It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Saturday, April 27, 2024
Research expo highlights student and faculty creativity
Event helped connect UTA inventors and entrepreneurs to leading business minds
UNIVERSITY OF TEXAS AT ARLINGTON
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EXHIBITORS AT THE UT ARLINGTON RESEARCH AND INNOVATION EXPO
Hundreds of faculty, students and business leaders flocked to The University of Texas at Arlington for its second annual Research and Innovation Expo, an event designed to showcase the University’s research efforts.
“This is an event where we can showcase our research achievements and encourage everyone to learn about and engage with other investigators outside their own fields,” said Eileen Clements, interim executive director of the UT Arlington Research Institute and an organizer of the event.
Researchers learned how to find external funding for their projects from such varied sources as federally funded government organizations like the National Science Foundation and National Institutes of Health, private foundations, or industry leaders who need technology solutions to advance their companies.
“This expo was a way for researchers who have been successful in securing extramural funding to offer advice to others,” said Jeff Campbell, director of the Shimadzu Institute for Research Technology at UTA and an event organizer. “We put together a cross-section of faculty from around campus to share their success stories and offer tips for future collaborations.”
“It’s all about the mindset,” Corson said. “Anyone on campus has it within them to embrace their entrepreneurial aspirations and get engaged, whether it’s an artist who is going out for their first gig or someone curing cancer.”
In addition to showcasing the talented faculty on campus in Arlington, the expo also featured business and entrepreneurial leaders from the community who offered their wisdom and words of motivation to the next generation of leaders.
“We need to be able to stay ahead of the curve by utilizing technology and innovation,” said attendee and speaker Troy Alley Jr., chief operating officer and president of real estate at Con-Real LP, the largest Black-owned construction and real estate company of its kind in the southern United States. “This is what helps you stay competitive.”
Panel at the UT Arlington Research and Innovation Expo
CREDIT
Photo courtesy UT Arlington
The expo was a platform for top private-sector, philanthropic and academic leaders from across the county to share lessons learned from their entrepreneurial experiences and advise UTA faculty. Additional guest speakers included:
Kirk Ririe, co-founder of Idaho Technology
Azad Madni, professor at the University of Southern California, member of the National Academy of Engineering and recipient of the Gordon Prize for Innovation in Engineering and Technology Education
Thom Ruhe, president and CEO of NC IDEA
Brian Kelsey, manager for economic development advisory services at EY
New circuit boards can be repeatedly recycled
UNIVERSITY OF WASHINGTON
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A TEAM LED BY RESEARCHERS AT THE UNIVERSITY OF WASHINGTON DEVELOPED A NEW PCB THAT PERFORMS ON PAR WITH TRADITIONAL MATERIALS AND CAN BE RECYCLED REPEATEDLY WITH NEGLIGIBLE MATERIAL LOSS. RESEARCHERS USED A SOLVENT THAT TRANSFORMS A TYPE OF VITRIMER — A CUTTING-EDGE CLASS OF POLYMER — INTO A JELLY-LIKE SUBSTANCE WITHOUT DAMAGE, ALLOWING SOLID COMPONENTS TO BE PLUCKED OUT FOR REUSE OR RECYCLING. HERE, FROM LEFT TO RIGHT IS A VITRIMER-BASED CIRCUIT BOARD, A SHEET OF GLASS FIBERS, VITRIMER THAT’S BEEN SWOLLEN AND REMOVED FROM A BOARD, AND ELECTRICAL COMPONENTS SUCH AS A COMPUTER CHIP.
A recent United Nations report found that the world generated 137 billion pounds of electronic waste in 2022, an 82% increase from 2010. Yet less than a quarter of 2022’s e-waste was recycled. While many things impede a sustainable afterlife for electronics, one is that we don’t have systems at scale to recycle the printed circuit boards (PCBs) found in nearly all electronic devices.
PCBs — which house and interconnect chips, transistors and other components — typically consist of layers of thin glass fiber sheets coated in hard plastic and laminated together with copper. That plastic can’t easily be separated from the glass, so PCBs often pile up in landfills, where their chemicals can seep into the environment. Or they’re burned to extract their electronics’ valuable metals like gold and copper. This burning, often undertaken in developing nations, is wasteful and can be toxic — especially for those doing the work without proper protections.
A team led by researchers at the University of Washington developed a new PCB that performs on par with traditional materials and can be recycled repeatedly with negligible material loss. Researchers used a solvent that transforms a type of vitrimer — a cutting-edge class of sustainable polymers — to a jelly-like substance without damaging it, allowing the solid components to be plucked out for reuse or recycling.
The vitrimer jelly can then be repeatedly used to make new, high-quality PCBs, unlike conventional plastics that degrade significantly with each recycling. With these “vPCBs” (vitrimer printed circuit boards), researchers recovered 98% of the vitrimer and 100% of the glass fiber, as well as 91% of the solvent used for recycling.
The researchers published their findings April 26 in Nature Sustainability.
“PCBs make up a pretty large fraction of the mass and volume of electronic waste,” said co-senior author Vikram Iyer, a UW assistant professor in the Paul G. Allen School of Computer Science & Engineering. “They’re constructed to be fireproof and chemical-proof, which is great in terms of making them very robust. But that also makes them basically impossible to recycle. Here, we created a new material formulation that has the electrical properties comparable to conventional PCBs as well as a process to recycle them repeatedly.”
Vitrimers are a class of polymers first developed in 2015. When exposed to certain conditions, such as heat above a specific temperature, their molecules can rearrange and form new bonds. This makes them both “healable” (a bent PCB could be straightened, for instance) and highly recyclable.
“On a molecular level, polymers are kind of like spaghetti noodles, which wrap and get compacted,” said co-senior author Aniruddh Vashisth, a UW assistant professor in the mechanical engineering department. “But vitrimers are distinct because the molecules that make up each noodle can unlink and relink. It’s almost like each piece of spaghetti is made of small Legos.”
The team’s process to create the vPCB deviated only slightly from those used for PCBs. Conventionally, semi-cured PCB layers are held in cool, dry conditions where they have a limited shelf life before they’re laminated in a heat press. Because vitrimers can form new bonds, researchers laminated fully cured vPCB layers. The researchers found that to recycle the vPCBs they could immerse the material in an organic solvent that has a relatively low boiling point. This swelled the vPCB’s plastic without damaging the glass sheets and electronic components, letting the researchers extract these for reuse.
This process allows for several paths to more sustainable, circular PCB lifecycles. Damaged circuit boards, such those with cracks or warping, can in some cases be repaired. If they aren’t repaired, they can be separated from their electronic components. Those components can then be recycled or reused, while the vitrimer and glass fibers can get recycled into new vPCBs.
The team tested its vPCB for strength and electrical properties, and found that it performed comparable to the most common PCB material (FR-4). Vashisth and co-author Bichlien H. Nguyen, a principal researcher at Microsoft Research and an affiliate assistant professor in the Allen School, are now using artificial intelligence to explore new vitrimer formulations for different uses.
Producing vPCBs wouldn’t entail major changes to manufacturing processes.
“The nice thing is that a lot of industries — such as aerospace, automotive and even electronics — already have processing set up for the sorts of two-part epoxies that we use here,” said lead author Zhihan Zhang, a UW doctoral student in the Allen School.
The team analyzed the environmental impact and found recycled vPCBs could entail a 48% reduction in global warming potential and an 81% reduction in carcinogenic emissions compared to traditional PCBs. While this work presents a technology solution, the team notes that a significant hurdle to recycling vPCBs at scale would be creating systems and incentives to gather e-waste so it can be recycled.
“For real implementation of these systems, there needs to be cost parity and strong governmental regulations in place,” said Nguyen. “Moving forward, we need to design and optimize materials with sustainability metrics as a first principle.”
Additional co-authors include Agni K. Biswal, a UW postdoctoral scholar in the mechanical engineering department; Ankush Nandi, a UW doctoral student in the mechanical engineering department; Kali Frost, a senior applied scientist at Microsoft Research; Jake A. Smith, a senior researcher at Microsoft Research and an affiliate researcher in the Allen School; and Shwetak Patel, a UW professor in the Allen School and the electrical and computer engineering department. This research is funded by the Microsoft Climate Research Initiative, an Amazon Research Award and the Google Research Scholar Program. Zhang was supported by the UW Clean Energy Institute Graduate Fellowship.
The number of health care professionals able to write a prescription for a key medication to treat addiction quadrupled at community health clinics from 2016 to 2021, according to a new study by researchers at Oregon Health & Science University.
The findings, published online today in the journal JAMA Health Forum, provides a glimmer of hope amid a national overdose epidemic that has claimed more than 100,000 lives in the United States in each of the past few years.
The study examined community health centers serving low-income people primarily in West Coast states. Researchers found the number of health care professionals prescribing buprenorphine increased from 8.9% to 37.5% from 2016 to 2021 — a substantial increase that researchers attribute to increased state and federal efforts to ease the ability of clinicians to prescribe medication to treat addiction.
Buprenorphine, approved by the Food and Drug Administration in 2002, relieves withdrawal symptoms, cravings and pain. It normalizes brain function by acting on the same target in the brain as opioids or heroin. It’s one of three medicines approved by the FDA for treatment of opioid dependence, along with methadone and naltrexone.
“It’s heartening,” said lead author Daniel Hartung, Pharm.D., M.P.H., associate professor in the OHSU-Oregon State University College of Pharmacy. “Over a third of the providers in these community health centers are writing prescriptions for buprenorphine.”
Researchers examined data from 166 clinics in the network supported by Portland-based OCHIN, Inc. The study included more than 1,300 health care professionals that provided care for some 570,000 people in 2021.
In clinics in rural areas, the proportion of health care professionals able to prescribe buprenorphine was even greater, growing from 20.3% to 52.7% in five years.
“There’s still a lot of work to be done,” Hartung said. “But it’s a step in the right direction when more providers have the capacity to write prescriptions to treat patients who want to be treated.”
In addition to Hartung, co-authors included Robert W. Voss, M.S., of OCHIN, Inc.; Steffani R. Bailey, Ph.D., and Nathalie Huguet, Ph.D., associate professors of family medicine in the OHSU School of Medicine; and John Muench, M.D., M.P.H., professor emeritus of family medicine in the OHSU School of Medicine.
The research was supported by the grant R01DA046468 from the National Institute on Drug Abuse of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the officials views of the NIH. It was conducted with the Accelerating Data Value Across a National Community Health Center Network (ADVANCE) Clinical Research Network, which is led by OCHIN in partnership with Health Choice Network, Fenway Health and OHSU, funded through contract R1-OCHIN-01-MC from the Patient-Centered Outcomes Research Institute.
Changes in Buprenorphine Prescribing in Community Health Centers
ARTICLE PUBLICATION DATE
26-Apr-2024
Blood test finds knee osteoarthritis up to eight years before it appears on x-rays
Early detection could lead to therapies that slow progression and restore joint health
DUKE UNIVERSITY MEDICAL CENTER
DURHAM, N.C. – A blood test successfully predicted knee osteoarthritis at least eight years before tell-tale signs of the disease appeared on x-rays, Duke Health researchers report.
In a study appearing April 26 in the journal Science Advances, the researchers validated the accuracy of the blood test that identifies key biomarkers of osteoarthritis. They showed that it predicted development of the disease, as well as its progression, which was demonstrated in their earlier work.
The research advances the utility of a blood test that would be superior to current diagnostic tools that often don’t identify the disease until it has caused structural damage to the joint.
“Currently, you’ve got to have an abnormal x-ray to show clear evidence of knee osteoarthritis, and by the time it shows up on x-ray, your disease has been progressing for some time,” said senior author Virginia Byers Kraus, M.D., Ph.D., a professor in the departments of Medicine, Pathology, and Orthopedic Surgeryat Duke University School of Medicine. “What our blood test demonstrates is that it’s possible to detect this disease much earlier than our current diagnostics permit.”
Osteoarthritis (OA) is the most common form of arthritis, afflicting an estimated 35 million adults in the U.S. and causing significant economic and societal impacts. While there are currently no cures, the success of potential new therapies could hinge on identifying the disease early and slowing its progression before it becomes debilitating.
Kraus and colleagues have focused on developing molecular biomarkers that can be used for both clinical diagnostic purposes and as a research tool to aid in the development of effective drugs. In previous studies, the blood biomarker test demonstrated 74% accuracy in predicting knee OA progression and 85% accuracy in diagnosing knee OA.
The current study further honed the test’s predictive capabilities. Using a large United Kingdom database, the researchers analyzed serum of 200 white women, half diagnosed with OA and the other half without the disease, matched by body mass index and age.
They found that a small number of biomarkers in the blood test successfully distinguished the women with knee OA from those without it, catching molecular signals of OA eight years before many of the women were diagnosed with the disease by x-ray.
“This is important because it provides more evidence that there are abnormalities in the joint that can be detected by blood biomarkers well before x-rays can detect OA,” Kraus said. “Early-stage osteoarthritis could provide a ‘window of opportunity’ in which to arrest the disease process and restore joint health.”
In addition to Kraus, study authors include Shuming Sun, Alexander Reed, Erik J. Soderblom, M Arthur Moseley, Kaile Zhou, Vaibhav Jain, Nigel Arden, and Yi-Ju Li.
The study received funding support from National Institutes of Health (R01-AR071450 and P30-AG028716).
JOURNAL
Science Advances
Location, location, location
How geography acts as a structural determinant of health
Riverside, Calif. -- In unincorporated communities in the United States-Mexico borderlands, historically and socially marginalized populations become invisible to the healthcare system, showing that geography acts as a structural determinant of health for low-income populations. So concludes a study by a University of California, Riverside, team that focused its attention on the borderland in Southern California, specifically, eastern Coachella Valley.
From September to December 2020, the team, led by Ann Cheney, an associate professor of social medicine, population, and public health in the School of Medicine, conducted interviews in collaboration with MarÃa Pozar, a community investigator and CEO of Conchita Servicios de la Comunidad, with 36 Latinx and Indigenous Mexican caregivers of children with asthma or respiratory distress. The researchers found communities in the “colonias” (unincorporated areas in the borderlands) lack basic critical infrastructure including healthcare access.
The U.S.-Mexico borderland is home to nearly 2.7 million Hispanic or Latinx individuals. The immigrant population in the colonias has limited English proficiency, health literacy levels, and income, and lower levels of formal education. Many are undocumented.
The study, published in the journal Social Science & Medicine, found the caregivers perceive U.S.-based physicians as not providing them with sufficient information since most physicians do not speak their language and do not adequately listen to or are dismissive of their concerns about their children’s respiratory health. The caregivers perceive Mexican-based physicians as providing them with a diagnosis and treatment plan, whereas U.S.-based physicians often prescribe medications and provide no concrete diagnosis.
“Further, only those with legal documentation status can cross the border, which contributes to disparities in children’s respiratory health,” Cheney said. “Thus, caregivers without legal status in the U.S. must access healthcare services in the U.S. for their children and receive, what these caregivers perceive, as suboptimal care.”
Cheney added she was surprised to learn that caregivers who did not have legal documentation status in the U.S. asked trusted family and friends to take their children across the border to receive healthcare services for childhood asthma and related conditions.
“Geography, meaning living in unincorporated communities, harms health,” she said. “Geography and the politics of place determines who can and cannot cross borders.”
Study participants discussed the distance they needed to travel to pediatric specialty care for the care and management of their children’s respiratory health problems. Some commented on the lack of interaction and communication with physicians during medical visits. Some participants commented on the lack of physicians’ knowledge about the connections between their children’s exposure to environmental hazards and poor respiratory health and allergic symptoms.
The research took place in four unincorporated rural communities — Mecca, Oasis, Thermal, and North Shore — in eastern Coachella Valley, along the northern section of the Salton Sea. People living in the colonias here are subject to the health effects of environmental hazards. Many are farmworkers living and working in the nearby agricultural fields. Most of the workforce lives in mobile parks and below the federal poverty line.
“In addition to toxic water and dust from the Salton Sea, other environmental health hazards, such as agriculture pesticide exposure, waste processing facilities, and unauthorized waste dumps, also contribute to this community’s high incidence of poor respiratory health,” said Gabriela Ortiz, the first author of the research paper and a graduate student in anthropology who works with Cheney. “These communities are vulnerable to the policies and governing decisions around exposure to environmental hazards and infrastructure development. The absence of infrastructure and lack of healthcare infrastructure limits their access to primary care and specialty care services.”
Ortiz explained that anthropologists and social scientists have long argued that environmental injustices are a product of structural violence.
“This is indirect violence caused by social structures and institutions that prevent individuals from meeting their basic needs because of political economic domination and class-based exploitation,” she said. “Understanding the complex interplay between geography, borderlands, and health is essential for coming up with effective public health policy and interventions.”
The title of the research paper is “Seeking care across the US-Mexico border: The experiences of Latinx and Indigenous Mexican caregivers of children with asthma or respiratory distress.”
Cheney, Ortiz, and Pozar were joined in the study by Ashley Moran and Sophia Rodriquez of UCR.
The study was funded by the National Institutes of Health/National Institute of Minority Health and Health Disparities.
The University of California, Riverside is a doctoral research university, a living laboratory for groundbreaking exploration of issues critical to Inland Southern California, the state and communities around the world. Reflecting California's diverse culture, UCR's enrollment is more than 26,000 students. The campus opened a medical school in 2013 and has reached the heart of the Coachella Valley by way of the UCR Palm Desert Center. The campus has an annual impact of more than $2.7 billion on the U.S. economy. To learn more, visit www.ucr.edu.
Seeking care across the US-Mexico border: The experiences of Latinx and Indigenous Mexican caregivers of children with asthma or respiratory distress
ARTICLE PUBLICATION DATE
24-Apr-2024
Getting dynamic information from static snapshots
In a new paper, UChicago researchers use machine learning insights to provide a better way for cancer and immunology researchers to study transcriptional dynamics of genes and cell-state transitions
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UNIVERSITY OF CHICAGO
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PART OF AN INTERDISCIPLINARY UNIVERSITY OF CHICAGO TEAM BEHIND A NEW METHOD OF USING STATIC DATA FROM SINGLE-CELL RNA SEQUENCING TO STUDY HOW CELLS AND GENES CHANGE OVER TIME. FROM LEFT, BIOPHYSICS GRADUATE STUDENT HANNA HIEROMNIMON, PRITZKER SCHOOL OF MOLECULAR ENGINEERING GRADUATE STUDENT JOEY FEDERICO, COMPUTER SCIENCE GRADUATE STUDENT RYAN ROBINETT, PME ASST. PROF. SAMANTHA RIESENFELD, CHEMISTRY GRADUATE STUDENT AND PAPER FIRST AUTHOR CHENG FRANK GAO, CHEMISTRY GRADUATE STUDENT JOSEPH SIFAKIS AND BIOPHYSICS GRADUATE STUDENT HOPE ANDERSON.
Imagine predicting the exact finishing order of the Kentucky Derby from a still photograph taken 10 seconds into the race.
That challenge pales in comparison to what researchers face when using single-cell RNA-sequencing (scRNA-seq) to study how embryos develop, cells differentiate, cancers form, and the immune system reacts.
In a paper published today in Proceedings of the National Academy of Sciences, researchers from the UChicago Pritzker School of Molecular Engineering and the Chemistry Department have created TopicVelo, a powerful new method of using the static snapshots from scRNA-seq to study how cells and genes change over time.
The team took an interdisciplinary, collaborative approach, incorporating concepts from classical machine learning, computational biology, and chemistry.
Researchers use scRNA-seq to get measurements that are powerful and detailed, but by nature are static.
“We developed TopicVelo to infer cell-state transitions from scRNA-seq data,” Riesenfeld said. “It's hard to do that from this kind of data because scRNA-seq is destructive. When you measure the cell this way, you destroy the cell.”
This leaves researchers a snapshot of the moment the cell was measured/destroyed. While scRNA-seq gives the best available transcriptome-wide snapshot, the information many researchers need, however, is how the cells transition over time. They need to know how a cell becomes cancerous or how a particular gene program behaves during an immune response.
To help figure out dynamic processes from a static snapshot, researchers traditionally use what’s called “pseudotime.” It’s impossible to watch an individual cell or gene’s expression change and grow in a still image, but that image also captured other cells and genes of the same type that might be a little further on in the same process. If the scientists connect the dots correctly, they can gain powerful insights into how the process looks over time.
Connecting those dots is difficult guesswork, based on the assumption that similar-looking cells are just at different points along the same path. Biology is much more complicated, with false starts, stops, bursts, and multiple chemical forces tugging on each gene.
Instead of traditional pseudotime approaches, which look at the expression similarity among the transcriptional profiles of cells, RNA velocity approaches look at the dynamics of transcription, splicing and degradation of the mRNA within those cells.
It’s a promising but early technology.
“The persistent gap between the promise and reality of RNA velocity has largely restricted its application,” the authors wrote in the paper.
To bridge this gap, TopicVelo puts aside deterministic models, embracing—and gleaning insights from—a far more difficult stochastic model that reflects biology’s inescapable randomness.
“Cells, when you think about them, are intrinsically random,” said Gao, the first author on the paper. “You can have twins or genetically identical cells that will grow up to be very different. TopicVelo introduces the use of a stochastic model. We're able to better capture the underlying biophysics in the transcription processes that are important for mRNA transcription.”
Machine learning shows the way
The team also realized that another assumption limits standard RNA velocity. “Most methods assume that all cells are basically expressing the same big gene program, but you can imagine that cells have to do different kinds of processes simultaneously, to varying degrees,” Riesenfeld said. Disentangling these processes is a challenge.
Probabilistic topic modeling—a machine learning tool traditionally used to identify themes from written documents—provided the UChicago team with a strategy. TopicVelo groups scRNA-seq data not by the types of cell or gene, but by the processes those cells and genes are involved in. The processes are inferred from the data, rather than imposed by external knowledge.
“If you look at a science magazine, it will be organized along topics like ‘physics,’ ‘chemistry’ and ‘astrophysics,’ these kinds of things,” Gao said. “We applied this organizing principle to single-cell RNA-sequencing data. So now, we can organize our data by topics, like ‘ribosomal synthesis,’ ‘differentiation,’ ‘immune response,’ and ‘cell cycle’. And we can fit stochastic transcriptional models specific to each process.”
After TopicVelo disentangles this kludge of processes and organizes them by topic, it applies topic weights back onto the cells, to account for what percentage of each cell’s transcriptional profile is involved in which activity.
According to Riesenfeld, “This approach helps us look at the dynamics of different processes and understand their importance in different cells. And that's especially useful when there are branch points, or when a cell is pulled in different directions.”
The results of combining the stochastic model with the topic model are striking. For example, TopicVelo was able to reconstruct trajectories that previously required special experimental techniques to recover. These improvements greatly broaden potential applications.
Gao compared the paper’s findings to the paper itself—the product of many areas of study and expertise.
“At PME, if you have a chemistry project, chances are there’s a physics or engineering student working on it,” he said. “It’s never just chemistry.”
Citation: “Dissection and Integration of Bursty Transcriptional Dynamics for Complex Systems,” Gao et al., Proceedings of the National Academy of Sciences, April 26, 2024. DOI: 10.1073/pnas.2306901121
Funding: This work was supported by the NIH NIGMS Award R35GM147400.
CREDIT: PHOTO BY BARBARA JOHNSTON/UNIVERSITY OF NOTRE DAME
Adding a pre-ketone supplement — a component of a high-fat, low-carb ketogenic diet — to a type of cancer therapy in a laboratory setting was highly effective for treating prostate cancer, researchers from the University of Notre Dame found.
Recently published online in the journal Cancer Research, the study from Xin Lu, the John M. and Mary Jo Boler Collegiate Associate Professor in the Department of Biological Sciences, and collaborators tackled a problem oncologists have battled: Prostate cancer is resistant to a type of immunotherapy called immune checkpoint blockade (ICB) therapy. ICB therapy blocks certain proteins from binding with other proteins and paves the way for our body’s fighter cells, T cells, to kill the cancer.
“Prostate cancer is the most common cancer for American men, and immunotherapy has been really influential in some other cancers, like melanoma or lung cancer, but it hasn’t been working almost at all for prostate cancer,” said Lu, who is affiliated with the Boler-Parseghian Center for Rare and Neglected Diseases. Adding a dietary supplement might overcome this resistance, the lead author in the study, Sean Murphy, suggested.
Murphy, a ’24 alumnus who was a doctoral student in Lu’s lab, had been following a keto diet himself. Knowing that cancer cells feed off of sugar, he decided that depriving mouse models of carbohydrates — a key component of the keto diet — might prevent cancer growth.
He divided the models into different groups: immunotherapy alone, ketogenic diet alone, a pre-ketone supplement alone, the ketogenic diet with the immunotherapy, the supplement with the immunotherapy, and the control. While the immunotherapy alone had almost no effect on the tumors (just like what happens to most patients with prostate cancer), both the ketogenic diet with the immunotherapy and the pre-ketone supplement with the immunotherapy reduced the cancer and extended the lives of the mouse models.
The supplement with the immunotherapy worked best.
“It turned out this combination worked really well,” Lu said. “It made the tumor become very sensitive to the immunotherapy, with 23 percent of the mice cured — they were tumor-free; in the rest, the tumors were shrinking really dramatically.”
The evidence points to the possibility that a supplement providing ketones, which are what is produced in the body when people eat a keto diet, might prevent the prostate cancer cells from being resistant to immunotherapy. This may lead to future clinical studies that examine how ketogenic diets or keto supplements could enhance cancer therapy.
While keto diets allow for minimal carbohydrates, the success of this study is not about the lack of carbohydrates, Murphy and Lu stressed. It is about the presence of the ketone body, a substance produced by the liver and used as an energy source when glucose is not available. The ketones disrupt the cycle of the cancer cells, allowing the T cells to do their job to destroy them.
The discovery was also exciting on a molecular level, Lu said. Any type of dietary study can suffer from the potential issue of causation: Are the results from the diet or other changes made because of the diet? But Lu and his collaborators confirmed their results using single-cell RNA sequencing, which examines the gene expression of single cells within the tumor.
“We found that this combination of the supplement and the immunotherapy reprogrammed the whole immune profile of the tumors and recruited many T cells into the tumors to kill prostate cancer cells,” Lu said.
The successful therapy also reduced the number of a type of immune cell called neutrophils. Once in the tumor microenvironment, neutrophils’ natural properties become greatly distorted, and they become largely responsible for inhibiting T cell activities and allowing more tumor progression. Dysregulation of neutrophils is also associated with many other diseases.
“With the main ketone body depleting neutrophils, it opens the door for investigating the effects of the keto diet and the ketone supplement on diseases ranging from inflammatory bowel disease to arthritis,” Murphy said.
Lu agreed.
“What’s exciting is that we’re getting closer to the mechanism, backed up by genetic models and what we’re seeing in the tumors themselves, of why this works,” he said.
Co-authors include Sharif Rahmy, Dailin Gan, Guoqiang Liu, Yini Zhu, Maxim Manyak, Loan Duong, Jianping He, James H. Schofield, Zachary T. Schafer, Jun Li and Xuemin Lu, all from the University of Notre Dame.
The research was supported by a grant from the American Institute for Cancer Research, funding from the National Institutes of Health and a core facility grant from Indiana Clinical and Translational Sciences Institute. Other support included the Department of Defense and the Boler Family Foundation at the University of Notre Dame. A provisional patent application has been filed based on this study by the IDEA Center at Notre Dame.
