of LLM-based AI models on adolescent mental health and develop strategies to combat their effects.

Additionally, the research team is planning for larger evaluations and is looking for more participants for its next round of experiments. To participate, email llmsamongus-list@nd.edu.

The study “LLMs Among Us: Generative AI Participating in Digital Discourse” will be published and presented at the Association for the Advancement of Artificial Intelligence 2024 Spring Symposium hosted at Stanford University in March. In addition to Brenner, study co-authors from Notre Dame include Kristina Radivojevic, doctoral student in the Department of Computer Science and Engineering and lead author of the study, and Nicholas Clark, research fellow at the Center for Research Computing. Funding for this research is provided by the Center for Research Computing and AnalytiXIN.

Contact: Brandi Wampler, associate director of media relations, 574-631-2632, brandiwampler@nd.edu

Notre Dame receives Chan Zuckerberg Initiative award for neurodegenerative disease research

2024-02-21T11:59:00-05:00

Cody Smith chats with a graduate student in his lab. (Matt Cashore/University of Notre Dame)

The University of Notre Dame has received a Collaborative Pairs Pilot Project Award from the Chan Zuckerberg Initiative to study genes that affect neurodegenerative diseases, such as Alzheimer’s disease.

This is Notre Dame’s first award from the Chan Zuckerberg Initiative.

The award will fund a partnership between Cody Smith, the Elizabeth and Michael Gallagher Associate Professor of Biological Sciences at Notre Dame and a 2017 Alfred P. Sloan Fellow, and Beth Stevens, member of the Broad Institute of MIT and Harvard and a 2015 MacArthur Fellow. With their combined expertise in neurological development, they will explore how gene expression and function changes with aging, allowing neurodegenerative diseases to occur.

“Instead of looking at an individual gene, our approach is to look at a suite of genes that work individually or together and decipher what their core function is,” Smith said. “By understanding their combined function we can get a better picture of what is happening in the brain and, eventually, why they enter disease states.”

Stevens’ team uses cutting-edge sequencing to identify multiple genes and how they are expressed at different ages. Her team will provide a list of genes to the Smith Lab, which will use advanced imaging approaches on a zebrafish model to analyze which genes are important for modifying microglia, or the cells that are responsible for regulating brain development and healing injured tissue. Stevens’ team will simultaneously analyze the genes in human microglia.

Together, the researchers will look at how those microglia shift into disease states and therefore may not work properly in defending the brain against neurodegenerative diseases.

“We don’t really know how specific risk genes change microglia function in disease. This collaborative project will allow us to develop new tools to track and manipulate microglia to better understand how genes relate to function and to identify conserved mechanistic pathways,” Stevens said.

The award will provide $200,000 over an 18-month period, and Smith and Stevens will also gain long-term access to the Chan Zuckerberg Initiative Neurodegeneration Challenge Network. The network offers support, mentoring and collaborative interactions with researchers across a broad range of fields to foster collaboration for tackling neurodegenerative disease.

Contact: Brandi Wampler, associate director of media relations, 574-631-2632, brandiwampler@nd.edu

SNAP recipients may struggle to meet dietary goals, especially in food deserts

2023-12-14T08:15:00-05:00

The Supplemental Nutrition Assistance Program (SNAP) is the nation’s largest nutrition program, helping 41 million participants afford “nutritious food essential to health and well-being.”

But a new study from the University of Notre Dame found that SNAP participants in low-income households may not be able to meet the nutrition levels set by the Dietary Guidelines for Americans (DGA).

The case study set out to examine whether SNAP participants would be able to afford a healthy diet based on DGA’s recommended nutritional values. The DGA was created by the U.S. Departments of Agriculture and Health and Human Services to advise Americans on what they should eat and drink to meet nutrient needs, promote health and prevent disease.

“Healthy eating is a critical problem, especially within low-income communities where there’s a combination of economic and geographic constraints making healthy and affordable food less attainable,” said Nitesh Chawla, director of the Lucy Family Institute for Data and Society and the Frank M. Freimann Professor of Computer Science and Engineering at Notre Dame. “Individuals working within these constraints live in food deserts, and they have to consider multiple factors as they make decisions about their family’s diet.”

As a baseline, the research team used the maximum SNAP allotment offered for a single person in Indiana as of October 2021, which was $250 per month. They divided this amount by day to determine what a person’s daily budget would be. Then the team created a linear programming model that considers product nutrition and price for items available within a nationwide grocery store chain in South Bend.

“We found that people essentially make trade-offs based on the information they have to try to stretch their funds and maximize nutrition,” said Ronald Metoyer, professor of computer science and engineering and vice president and associate provost for teaching and learning. “Our idea for this study was to use computation to aggregate all of the relevant information (e.g., inventory, prices and nutritional content) and use optimization to make those choices.”

Researchers took into consideration the cost per serving for a meal and the different diet guidelines for men and women ages 31-50, while also minimizing the cost of the diet however possible. Although they found it was possible to create a realistic woman’s diet that fits the monetary allotment of SNAP and the nutritional needs of the DGA, it was not possible to do the same for men.

The team also analyzed the trade-off between cost and nutritional value specifically for nutrients that Americans tend to overconsume: sodium, saturated fat and added sugars. To do this, they set the DGA’s parameters aside and selected only the cheapest food options to meet the SNAP budget. The researchers found a direct correlation between sodium and cost — as the cost of groceries decreases, the amount of sodium consumed increases.

Researchers also noted that the hardest DGA parameters to meet on a SNAP budget were daily vitamin and mineral intake needs.

“What we found was vitamins and minerals are very difficult to actually hit the dietary guidelines on,” said Joe Germino, a doctoral student in the Lucy Institute’s DIAL Lab who is advised by Chawla. “You have to make a conscious decision to go and find food items that are cheap enough and actually match your budget. It just adds another layer of complexity to an already difficult problem when you’re living in a food desert.”

Census data has identified 11 areas in St. Joseph County that can be identified as food deserts, or where a significant amount of people live more than a mile from the nearest supermarket. Residents living in and around the area have to consider the distance to full-service grocery stores as well as their access to transportation to purchase healthy foods.

These barriers are even more difficult to overcome for low-income households, which could create a higher reliance on alternative food sources such as food pantries. Although the per-person budget for SNAP recipients has increased since this study was conducted, due to other economic constraints such as inflation researchers believe that the results still apply for those relying on SNAP support today.

“The reason we chose South Bend is because we have areas that are considered food deserts and we are seeing this lack of food access happening within our own community,” said Annalisa Szymanski, a Lucy Graduate Scholar who is advised by Metoyer and a co-author on the study.

The study published in Frontiers in Big Data is just one way Notre Dame researchers are leveraging technology to tackle this national challenge of food access and insecurity through the Food Information Networks (FINS) project. Led by Metoyer, FINS is funded by the National Institute of Food and Agriculture. The project aims to thoroughly understand the barriers to access for healthy food, develop technological supports, and deploy and study interventions in South Bend and Detroit.

The project will culminate with an app that employs optimization methods to recommend and suggest healthier food items to people based on their dietary goals and their budgets. In the spring, researchers will pilot a version of the app in Rum Village, a neighborhood of South Bend. The goal is to test the app to see how that solution helps overcome transportation constraints. The pilot will partner with local Walmart grocery stores.

“Through the pilot, we’re testing to see if we promote different suggestions for healthier food products in the app, will that influence how people are eating? Or what if they know there is a healthier product on sale?” Szymanski said. “We want to see how this technology, when considering both dietary goals and budget, could realistically impact eating habits.”

The researchers are also looking into how the FINS project could leverage artificial intelligence, such as large language models, to create personalized diet recommendations.

Contact: Brandi Wampler, associate director of media relations, 574-631-2632, brandiwampler@nd.edu

Understudied cell in the brain could be key to treating glioblastoma

2023-12-12T08:15:00-05:00

Glioblastoma is one of the most treatment-resistant cancers, with those diagnosed surviving for less than two years.

In a new study in NPJ Genomic Medicine, researchers at the University of Notre Dame have found that a largely understudied cell could offer new insight into how the aggressive, primary brain cancer is able to resist immunotherapy.

“A decade ago, we didn’t even know perivascular fibroblasts existed within the brain, and not just in the lining of the skull,” said Meenal Datta, assistant professor of aerospace and mechanical engineering at Notre Dame and senior author on the study. “My lab’s expertise is examining tumors from an engineering and systems-based approach and looking at the novel mechanical features in rare cancers that may have been understudied or overlooked.”

Using standard bioinformatics and newer AI-based approaches, Datta’s TIME Lab began analyzing different genes expressed in the tumor microenvironment related to the extracellular matrix — or the scaffolding cells create to support future cell adhesion, migration, proliferation and differentiation — and other various cell types. What they found was a surprising, fairly new cell type: perivascular fibroblasts. These fibroblasts are typically found in the blood vessels of a healthy brain and deposit collagen to maintain the structural integrity and functionality of brain vessels.

“It was a serendipitous discovery,” said Maksym Zarodniuk, graduate student in the TIME Lab and the bioengineering doctorate program, and first author on the study. “We started in a completely different direction and stumbled upon this population of cells by using a combination of both bulk and single-cell RNA sequencing analyses of patient tumors.”

In their data, researchers were able to identify two groups of patients: those with a higher proportion of perivascular fibroblasts and those with significantly less. They found that brain cancer patients with more perivascular fibroblasts in their tumors were more likely to respond poorly to immunotherapies and have poor survival outcomes.

When exploring how this is possible, the researchers found that perivascular fibroblasts support the creation of an immunosuppressive tumor microenvironment, allowing the cancer to better evade the immune system. The fibroblasts may also help the cancer resist therapies — such as chemotherapy that targets dividing cells — by promoting stem-like cancer cells that rarely divide, which are believed to be a major source of tumor relapse and metastasis.

“Moving forward, we want to do new experiments to confirm what we found in this paper and provide some good ground to start thinking about how to improve response to immunotherapy,” Zarodniuk said.

Because perivascular fibroblasts are a part of a healthy brain’s vasculature, Datta believes that these cells are breaking off and getting close to or infiltrating the glioblastoma tumor. However, instead of supporting healthy brain function, these fibroblasts are getting reprogrammed and helping the tumor instead.

“Most people think about the brain as being very soft, with soft cells and a soft matrix. But by putting down these fibroblasts and making these very fibrous proteins, it gives us an entirely different perspective on the structure of the brain and how it can be taken advantage of by cancer cells originating in the same organ,” Datta said.

In addition to Datta and Zarodniuk, other Notre Dame collaborators include Jun Li, professor of applied and computational mathematics and statistics, who developed deep learning algorithms in support of this work; Xin Lu, the John M. and Mary Jo Boler Collegiate Associate Professor of Biological Sciences at Notre Dame; and Xander Steele, undergraduate student in the TIME Lab and a Grand Challenges Scholar.

Datta is an affiliated member of Notre Dame’s Berthiaume Institute for Precision Health, Eck Institute for Global Health, Harper Cancer Research Institute, Lucy Family Institute for Data and Society, NDnano and Warren Center for Drug Discovery. Datta is an assistant professor in the following doctorate programs: aerospace and mechancal engineering, bioengineering and materials science and engineering.

This work was funded by the National Cancer Institute.

Contact: Brandi Wampler, associate director of media relations, 574-631-2632, brandiwampler@nd.edu

Using patients’ own cells, researchers examine connection between fragile X syndrome, intellectual disability

2023-11-14T10:38:00-05:00

Although considered a rare disorder, fragile X syndrome is the most common genetic cause of intellectual disability in the world. Fragile X patients can have a range of mild to severe intellectual disability with the potential for other conditions such as autism, delayed motor development, hyperactivity, behavioral problems and seizures.

Although it’s well-known that fragile X is caused by the FMR1 gene, it’s less understood how the disorder physically affects brain development and function.

Christopher Patzke, the John M. and Mary Jo Boler Assistant Professor of Biological Sciences at the University of Notre Dame, is collaborating with fragile X patients and families to study the disorder.

“My lab is hoping to find an explanation of the disease symptoms in humans, looking at the disorder at the cellular and molecular level,” Patzke said.

By partnering with fragile X expert Dr. Elizabeth M. Berry-Kravis, professor of pediatrics at Rush University and a 1979 graduate of Notre Dame, the Patzke Lab has been able to collect patient tissue samples to create induced pluripotent stem cells. Because these stem cells mimic embryonic stem cells, the lab can then transform those cells into virtually any human cell the researchers want to study.

For this research, Patzke and his team are transforming pluripotent stem cells into brain cells that mimic neurons of someone with fragile X syndrome, creating a human model to study the genetic mutation’s effect on the brain.

Pictures of human neurons (with and without fragile X mutation) taken with a confocal microscope. The green dots are synapses.

“Most of the genes associated with intellectual disability encode for proteins that do something with synapses,” Patzke said. “So making a cell culture of these fragile X neurons allows us, in a way, to ‘zoom in’ to single cells and synapses, or the connections between neurons, and learn how these neurons communicate with one another.”

The researchers then compare a patient’s cell culture sample to a corrected-cell culture sample, made via gene editing, to analyze the differences between how the synapses function with and without the FMR1 gene mutation.

Although research into fragile X syndrome is not uncommon, many researchers use animal models to study the FMR1 gene. While some of the research has led to clinical trials, those results have yet to translate into effective benefits for humans. By using tissue from fragile X patients, the goal is to overcome this gap in discovery.

In addition to fragile X syndrome, the Patzke Lab is also studying other disorders that cause intellectual disability including Down syndrome and Kabuki syndrome, another rare disorder.

Patzke is affiliated with Notre Dame’s Boler-Parseghian Center for Rare and Neglected Diseases, among the first basic science rare disease research centers in the nation. Focused on both basic and translational research, the center works with families affected by rare diseases to combine studies of patient data and tissue with fundamental biological research in order to better understand disease, identify molecular targets and develop new diagnostics and treatments.

Contact: Brandi Wampler, associate director of media relations, 574-631-2632, brandiwampler@nd.edu