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Notre Dame launches two-year Master of Science in Global Health program

2021-08-17T09:00:00-04:00

A two-year Master of Science in Global Health program will leverage the University of Notre Dame’s historical strength in infectious disease research to help students solidify interdisciplinary careers that will address health issues worldwide.

The master’s program, which is a partnership among the Eck Institute for Global Health, Notre Dame College of Science and the Keough 91��Ƶ of Global Affairs, will begin accepting applications on Aug. 30, with the first class graduating in 2024.

“This program is going to expand the already excellent student research experience at Notre Dame,” said Dr. Bernard Nahlen, director of the Eck Institute for Global Health and professor in the Department of Biological Sciences. “Given the talent and skills among the faculty and their track record in global health, this is going to be a rich environment for students to come into.”

The University previously offered a one-year master’s program in global health. The expansion allows students more time to connect and shape their views of global health within the context of world events — including, but not limited to, upheaval from the COVID-19 pandemic. Additionally, a review of the program showed that expanding it to two years would allow more scheduling availability for international research and time for further coursework.

“The new design of the Master of Science in Global Health program represents an incredibly rich training environment,” said Laura Carlson, dean of the Graduate 91��Ƶ and professor of psychology. “It interlaces leadership and ethics into coursework that is then brought to life through students’ individualized research and fieldwork. At Notre Dame, we are driven by the conviction that each student matters, and their research matters. The M.S. in Global Health is a program in which students develop the skills, methods and habits of mind that will make each of them a force for good in the world.”

The expanded program will offer three areas of concentration: vector biology and parasitology, health governance and policy, and health analytics.

“With the two-year program, students will have more time to access a much broader range of courses that will better round out their knowledge of global health,” said Nahlen, who also envisions that the program will be a terminal degree for students specifically interested in careers in global health.

The new program will give students an entire summer to complete their research, and much of the year after to analyze and synthesize their results, said Michael Hildreth, interim dean of the College of Science.

“This new program should make for a much more intensive research experience that will be beneficial for their future careers,” Hildreth said.

Scott Appleby, the Marilyn Keough Dean of the Keough 91��Ƶ of Global Affairs, said the partnership with the Eck Institute will allow students from both the two-year program and Keough 91��Ƶ’s existing Master of Global Affairs program to graduate better prepared to collaborate with and serve people in a variety of geographical and cultural settings.

“Both the Eck Institute and the Keough 91��Ƶ understand that the health of the most vulnerable populations around the world is affected by the physical and psychological pressures associated with poverty and displacement, the Earth’s changing climate and the availability of natural resources, the sometimes inadequate government response to pandemics and plagues, and many other factors,” Appleby said. “So together ours is a holistic, context-specific approach to health and health care.”

Hildreth expects that Notre Dame’s history in vector biology research — research into how organisms, like mosquitos, transmit diseases — will be a draw for students, and Nahlen agrees.

“Notre Dame is developing a best-in-class program that will be the go-to place to get a degree in global health,” he said.

Interested students can learn more about the Eck Institute for Global Health, including opportunities for partial financial support, and may complete their applications through the Graduate 91��Ƶ starting Aug. 30.

Our genes shape our gut bacteria, new research shows

2021-07-08T15:00:00-04:00

Our gut microbiome — the ever-changing “rainforest” of bacteria living in our intestines — is primarily affected by our lifestyle, including what we eat or the medications we take, most studies show.

But a University of Notre Dame study has found a much greater genetic component at play than was once known.

In the study, published recently in Science, researchers discovered that most bacteria in the gut microbiome are heritable after looking at more than 16,000 gut microbiome profiles collected over 14 years from a long-studied population of baboons in Kenya’s Amboseli National Park. However, this heritability changes over time, across seasons and with age. The team also found that several of the microbiome traits heritable in baboons are also heritable in humans.

“The environment plays a bigger role in shaping the microbiome than your genes, but what this study does is move us away from the idea that genes play very little role in the microbiome to the idea that genes play a pervasive, if small, role,” said Elizabeth Archie, professor in the Department of Biological Sciences and a principal investigator on the study who is also affiliated with the Eck Institute for Global Health and the Environmental Change Initiative.

The gut microbiome performs several jobs. In addition to helping with food digestion, it creates essential vitamins and assists with training the immune system. This new research is the first to show a definitive connection with heritability.

Previous studies on the gut microbiome in humans showed only 5 to 13 percent of microbes were heritable, but Archie and the research team hypothesized the low number resulted from a “snapshot” approach to studying the gut microbiome: All prior studies only measured microbiomes at one point in time.

In their study, the researchers used fecal samples from 585 wild Amboseli baboons, typically with more than 20 samples per animal. Microbiome profiles from the samples showed variations in the baboons’ diets between wet and dry seasons. Collected samples included detailed information about the host, including known descendants, data on environmental conditions, social behavior, demography and group-level diet at the time of collection.

The research team found that 97 percent of microbiome traits, including overall diversity and the abundance of individual microbes, were significantly heritable. However, the percentage of heritability appears much lower — down to only 5 percent — when samples are tested from only a single point in time, as is done in humans. This emphasizes the significance of studying samples from the same host over time.

“This really suggests that in human work, part of the reason researchers haven’t found that heritability is because in humans they don’t have a decade and half of fecal samples in the freezer, and they don’t have all the initial host (individual) information they need to tease these details out,” said Archie.

The team did find evidence that environmental factors influence trait heritability in the gut microbiome. Microbiome heritability was typically 48 percent higher in the dry season than in the wet, which may be explained by the baboons’ more diverse diet during the rainy season. Heritability also increased with age, according to the study.

Because the research also showed the significant impact of environment on the gut microbiomes in baboons, their findings agreed with previous studies showing that environmental effects on the variation in the gut microbiome play a larger role than additive genetic effects. Combined with their discovery of the genetic component, the team plans to refine its understanding of the environmental factors involved.

But knowing that genes in the gut microbiome are heritable opens the door to identifying microbes in the future that are shaped by genetics. In the future, therapies could be tailored for people based on the genetic makeup of their gut microbiome.

The Amboseli Baboon Project, started in 1971, is one of the longest-running studies of wild primates in the world. Focused on the savannah baboon, the project is located in the Amboseli ecosystem of East Africa, north of Mount Kilimanjaro. Research teams have tracked hundreds of baboons in several social groups over the course of their entire lives. Researchers currently monitor around 300 animals, but have accumulated life history information on more than 1,500 animals.

The research was funded by the National Science Foundation.

In addition to Archie and former graduate student Laura Grieneisen, other authors include fellow principal investigators Ran Blekhman of the University of Minnesota and Jenny Tung of Duke University and the Canadian Institute for Advanced Research; Mauna Dasari, Johannes Björk and David Jansen of the University of Notre Dame; Trevor Gould of the University of Minnesota; Jean-Christophe Grenier, Vania Yotova and Luis B. Barreiro of Centre Hospitalier Universitaire Sainte-Justine Research Center; Neil Gottel and Jack Gilbert of the University of California, San Diego; Jacob B. Gordon, Laurence R. Gesquiere and Susan C. Alberts of Duke University; Niki H. Learn of Princeton University; and Tim L. Wango, Raphael S. Mututua, Kinyua Warutere and Long’ida Siodi of the Amboseli Research Project.

Contact: Jessica Sieff, assistant director of media relations, 574-631-3933, jsieff@nd.edu

Juniors Andrew Burke, Andrew Langford named 2021 Goldwater Scholars

2021-04-19T15:45:00-04:00

University of Notre Dame juniors Andrew Burke and Andrew Langford have been named Goldwater Scholars for the 2021-22 academic year.

Andrew Burke

Burke, of Stewartsville, New Jersey, is a mathematics honors major with a concentration in computing. He is a Glynn Family Honors Scholar.

Langford, of Avon, Indiana, is a physics honors major with concentrations in applied physics, astrophysics and advanced physics. He is a Flatley Center for Undergraduate Scholarly Engagement (CUSE) Sorin Scholar.

Named for former U.S. Sen. Barry Goldwater, the Goldwater Scholarship encourages outstanding sophomores and juniors to pursue careers in the fields of mathematics, the natural sciences and/or engineering. It covers tuition, fees, books and room and board up to $7,500 per year for one or two years.

“I was elated to receive the news and share it with my research advisers and family. I felt a great sense of appreciation for the support and mentorship I have received to get to this point,” Langford said.

In applying for the scholarship, Burke and Langford worked closely with Jenny Smith and Dan Gezelter. Smith is the undergraduate research adviser for CUSE. Gezelter is a professor of chemistry and biochemistry and associate dean for undergraduate studies in the College of Science, and the campus representative for the Goldwater Scholarship.

“These students represent the best of Notre Dame. The College of Science is immensely proud that their academic and research accomplishments have been recognized with this award,” Gezelter said.

Andrew Langford

Burke said he is thankful to the professors in the mathematics department, especially Emeritus Professor Francis Connolly, who helped him apply. Burke plans to seek a doctoral degree in mathematics after graduating from Notre Dame.

Langford also plans to enroll in a doctoral program after graduation. He would like to study the dynamics of multibody gravitational environments, and is interested in applying dynamical systems theory to spacecraft trajectory design and exoplanet detection techniques.

“Another successful year with multiple Goldwater recipients is a testament not only to these students’ outstanding talent and work ethic, but also to the strength of the STEM programs at Notre Dame that prepare students to reach exceptionally high achievements,” said Smith.

For more information on this and other scholarship opportunities, visit cuse.nd.edu.

Contact: Erin Blasko, assistant director of media relations, 574-631-4127, eblasko@nd.edu

Out of the “Shadow”

2021-04-12T09:00:00-04:00

When Dr. Matthew Molloy ’10 was a student at the University of Notre Dame, he knew he had to participate in some form of “job shadowing” where he followed a physician around for a day or more, asking questions and watching the doctor’s interaction with patients.

“I think those shadowing experiences can be so variable,” said Molloy, now a pediatric hospitalist at Cincinnati Children’s Hospital. “Some people can have an awesome shadowing experience, but I almost felt I was doing it a little to check a box.”

Most people who shadow can’t delve into how doctors think, and are exposed to only one type of medicine. Also, if a doctor had a busy day, it can be difficult to ask questions or get advice. In 2020, the practice came to a screeching halt anyway because of the COVID-19 pandemic.

To read the full story, click here.

Protein rewires metabolism to block cancer cell death, may allow cancer spread

2021-03-29T15:05:00-04:00

One specific protein may be a master regulator for changing how cancer cells consume nutrients from their environments, preventing cell death and increasing the likelihood the cancer could spread, a study from the University of Notre Dame has shown.

The study, published in Cell Reports, was completed in the laboratory of Zachary Schafer, the Coleman Foundation Associate Professor of Cancer Biology in the Department of Biological Sciences.

Schafer and collaborators found a protein called SGK1, known to be activated in a variety of cancer cell types, signals the cell to take up nutrients. These nutrients include glucose, which allows the cell to survive after it detaches from the scaffold of proteins it had been attached to, called the extracellular matrix. Non-cancerous cells often die after detaching from the extracellular matrix, but SGK1 activity promotes survival and therefore increases the chances that the cancer could spread, or metastasize.

“If you better understand precisely how cancer cells that are potentially metastatic survive in these sorts of foreign environments, then you can potentially antagonize those survival pathways and selectively cause those cells to die,” said Schafer, also an affiliate member of Notre Dame’s Harper Cancer Research Institute.

More than 90 percent of cancer deaths are caused by metastasis of cancer cells from one location to another, Schafer said. For instance, breast cancer can metastasize to the brain, and metastatic cancer cells need to adapt to the new environment there.

There are unique circumstances where the SGK1 protein is critically important, so there might be a vulnerability that researchers can target and alter the way the cells process their nutrients, said Schafer.

This discovery appears to be broadly relevant across many different types of cancer, Schafer said, with research in this paper focused on breast and colon cancer cells grown in cultures under different conditions. The research took place over a number of years, and in addition to a collaboration with the Duke University 91��Ƶ of Medicine and Northwestern University Feinberg 91��Ƶ of Medicine, several Notre Dame postdoctoral, graduate and undergraduate researchers assisted with the work.

The next step in the research is to complete a “proof of principle” study, which is an early-stage investigation of how this knowledge could be leveraged for clinical benefit. Such a study could reveal if different agents — which could become therapeutics — could potentially eliminate the cells in question.

“If you can kill those cells that are potentially metastatic, then potentially you can get to a point where you can block cancer dissemination,” Schafer said.

The study was funded by the American Cancer Society, the Phi Beta Psi National Project, the Coleman Foundation, the National Science Foundation (through a Research Experience for Undergraduate grant) and the Malanga Family Excellence Fund for Cancer Research.

Contact: Jessica Sieff, assistant director of media relations, 574-631-3933, jsieff@nd.edu

Three-part Zoom series on neuroscience and behavior launches in March

2021-03-15T11:45:00-04:00

How your brain works impacts not only your behavior, but also your worldview. Early environments and experiences affect the brain and overall health, research has shown.

“Neuroscience and (Your) Behavior: How your experiences shape your brain and your outlook” is the second program in the Notre Dame College of Science’s series of multimedia educational enrichment programs — called The Science Lab — for The Alumni Association’s ThinkND.

The online, synchronous programs will be held from 11:30 a.m. to 12:30 p.m. on March 18 and 25 and April 1, and will be led by Nancy Michael, associate teaching professor and director of undergraduate studies for Neuroscience and Behavior.

Negative early relationships and stressors wire our brains in physical ways that researchers have determined can lead to diagnoses such as depression, anxiety, addiction and even cancer, diabetes and heart disease. However, positive experiences can lead to resilience and improved overall health. The study of neuroscience and behavior offers deep insight into understanding our own thinking and how we engage with others. This self-awareness can ultimately encourage us to consider our responsibility in meeting others in dignity and solidarity.

Questions about people and behavior led Michael to study neuroscience in graduate school, she said.

“Everything I've learned since has changed how I see and engage with the world around me; the way I teach, parent, talk to the cashier at the store and even care for myself. By developing our understanding of our brains and how experiences shape our brain and behavior, we are offered a deeper understanding of ourselves,” she said.

“From this perspective we can earnestly engage with the Mission our Lady's University of using our education in service to justice no matter our vocational calling.”

“Neuroscience and (Your) Behavior” includes short explainer videos, optional readings and interactive, one-hour Zoom sessions. The program, which launches during Women’s History Month, includes mostly female guests, including Kristin Valentino, director of the William J. Shaw Center for Children and Families and the William J. Shaw Center for Children and Families Professor of Psychology; Elizabeth Archie, associate professor in the Department of Biological Sciences; Connie Snyder Mick, director of academic affairs for the Center for Social Concerns and director of the poverty studies minor; and Kimberly Green Reeves, director of community health and community benefit at Beacon Health System.

The sessions are free and open to the public.

Originally published by Deanna Csomo McCool at science.nd.edu on Feb. 26.

Nancy Michael earns outreach award from the Society of Neuroscience

2020-11-20T11:00:00-05:00

Nancy Michael, associate teaching professor of neuroscience and behavior at the University of Notre Dame, earned a Next Generation Award from the Society for Neuroscience for her community-based learning programs and course for undergraduates that matches students with community partners that serve a vulnerable local population.

Michael, who is also the director of undergraduate studies for neuroscience and behavior, won the Next Generation outreach award for junior faculty.

“This award is meaningful, and I think about it not in the context of recognition, but in terms of the impact of the work I have done. The way I approach education and research is to think about how we might give opportunities for more stable communities,” she said. “I do the things I do because I want to be the best teacher and the best mentor, and leave the world in a little bit of a better place.”

She has developed neuroscience-based materials to meet the needs of undergraduate students, school districts and community organizations. In the developmental neuroscience course she designed and teaches, students are matched with a community partner serving a vulnerable local population, including Hannah’s House, the Robinson Community Learning Center and the South Bend Center for the Homeless.

In addition to her use of community-based learning with Notre Dame undergraduates, Michael has engaged with local schools in topics related to brain health. She has also taught juvenile detention officers and staff about how adverse childhood experiences and stress affect the developing brain.

Two others won the Next Generation awards for pre- and postdoctoral students and a professor at Duquesne University earned the organization’s Science Educator Award.

“The society is honored to recognize this year’s winners, whose efforts to inspire students of all ages, as well as adults and the general public, reflect a passion and enthusiasm for STEM outreach and health literacy,” Society for Neuroscience president Barry Everitt said. “In addition to conducting their own research in neuroscience, they have found creative ways to reach out to the larger community, and especially underserved populations, to instill an appreciation for brain science and health.”

Originally published by Deanna Csomo McCool at science.nd.edu on Oct. 29.

Phillips named fellow of National Society of Black Physicists

2020-11-16T14:30:00-05:00

L. Arielle Phillips, research assistant professor in the Department of Physics at the University of Notre Dame, has been named a fellow of the National Society of Black Physicists (NSBP).

She was primarily recognized for her work teaching an algebra-based physics program at Westville Correctional Facility through the Moreau College Initiative Physics Program, where students can obtain a degree from Holy Cross College. She was the only member elevated to fellow in 2020.

“This is an unexpected recognition of the work I have done,” Phillips said. “You know when you are working toward something that you will either make an impact that is felt, or an impact that is known, and you can get great satisfaction when your impact is felt even if it is not known ... but it is a pleasant development when your work is recognized.

“So I was honored to be recognized as a fellow. I am doing things here that will impact my students and my field, which was an impact that is felt — but then this happened.”

In introducing Phillips’ elevation, Stephon Alexander, president of the NSBP, praised her for the Westville program she has been involved with since 2014, in addition to her co-production of High Z, an international collaboration of scientists and artists. He noted that she fulfilled these roles while leading an active research program in theoretical astrophysics.

The physics course she teaches is part of a liberal arts program for which those who are incarcerated across Indiana can apply, and transfer to if accepted.

The program consists of three algebra-based courses (mechanics, physics of civilization and astronomy). After an anonymous benefactor generously provided funding, Phillips and her team launched labs housed at the facility to match each of these courses. Coursework was temporarily suspended this year because of COVID-19 restrictions.

Naturally, teaching in a prison setting is vastly different from teaching at a university. Lack of Wi-Fi and restrictions on what she and graduate students may bring into the facility — and the time it takes to have materials cleared for entry — have created their own challenges, Phillips said.

“In the beginning we tried to do something that was really makeshift. I would bring in a tub of physics equipment, but I always had to have two to three ideas, because some equipment would not work,” she said. “Bringing in items could change what time I would start class dramatically, because sometimes they were intaking new inmates, and you never knew what you would come across.” But her students were always waiting for her when she arrived, and worked with her to make the labs successful.

Supplies are now left at the prison, allowing for faster entry, she said.

She is proud that her work to educate prisoners was recognized by the NSBP, describing her elevation to fellow as an honor.

“I remember going to my first meeting, and enjoying the community. It is an organization that I respect so much,” she said.

She joins a cohort of NSBP fellows elevated in the past, including Sylvester James Gates, the Brown Theoretical Physics Center Director at Brown University and former member of President Barack Obama’s Council of Advisors on Science and Technology, and Hattie Carwell, a physicist with the U.S. Department of Energy and the International Atomic Energy Agency.

Michael Hildreth, interim dean of the College of Science at Notre Dame, said he has always appreciated Phillips’ attention to education, diversity and the underserved, and regards her as a leader in engagement and outreach.

“Our department and indeed our local and national communities are richer by virtue of her efforts,” Hildreth said.

Originally published by Deanna Csomo McCool at science.nd.edu on Nov. 12.

Cancer cells mediate immune suppression in the brain

2020-10-27T11:00:00-04:00

Scientists have long believed that the brain protects itself from an aggressive immune response to keep down inflammation. However, that evolutionary control may work against it when a cancer cell attempts to spread to the brain, researchers at the University of Notre Dame have discovered.

In newly published research in the journal Cell, researchers showed that one type of cell important for immunity, called a myeloid cell, can suppress the immune response — which has the effect of allowing breast cancer cells to metastasize to the brain to form secondary tumor cells there.

“We wanted to understand how the brain immune environment responds to the tumor, and there are so many different cells, and so many changes,” said Siyuan Zhang, the Dee Associate Professor in the Department of Biological Sciences, a researcher for Harper Cancer Research Institute and a co-author on the paper. “The traditional belief was that the process described in this paper would be anti-tumor, but in our case, after a lot of experimenting, we discovered it is a proponent of metastasis.”

Through single-cell sequencing — not powerful enough even a few years ago for this type of work — and an imaging technique, the researchers discovered that a myeloid cell type called microglia promoted the outgrowth of breast cancer that has spread to the brain by the expression of several proteins. The microglia release one protein — an immune cell-attracting protein called CXCL10 — to recruit more microglia to the metastasis. All these microglia express a protein named VISTA, which serves as protection against brain inflammation. But when faced with a cancer cell, this two-part process suppressed important T-cells. T-cells, which heighten the body’s immune response, would usually prevent the spread of cancer throughout the body.

The activation of the VISTA checkpoint had not previously been known as a potential promoter of brain metastasis, said the paper’s lead author, Ian Guldner, a graduate student in Zhang’s lab. In addition to using a mouse model for the research, the team used data mining techniques to validate how humans’ brains would respond.

Clinically, the discovery is relevant, because antibodies have been developed that blocked VISTA in humans, Guldner said. However, significant additional work needs to be performed to ensure the safe and effective use of VISTA-blocking antibodies in people with brain metastases.

Learning about the structures within cells in the brain will help researchers not only understand cancer, but also degenerative diseases such as Parkinson’s, multiple sclerosis and Alzheimer’s, Zhang said.

“The brain immune system is a very active field, since brain cells are dysregulated during the aging process,” Zhang said. “There is so much to learn.”

In addition to Guldner and Zhang, other collaborators include Qingfei Wang, Lin Yang, Samantha Golomb, Zhuo Zhao, Jacqueline A. Lopez, Abigail Brunory, Erin Howe, Yizhe Zhang, Bhavana Palakurthi, Martin Barron, Hongyu Gao, Xiaoling Xuei, Yunlong Liu, Jun Li, Danny Chen, all of Notre Dame, and Gary E. Landreth, part of the Indiana University 91��Ƶ of Medicine Stark Neurosciences Research Institute in Indianapolis. Zhang is also affiliated with the Indiana University Melvin and Bren Simon Comprehensive Cancer Center, also in Indianapolis.

The research was funded by three grants from the National Institutes of Health, a Notre Dame CRND Catalyst award and the Nancy Dee Family Endowment.

Contact: Jessica Sieff, assistant director of media relations, 574-631-3933, jsieff@nd.edu

Light pollution may increase biting behavior at night in Aedes aegypti mosquitoes

2020-10-20T15:35:00-04:00

Artificial light abnormally increases mosquito biting behavior at night in a species that typically prefers to bite people during the day, according to research from the University of Notre Dame that was published in The American Journal of Tropical Medicine and Hygiene.

Increased biting by Aedes aegypti mosquitoes, which normally fly and bite in the early morning and during the afternoon, highlights the concern that increasing levels of light pollution could impact transmission of diseases such as dengue fever, yellow fever, chikungunya and Zika.

“This is potentially a very valid problem that shouldn’t be overlooked,” said Giles Duffield, associate professor in the Department of Biological Sciences, who is also affiliated with the Eck Institute for Global Health and the Neuroscience and Behavior Program. Unlike other species that may emerge from the forest to feed on humans and animals, Aedes aegypti evolved with humans and prefers to feed on them.

“They live and breed in the vicinity of houses, so the chances of Aedes aegypti being exposed to light pollution are very likely,” he added.

To conduct the experiment, the study’s first author, Samuel S. C. Rund, a staff scientist in the Department of Biological Sciences, allowed mosquitoes in cages to bite his arms under controlled conditions, including during the day, at night or at night while exposed to artificial light. The female mosquitoes — the only ones that bite — were twice as likely to bite, or blood-feed, at night when they were exposed to artificial light. Twenty-nine percent of the mosquitoes in the control group, which had no light, fed at night, while 59 percent of the mosquitoes exposed to artificial light blood-fed.

The findings will help epidemiologists better understand the true risk of disease transmission by this species. The discovery could also lead to more recommendations for bed net use. Usually mosquito bed nets are used at night to ward off bites from a different genus of mosquitoes, Anopheles, but because Aedes aegypti were shown to be stimulated by artificial light, mosquito nets could also be used in areas with a likelihood of disease transmission even with limited Anopheles activity.

“The impact of this research could be huge, and it probably has been overlooked,” Duffield said. “Epidemiologists may want to take light pollution into account when predicting infection rates.”

Duffield and his collaborators plan to experiment with additional variables of artificial light to further study Aedes aegypti biting activity. These variables include the duration of light, its intensity and color, and the timing of the biting — whether early at night or later. The team is also interested in the molecular genetic pathways that might be involved with biting activity, after noticing that not every mosquito in the population under study was interested in biting at night even with artificial light.

“So, we think there is a genetic component within the Aedes aegypti species,” Duffield said.

In addition to Duffield and Rund, other authors include undergraduate students Laura F. Labb and Owen M. Benefiel, also from Notre Dame. The research was supported by the Eck Institute for Global Health, a University of Notre Dame College of Science Summer Undergraduate Research Fellowship and a contract from the National Institute of Allergy and Infectious Diseases.

Contact: Jessica Sieff, assistant director of media relations, 574-631-3933, jsieff@nd.edu

New College of Science, ThinkND multimedia series covers algorithms and ethics

2020-10-02T16:00:00-04:00

The famous saying “numbers don’t lie” might work when reporting the score of a football game, but even then, the numbers don’t tell the whole story.

Algorithms developed by data scientists have implications for not only who may obtain a fair loan, but who stays in prison and who’s released, and who will be favored by machine learning “decisions.” With so many parts of our lives decided by Big Data, how do scientists balance the algorithms and the ethics?

The University of Notre Dame College of Science and Notre Dame Alumni Association's ThinkND, along with partners from across the University, are launching The Science Lab, an open, multimedia educational enrichment program featuring Notre Dame’s world-class science researchers and other scientific leaders. The first in the series, "Numbers Can Lie: When algorithms work perfectly but fail miserably," will be held at noon Eastern time on three Fridays: Oct. 9, Oct. 23 and Nov. 6. Registration is open.

The program is led by Roger Woodard, the director of Notre Dame’s Online Master’s in Data Science program. In the three sessions of this program, listeners will learn the basics behind data science and discover how easily human bias can be encoded into computer models.

“This program is important to me because Notre Dame has a long tradition of fighting for the social good. That is why we focus not only on the rigorous technical side of data science, but also on the ethical side,” Woodard said. “Data science algorithms can streamline business processes, improve medical treatment and help us find the products we want.”

Many people assume that algorithms produce irrefutable facts and unbiased opinions, he noted. “But when it comes to data science we need to realize that algorithms can work perfectly from a technical point of view, but have a negative impact on the people around us. In this program we are going to explore how that can happen.”

Numbers Can Lie includes short explainer videos; a book selection, “Weapons of Math Destruction,” by Cathy O’Neil, who will speak at the third meeting; and interactive, one-hour Zoom sessions. The program is free and open to all, and is hosted exclusively on ThinkND, Notre Dame’s open, online learning community.

Other programs in The Science Lab will launch beginning early 2021.

“The process of doing science at Notre Dame has always been about building knowledge to impact society in positive ways,” said Mary Galvin, the William K. Warren Foundation Dean of the College of Science. “Perhaps now more than ever, performing scientific research is crucial to advancing society in ways that will help the most people in the best ways possible.”

The Alumni Association’s ThinkND synchronous learning series include several different areas of research and topics, and have become an essential part of connecting with the University and learning from home.

"As science and data continue to grow in prevalence and importance in our society, we are excited to work with our campus partners to bring The Science Lab to the Notre Dame family," said Dolly Duffy, executive director of the Alumni Association. "The partnership between ThinkND and the Notre Dame academic community continues to grow and provide outstanding learning opportunities for our alumni, parents and friends."

Originally published by Deanna Csomo McCool at science.nd.edu on Sept. 21.

Common cholesterol drugs could slow spread of breast cancer to brain

2020-06-16T12:00:00-04:00

A new study from the University of Notre Dame shows drugs used to treat high cholesterol could interfere with the way breast cancer cells adapt to the microenvironment in the brain, preventing the cancer from taking hold. Patients with breast cancer who experience this type of metastasis typically survive for only months after diagnosis.

Statins, a group of drugs commonly prescribed for those with high cholesterol, were shown to interfere with a pathway that allows a cancer cell to recycle cell surface proteins and therefore make it easier for cancer cells to live within the brain.

Siyuan Zhang

“It normally takes a decade to develop new medications. Instead of waiting, we can repurpose medications people are already taking,” said Siyuan Zhang, the Dee Associate Professor in the Department of Biological Sciences, and principal investigator of the study published in Nature Communications. “Statins are relatively safe drugs, and they can even be given, if doctors choose, to try to prevent metastasis.”

The protein Rab11b brings “recycled” proteins back to the surface like a fast-moving Ferris wheel, Zhang said. Statins suppress breast cancer survival in the brain by inhibiting the ability of Rab11b to recycle surface proteins. As a result of less recycling, the surface of metastatic tumor cells is less sticky. This limits the survival of cancer cells, and ultimately slows the rate of tumor colonization in the brain microenvironment.

To complete the research, Zhang’s lab completed gene profiling to screen for genes that were functionally important in inhibiting the way tumor cells adapted to the brain, Zhang said. Then, they used a fruit fly tumor model to perform a genetic tumor growth screen, allowing the team to quickly narrow down a subset of genes that might be important for tumor formation in the brain.

“We knew Rab11b sits downstream of an enzyme that is important for cholesterol synthesis, so once we recognized its role, we thought that statins could knock Rab11b back from its role in pushing the other proteins up to the surface in metastatic breast cancer in the brain,” said Zhang, who is affiliated with the Harper Cancer Research Institute.

Zhang’s lab seeks uses of already-FDA-approved drugs to target cancer metastasis because they are already known to be safe, which allows for quicker testing without waiting several years for new therapeutics to be developed and tested.

Collaborators on the study include lead author Erin Howe, a postdoctoral fellow in Zhang’s lab; Jeremiah J. Zartman, associate professor of chemical and biomolecular engineering, Crislyn D’Souza-Schorey, the Morris Pollard Professor in the Department of Biological Sciences, and Jun Li, associate professor in the Department of Applied and Computational Mathematics and Statistics at Notre Dame; Victoria Hedrick and Uma K. Aryal at Purdue University; former Notre Dame postdoctoral scholars Miranda Burnette, Patricia M. Schnepp, Ian Guldner, Alicia Lamere and James Clanc, and former undergraduate student Melanie Justice.

Funding for the project was provided through an Advancing Basic Cancer Research Grant from the Walther Cancer Foundation, the Department of Defense and the National Institutes of Health.

Contact: Jessica Sieff, assistant director of media relations, 574-631-3933, jsieff@nd.edu

Understand and Fight: Notre Dame researchers and the COVID-19 pandemic

2020-06-15T11:00:00-04:00

The hero in Mary Shelley’s “The Last Man,” her second sweeping political science fiction after “Frankenstein,” is left alone in Rome, in a post-apocalyptic world. A global plague apparently took the lives of everyone else, yet he discerns a duty to forge ahead, no matter what.

Published in 1826, the novel mirrored Shelley’s life as she despaired at the loss of several of her loved ones. Her sister Fanny died by suicide. Her husband, the poet Percy Bysshe Shelley, drowned after a sailing accident. She lost another friend, the poet Lord Byron, to infection. Two of her toddlers died — one of malaria, and another from a fever. She kept a kind of plague journal, according to Eileen Hunt Botting, a professor in the department of political science, “in order to fight fatalism.”

“She found the courage to persist by writing about the reasons why she had an obligation to continue in this world, and serve in this world, despite the tragedy,” says Botting, whose book, “Artificial Life after Frankenstein,” will be published later this year. “At the end of Shelley’s novel, we find this powerful image of the seemingly last surviving human looking for other survivors, even as he sometimes doubts he will find them.”

As Notre Dame’s laboratories went into hibernation in March, many researchers from various fields — chemistry, engineering, political science, psychology, education — looked for ways to pivot their own work toward furthering knowledge into how COVID-19, the disease caused by the SARS-CoV-2 virus, works, how it’s transmitted, and how our country and world can cope with the unexpected pandemic crisis. They decided to jump into the research at different times, but for the same reason: They knew they could help.

To read the story, click here.

In Memoriam: Clarence “Earl” Carter, assistant dean in the College of Science

2020-05-19T10:00:00-04:00

Clarence “Earl” Carter, 61, assistant dean for faculty affairs and special projects in the College of Science at the University of Notre Dame, died unexpectedly on Thursday, May 14, at his home.

After a long career in the United States Navy, Carter joined the University faculty in 2011 as a professor of naval science and commanding officer for the Naval Reserve Officer Training Corps Unit. He became an assistant dean in 2013, where he served in a chief of staff role for matters pertaining to the College of Science faculty. He coordinated special events and projects, and assisted in the college’s strategic planning. He served as interim managing director of the Notre Dame Haiti program from 2013 to 2015.

“Above all, Earl was a very kind and generous person who lived his faith,” said Mary Galvin, the William K. Warren Foundation Dean of the College of Science. “His compassion was evident through his interactions with faculty, staff and students, and he had a way of listening and advising that solved many problems and healed wounds.

“From my start at Notre Dame, I turned to Earl for guidance and advice. He made the college and all of us better, and will be forever missed.”

During his 32-year naval career, Carter was a submariner whose career highlights included serving as commanding officer of the nuclear-powered submarine USS Scranton, leading its crew on the first mission to the North Pole by a Los Angeles Class submarine, and later serving as commander of Submarine Squadron Eight, comprising 10 fast-attack submarines and their crews. Carter earned a number of medals, awards and commendations before retiring in 2012.

In his role as assistant dean, Carter worked closely with the Notre Dame Office of the Provost, including Christine Maziar, vice president and senior associate provost for budget and planning. As an academic administrator, Carter wore several hats and switched gears often, which he did with ease, Maziar said.

“You don’t carry ‘special projects’ in your title without being that special kind of person who can be assigned some of the toughest, often irregular, and sometimes off-the-wall assignments without complaint, and Earl was one of those special people,” Maziar said.

He was also an advocate who worked tirelessly for the Notre Dame Haiti Program, which has culminated in the Bon Sel Dayiti Salt Project. The project fortifies salt to reduce iodine deficiencies and to eliminate lymphatic filariasis, a disease of the immune system that causes swelling of the limbs, breasts and genitals and is a leading cause of disability in the world.

He was completely committed to health and welfare of the people of Haiti, according to volunteer David O’Brien, who said, “He deeply believed he was serving Christ through our work.”

In addition, Carter was involved with the Ara Parseghian Medical Research Fund, which is dedicated to funding medical research projects to find a treatment for Niemann-Pick Type C disease. He often assisted with the yearly golf outing, the Parseghian Classic in Pebble Beach, California. The outing is a major fundraising event for the organization.

Carter is survived by his wife, Lea; his two daughters, Alora and Ciera; a son, Joseph; and his sister, Kathryn Carter.

Visitation will take place from 4 to 7 p.m. Wednesday, May 27, at Grace Church, 52025 Gumwood Road, Granger. Funeral services will take place at 2 p.m. Thursday, May 28, at Grace Church. Burial will take place at a later date at Arlington National Cemetery.

Contributions in his memory may be made to Boy Scouts of America, LaSalle Council #165, 1340 South Bend Ave., South Bend, IN 46617, or Grace Church, 52025 Gumwood Road, Granger, IN 46530. They may also be made to the Haiti Salt Program online at giving.nd.edu, by phone at 574-631-5150, or by mail to University of Notre Dame, Department of Development, 1100 Grace Hall, Notre Dame, IN 46556.

Notre Dame’s Nora Besansky elected to National Academy of Sciences

2020-05-04T08:25:00-04:00

Nora J. Besansky, the O’Hara Professor in the Department of Biological Sciences at the University of Notre Dame, has been elected to membership in the National Academy of Sciences.

Besansky, an expert in the genomics of malaria vectors, has applied several genomic technologies to deepen the understanding of the relationship between malaria-transmitting mosquitoes and their environments. Research in her laboratory has been aimed at uncovering how two genetic processes — chromosome structural rearrangements known as inversions, and the transfer of genes between species known as introgression — contribute to enhanced ability to transmit disease.

She is currently working on developing novel genomic resources and tools, including molecular inversion genotyping, to further her research.

“Professor Besansky is a distinguished scientist whose research into the genomics of malaria vectors has provided profound contributions to the field of vector biology,” said Mary Galvin, the William K. Warren Foundation Dean of the College of Science. “Induction into the National Academy of Sciences is one of the highest honors a scientist can receive, and we in the College of Science are very proud of Nora for not only this distinction, but also for her significant research achievements.”

Her research focuses on groups of closely related related Anopheles species — species so closely related that they cannot be differentiated under a microscope — to determine what allows some of them to thrive and spread disease efficiently, while others play no role, or only a minor role, in disease transmission. A key to this puzzle is “ecological plasticity,” which allows the mosquitoes to thrive and be efficient vectors in a wide variety of environments, whether they are found in rainforests or in semi-deserts.

Fully understanding the evolutionary, ecological and functional genomics of malaria vectors will allow scientists to develop new control strategies that can interrupt transmission of the disease. Public health success against malaria has long been fragile because mosquitoes quickly develop resistance to insecticides, and the primary tool to stop the spread of the disease has been the bed net, which by itself is not sufficient to interrupt transmission.

“Through her many years of research into the genomics of malaria, Nora has had a tremendous impact on the field and significantly advanced our University’s pioneering efforts into vector-borne infectious diseases,” said Thomas G. Burish, the Charles and Jill Fischer Provost at Notre Dame. “We are thrilled to see her work recognized with this well-deserved honor.”

Besansky said she was shocked when she received the phone call telling her she was elected into the NAS.

“My first thought was one of disbelief,” she said. “My second thought was gratitude for my numerous students, trainees, mentors, collaborators and support team, without whom this would have been impossible.

“And the third thought is a feeling of great responsibility, given the mission that the NAS is charged with. It’s a great opportunity for me. I will be in the company of giants — with people I never thought I would rub shoulders with.”

Besansky earned her doctoral degree from Yale University in 1990, after earning her bachelor’s degree in biology from Oberlin College. She worked as a postdoctoral research fellow for the Centers for Disease Control, and was a staff scientist at the CDC from 1991 to 1997, during which time she also worked as an adjunct assistant professor in the Department of Biology at Emory University. She was hired as an associate professor in the Department of Biology at Notre Dame in 1997. In 2002 she was promoted to full professor, and became the O’Hara Professor in 2010. She is affiliated with Notre Dame’s Eck Institute for Global Health.

From 2005 to 2015, Besansky coordinated two large international genome sequencing and analysis projects sponsored by the National Institutes of Health (NIH), making genomic resources available to the scientific community for more than 16 malaria vector species. She was named a fellow of the American Association for the Advancement of Science in 2005, the American Society for Tropical Medicine and Hygiene in 2014, the Royal Entomological Society in 2016 and the Entomological Society of America in 2017. She has published more than 140 papers and mentored 30 graduate students and postdoctoral fellows. In addition to the NIH, her research has received support from the World Health Organization and the Bill & Melinda Gates Foundation.

Besansky is one of 120 members and 26 international members elected into the NAS for 2020, bringing the total number of active members to 2,403 and the number of international members to 501.

“It is not an exaggeration to say that the insights from her work will have a profound impact on the implementation and management of malaria control strategies,” said Crislyn D’Souza-Schorey, the Morris Pollard Professor and Chair of the Department of Biological Sciences at Notre Dame. “My colleagues and I are both delighted and proud to see Nora’s outstanding contributions recognized by her election to the NAS.”

Originally published by Deanna Csomo McCool at science.nd.edu on May 1.

Notre Dame physicists see nuclear wobbling in one isotope of gold

2020-02-18T10:00:00-05:00

Nuclei can be round, like a soccer ball, or oblong, like a football. Others are slightly oblong but misshapen, like a potato. One of the only two ways to observe the third shape, rarely encountered, is when the nucleus wobbles like a lopsided top.

Researchers had previously seen these rare triaxial nuclei wobble on their shorter, transverse axes. But University of Notre Dame researchers and collaborators recently discovered that the nuclei also wobble on their intermediate axes. Their research, “Longitudinal Wobbling Motion in ¹⁸⁷Au,” was published recently in the premier physics journal, Physical Review Letters.

The work took four to five days to complete once the team assembled at Argonne National Laboratory, in Illinois. Notre Dame physics graduate student, Nirupama Sensharma, who was the first author on the paper, spent about a year analyzing the data. Her work was highlighted recently in Nature.

Sensharma worked with Umesh Garg, professor in the Department of Physics, to develop an experiment using an isotope of gold to find out if the nucleus wobbled as predicted in a theoretical model developed by Stefan Frauendorf, also a professor in the Department of Physics. Frauendorf had hypothesized that triaxial nuclei would have two different types of wobbling motion.

The fundamental research, which Garg said does not have an immediate application for technology, was chosen as an editor’s selection in the journal. It was also highlighted as a synopsis in Physics, the online magazine of the American Physical Society. Papers selected for coverage must include an experimental breakthrough, or provide a theory with a new perspective, among other criteria.

“Where its importance lies is in confirming the predictive power of the underlying theoretical framework, generating more confidence in other predictions about nuclear physics,” Garg said. “This, among other things, can help us understand how various processes happen in stellar environments, and how heavy elements, like gold, are formed in the universe.”

Stefan Frauendorf

In 2016 Frauendorf suggested an experiment on a gold nucleus after predicting the wobbling should exist.

“Professor Garg’s group created an outstanding experiment to measure the distribution of radiation,” Frauendorf said, noting that the experiment validated his prediction.

The work, funded by the U.S. Department of Energy, was completed at the Argonne National Laboratory inside an instrument called Gammasphere. Gammasphere is the world’s most powerful gamma ray spectrometer, and collects gamma ray data following the fusion of heavy ions. Inside Gammasphere, a beam of ions and the target nucleus combine to create a much heavier, highly excited nucleus that gives off gamma rays. By observing the pattern and properties of the gamma rays, researchers can discover the structure of the nucleus – and a wobbling nucleus has a very specific structure.

Initially, Garg and his collaborators planned to look for wobbling in ¹⁸⁹Au, but ended up accidentally populating another isotope of gold, ¹⁸⁷Au, more strongly. The mistake was a serendipitous one.

“That one was right, it turns out,” Garg said. “But that’s how science goes; if we had done the experiment exactly as planned, I probably would have come back and said, this doesn’t very much seem like what we’re looking for.”

In addition to researchers from Notre Dame and Argonne National Laboratory, in Lemont, Illinois, other collaborators include scientists from Technische Universitat Munchen, Garching, Germany; the United States Naval Academy, University of North Carolina Chapel Hill, Duke University, University of Maryland, the Consortium for Scientific Research, Kolkata, India, and the Tata Institute of Fundamental Research, Mumbai, India.

Originally published by Deanna Csomo McCool at science.nd.edu on February 05, 2020.

University of Notre Dame-developed home lead screening kits shown to be highly accurate

2020-02-13T11:00:00-05:00

An inexpensive lead sample collection kit distributed to homes in St. Joseph County is comparable in accuracy and sensitivity to more costly in-home analysis, according to research published this month in the Journal of Environmental Research.

The Notre Dame Lead Innovation Team (ND LIT), central to the research, began its focus in 2016 to uncover hidden lead threats in homes before children are poisoned from their environments. The team is ready to take the next step toward distributing the screening kits for eventual nationwide use.

“Folks don’t have an inexpensive or quick method to test for lead,” said Heidi Beidinger-Burnett, assistant professor in the Department of Biological Sciences. “You have to call the health department, and it takes weeks to complete the entire process. Or if you have some money, it’s $200 to $300 to have a private risk assessor come out to your house.”

With the kit developed at Notre Dame — which costs about $10 to manufacture — people can have results within a week, and are given do-it-yourself strategies to mitigate lead risks in their homes, Beidinger-Burnett said. The kit contains tools to collect samples from paint, soil and dust, and was distributed to 45 households during the summer of 2018 to screen homes for lead exposure risks.

Researchers observed how homeowners used the kit to collect three soil samples, two paint samples and three dust samples from inside and around their homes, according to the study. The team analyzed data in the laboratory of Marya Lieberman, professor in the Department of Chemistry and Biochemistry, using a portable X-ray fluorescence (XRF) spectrometer and compared those results with results from in-home XRF analysis.

The study showed the kits to be accurate about 96 percent of the time. Results also showed that the kit was both sensitive and specific, meaning that it identified samples that were above EPA thresholds as leaded, and didn’t “cry wolf” by identifying non-leaded samples as leaded.

Paint chips were the only samples in which the lead testing kit was less sensitive than the in-home analysis. Because samples were collected using a card with double-sided tape, the tape sometimes retrieved only a small sample, or an oddly shaped paint chip, that didn’t encompass the whole beam area of the lab’s instrument. The team has since solved the problem by reporting the result as an “insufficient sample” if the paint chip is not large enough.

“The benefits to this country — and globally — of an inexpensive lead screening kit are huge,” said Meghanne Tighe, lead author on the study and a third-year graduate student in the Lieberman and Peaslee laboratories.

In addition to Lieberman and Beidinger-Burnett, who are both affiliated with the Eck Institute for Global Health, and several graduate students, other members of ND LIT include Graham Peaslee, professor in the Department of Physics, Matthew Sisk, assistant librarian and Geographic Information Systems specialist for Hesburgh Libraries and Chris Knaub, Project Manager.

With plans to scale up the number of kits in use, the team is seeking manufacturing partners and exploring distribution methods. The researchers have built an inexpensive automated system that can analyze the samples. The automated XRF system, which can run hundreds of samples per day, can be replicated and installed in labs throughout the country, Tighe said.

Contact: Jessica Sieff, assistant director of media relations, 574-631-3933, jsieff@nd.edu

Study: Transmission of river blindness may be reduced when vegetation is removed

2019-11-25T10:40:00-05:00

The World Health Organization has set a goal to eliminate river blindness, a neglected tropical disease found mostly in African villages near fast-flowing rivers and streams, by 2030. Spread by bites from black flies that deposit a parasitic worm under the skin, the disease can cause itching and skin infections in addition to blindness.

Current approaches to reduce transmission of river blindness include treating those rivers and streams with pesticides, as well as providing drug therapy, but neither method has come close to ending transmission of the disease.

In a new study, a University of Notre Dame research team used mathematical modeling, which showed combining mass drug distribution with removing vegetation may be the quickest way to curb transmission.

Edwin Michael

“Modeling is a powerful tool to synthesize myriad information about parasite transmission,” said lead author Edwin Michael, professor in the Department of Biological Sciences at Notre Dame. “Once we obtain a working model, we have the capability to do forecasting into the future, and we can also use the available short-term, limited data to present decision makers with new information that is not otherwise available.”

Removing vegetation trailing in fast-flowing water bodies and throwing it onto riverbanks kills the black fly larvae, according to the study’s findings. This form of vector control, called “slash and clear,” was tried briefly during the 1960s and found effective, but wasn’t continued. The study, published in Nature’s Scientific Reports, includes modeling after a one-year field trial where researchers lived in villages in Uganda and worked with residents to test the process and earn their buy-in.

“All you need are machetes, and the activity is well-accepted by the community,” said Michael, who is affiliated with the Eck Institute for Global Health. “And there’s no cost involved.”

The group’s modeling work synthesized the information from the trial data and forecast the outcomes of the intervention into the future in different locations. The approach allowed researchers to understand how slash-and-clear impacts extinction of both black flies and worm infection in humans, and showed that the method worked well even when performed just once per year during the first month of the rainy season.

The slash-and-burn approach, because it is community-based and is free, can be more sustainable than using pesticides because the latter relies on governments to complete dosing rivers in a timely fashion, and costs money. It is also a feasible addition to administering drugs that kill the worm. The drugs can take many years to interrupt transmission, because adult worms can live for up to 15 years in the body.

The next step in the research is to develop further testing in the field, but Michael stressed that mathematical modeling can save some of the time and effort that would normally be used for conducting such empirical studies.

“When new data come in, you use it to further refine the model to reduce prediction uncertainty,” he said.

In addition to Michael, other collaborators include Morgan E. Smith and Shakir Bilal of the University of Notre Dame; Peace Habomugisha and Edson Byamukama of the Carter Center, Kampala, Uganda; Thomson L. Lakwo and Edridah Tukahebwa of the Ministry of Health, Kampala, Uganda; Moses N. Katabarwa and Frank O. Richards of Emory University and the Carter Center, Atlanta, Georgia; Eddie W. Cupp of Auburn University, Auburn, Alabama; and Thomas R. Unnasch of the University of South Florida, Tampa, Florida.

The study was supported by a grant from the National Institute of Allergy and Infectious Diseases and by fellowship funding through Notre Dame’s Eck Institute for Global Health.

Contact: Jessica Sieff, assistant director of media relations, 574-631-3933, jsieff@nd.edu

Researchers land funding to help launch diabetic ulcer drug over ‘Valley of Death’

2019-10-07T09:00:00-04:00

Thousands of new chemical structures are tested in hopes of discovering a single drug meant to treat a single disease. Of the 5,000 to 10,000 that are prepared, only about 250 of those make it to the pre-clinical stage, and potentially as few as five make it to clinical trials in humans.

The gap between discovery and clinical research is dubbed the Valley of Death — the place where promising compounds languish because of lack of funding in academic labs and start-up companies. But one compound developed at the University of Notre Dame recently received funding from the Department of Defense for this pre-clinical phase, allowing the drug to move beyond discovery and toward clinical trials in humans.

The compound, called (R)-ND-336, is a topical gel for treatment of diabetic foot ulcers. It was developed by Mayland Chang, research professor in the Department of Chemistry and Biochemistry, and Shahriar Mobashery, the Navari Family Professor in Life Sciences in the Department of Chemistry and Biochemistry. Both are affiliated with Advanced Diagnostics & Therapeutics and the Warren Family Research Center for Drug Discovery and Development.

About 25 percent of all patients with diabetes will develop foot ulcers. Elevated blood glucose causes numbness in the extremities, and the patients cannot feel the ulcers forming. They are notoriously difficult to heal.

The $4.6 million award from the Department of Defense will help fund the expensive studies required before the compound can be given approval by the FDA to be tested on people. Chang and Mobashery expect this pre-clinical phase to last two years, and both anticipate the compound to move ahead to human trials. Additionally, they have shown that it should not cause cancer or have other toxic side effects.

“Many times what happens is some drugs go into the market and pharmaceutical companies may just know that it works in humans, but they don’t really know how,” Chang said. “But we took a very systematic approach to address these issues.”

They evaluated the effectiveness of becaplermin, the only FDA-approved drug on the market to treat diabetic ulcers, which was introduced 20 years ago. It uses a growth factor to stimulate tissue healing and is moderately effective, but comes with a black box warning for an increase in cancer and death. They compared its effectiveness with (R)-ND-336 in diabetic mice, and showed that (R)-ND-336 was more effective.

Chang and Mobashery looked at the specific enzymes, called matrix metalloproteinases (MMPs), involved in remodeling tissues, and discovered that two closely related MMPs played roles in diabetic wound healing. One of the enzymes, MMP-9, slows healing, while the other one, MMP-8, promotes it. Therefore, broad-spectrum drugs that inhibit both of these MMPs would actually prevent the wound from healing by blocking MMP-8’s healing properties. (R)-ND-336 inhibits only MMP-9, preserving the beneficial effects of MMP-8. This makes it a superior drug in diabetic wound healing.

“We synthesized hundreds of inhibitors with different selectivity, and tested these compounds to figure out which one works better,” Chang said. “We found (R)-ND-336 is the best.”

They tested the presence of the target MMP-9 enzyme by collecting wound tissue that patients from Elkhart General Hospital donated for research. Chang and Mobashery determined that the most severe and infected wounds had higher levels of this detrimental enzyme, an observation that underscores the likely success in the future human trials.

Mobashery expects the latest funding will take them over the so-called Valley of Death, but more funds will need to be raised for the compound to undergo the first round of clinical trials.

Contact: Jessica Sieff, assistant director of media relations, 574-631-3933, jsieff@nd.edu

Biology professor receives NIH New Innovator Award to study the nervous system

2019-10-02T10:00:00-04:00

Cody Smith, a researcher in the University of Notre Dame’s Department of Biological Sciences, has been granted a highly competitive National Institutes of Health Director’s New Innovator Award that will allow him to perform bold research that has the potential to impact a broad area of science.

The award, established in 2007, supports unusually innovative research from early-career investigators who are within 10 years of their final degree or clinical residency. Smith, the Elizabeth and Michael Gallagher Assistant Professor of Biological Sciences, is among 60 early-stage innovators to have received the honor this year.

Smith’s research will focus on the study of glial cells, which are non-neuronal cells in the central and peripheral nervous systems. The $1.5 million he received provides him freedom to develop any type of experiment over five years that advances the understanding of how the diversity of glial cells contributes to the function of the nervous system.

“I am grateful and humbled for the opportunity to be selected for this New Innovator Award,” Smith said. “Even though my name is on the award, it is really the exceptional hard work and talent of the people in my lab that provided this opportunity. I am excited to see what we can discover together.”

Smith is the third professor from Notre Dame to receive the New Innovator Award. Shaun Lee, the Monahan Family Associate Professor of Rare and Neglected Diseases in the Department of Biological Sciences, and Rebecca Wingert, the Elizabeth and Michael Gallagher Associate Professor of Biological Sciences, both received the award in 2011.

“The NIH Innovator Award supports exceptionally creative, innovative, high-impact projects. We had two such awards in the department previously and now Cody Smith has brought us yet another. It is testament to the quality and prowess of our junior faculty,” said Crislyn D’Souza Schorey, the Morris Pollard Professor and Chair in the Department of Biological Sciences. “I am immensely proud of their accomplishments and the remarkable ways in which they contribute to the University's mission.”

Smith graduated with a bachelor of science in biology from Mercyhurst University, and earned his doctoral degree in cell and developmental biology from Vanderbilt University in 2012. He was a postdoctoral fellow at the University of Virginia until 2016, when he was hired at Notre Dame. In 2017, he was named the Alfred P. Sloan Fellow of Neuroscience, another prestigious award given to the next generation of scientific leaders.

In addition to the New Innovator Award, Cody was awarded a two-year, $80,000 grant from the Indiana Department of Health to study brain and spinal cord injuries. Specifically, his research will try to understand how nerves regenerate after spinal cord avulsions.

Contact: Jessica Sieff, assistant director of media relations, 574-631-3933, jsieff@nd.edu