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Tag: University of Chicago Medical Center

  • Nutrient found in beef and dairy improves immune response to cancer

    Nutrient found in beef and dairy improves immune response to cancer

    Newswise — Trans-vaccenic acid (TVA), a long-chain fatty acid found in meat and dairy products from grazing animals such as cows and sheep, improves the ability of CD8+ T cells to infiltrate tumors and kill cancer cells, according to a new study by researchers from the University of Chicago.

    The research, published this week in Nature, also shows that patients with higher levels of TVA circulating in the blood responded better to immunotherapy, suggesting that it could have potential as a nutritional supplement to complement clinical treatments for cancer.

    “There are many studies trying to decipher the link between diet and human health, and it’s very difficult to understand the underlying mechanisms because of the wide variety of foods people eat. But if we focus on just the nutrients and metabolites derived from food, we begin to see how they influence physiology and pathology,” said Jing Chen, PhD, the Janet Davison Rowley Distinguished Service Professor of Medicine at UChicago and one of the senior authors of the new study. “By focusing on nutrients that can activate T cell responses, we found one that actually enhances anti-tumor immunity by activating an important immune pathway.”

    Finding nutrients that activate immune cells

    Chen’s lab focuses on understanding how metabolites, nutrients and other molecules circulating in the blood influence the development of cancer and response to cancer treatments. For the new study, two postdoctoral fellows, Hao Fan, PhD and Siyuan Xia, PhD, both co-first authors, started with a database of around 700 known metabolites that come from food and assembled a “blood nutrient” compound library consisting of 235 bioactive molecules derived from nutrients. They screened the compounds in this new library for their ability to influence anti-tumor immunity by activating CD8+ T cells, a group of immune cells critical for killing cancerous or virally infected cells.

    After the scientists evaluated the top six candidates in both human and mouse cells, they saw that TVA performed the best. TVA is the most abundant trans fatty acid present in human milk, but the body cannot produce it on its own. Only about 20% of TVA is broken down into other byproducts, leaving 80% circulating in the blood. “That means there must be something else it does, so we started working on it more,” Chen said.

    The researchers then conducted a series of experiments with cells and mouse models of diverse tumor types. Feeding mice a diet enriched with TVA significantly reduced the tumor growth potential of melanoma and colon cancer cells compared to mice fed a control diet. The TVA diet also enhanced the ability of CD8+ T cells to infiltrate tumors.

    The team also performed a series of molecular and genetic analyses to understand how TVA was affecting the T cells. These included a new technique for monitoring transcription of single-stranded DNA called kethoxal-assisted single-stranded DNA sequencing, or KAS-seq, developed by Chuan He, PhD, the John T. Wilson Distinguished Service Professor of Chemistry at UChicago and another senior author of the study. These additional assays, done by both the Chen and He labs, showed that TVA inactivates a receptor on the cell surface called GPR43 which is usually activated by short-chain fatty acids often produced by gut microbiota. TVA overpowers these short-chain fatty acids and activates a cellular signaling process known as the CREB pathway, which is involved in a variety of functions including cellular growth, survival, and differentiation. The team also showed that mouse models where the GPR43 receptor was exclusively removed from CD8+ T cells also lacked their improved tumor fighting ability.

    Finally, the team also worked with Justin Kline, MD, Professor of Medicine at UChicago, to analyze blood samples taken from patients undergoing CAR-T cell immunotherapy treatment for lymphoma. They saw that patients with higher levels of TVA tended to respond to treatment better than those with lower levels. They also tested cell lines from leukemia by working with Wendy Stock, MD, the Anjuli Seth Nayak Professor of Medicine, and saw that TVA enhanced the ability of an immunotherapy drug to kill leukemia cells.

    Focus on the nutrients, not the food

    The study suggests that TVA could be used as a dietary supplement to help various T cell-based cancer treatments, although Chen points out that it is important to determine the optimized amount of the nutrient itself, not the food source. There is a growing body of evidence about the detrimental health effects of consuming too much red meat and dairy, so this study shouldn’t be taken as an excuse to eat more cheeseburgers and pizza; rather, it indicates that nutrient supplements such as TVA could be used to promote T cell activity. Chen thinks there may be other nutrients that can do the same.

    “There is early data showing that other fatty acids from plants signal through a similar receptor, so we believe there is a high possibility that nutrients from plants can do the same thing by activating the CREB pathway as well,” he said.

    The new research also highlights the promise of this “metabolomic” approach to understanding how the building blocks of diet affect our health. Chen said his team hopes to build a comprehensive library of nutrients circulating in the blood to understand their impact on immunity and other biological processes like aging.

    “After millions of years of evolution, there are only a couple hundred metabolites derived from food that end up circulating in the blood, so that means they could have some importance in our biology,” Chen said. “To see that a single nutrient like TVA has a very targeted mechanism on a targeted immune cell type, with a very profound physiological response at the whole organism level—I find that really amazing and intriguing.”

    The study, “Trans-vaccenic acid reprograms CD8+ T cells and anti-tumor immunity,” was supported by the National Institutes of Health (grants CA140515, CA174786, CA276568, 1375 HG006827, K99ES034084), a UChicago Biological Sciences Division Pilot Project Award, the Ludwig Center at UChicago, the Sigal Fellowship in Immuno-oncology, the Margaret E. Early Medical Research Trust, the AASLD Foundation a Harborview Foundation Gift Fund, and the Howard Hughes Medical Institute.

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  • Albert Bendelac, pathologist and former chair of the University of Chicago Committee on Immunology, 1956-2023

    Albert Bendelac, pathologist and former chair of the University of Chicago Committee on Immunology, 1956-2023

    Newswise — Albert Bendelac, MD, PhD, the A.N. Pritzker Distinguished Service Professor of Pathology at the University of Chicago, died at his home on August 23, 2023, surrounded by family. He had just celebrated his 67th birthday.

    Known for his passion for immunology, his mentorship of students and young faculty, and his broad scientific thinking, Bendelac joined the faculty in 2002 as an established investigator. His research had already demonstrated that CD4 and CD8 T cells were required for the development of type-1 diabetes and had described a novel subset of T cells that expressed Natural Killer cell antigens (NKT cells), discovering CD1d as their restricting element.

    “There is little doubt that he remained the leader in the field of NKT cell biology,” said Vinay Kumar, MBBS, MD, the Lowell T Coggeshall Distinguished Professor of Pathology and Chair Emeritus.

    Bendelac’s seminal discovery came in 1995 when he first described NKT cells in the journal Science, and later in 2005, finding that lysosomal glycosphingolipid ceramide is the natural ligand for NKT cells.  More largely, he explored the fundamental question of thymic selection of innate lymphocytes, and in 2008 identified the transcription factor PLZF as the master regulator of NKT, MAIT, and ILC development. In his final years of research, he expanded his work to mucosal IgA B cells. He published more than 100 papers, several of which are cited more than 1,000 times.

    Colleagues from across the country remembered Bendelac’s rigorous approach and contributions to the field.

    Marco Colonna, the Robert Rock Belliveau Professor of Pathology and Immunology at Washington University, said, “I always admired Albert for his genius, unwavering experimental rigor, and fearless approach to exploring new frontiers in immunology. His upfront and uncompromising nature made him a true and authentic person.”

    Jason Cyster, Professor of Microbiology and Immunology and Howard Hughes Investigator at the University of California San Francisco, said, “I was always inspired by the quality of his work. His insights into innate lymphocytes were truly ahead of their time.” And Marc Jenkins, the Regents Professor and Director of the Center for Immunology at the University of Minnesota, said simply, “Albert made his mark on the world.”

    In addition to his groundbreaking research on lymphocyte biology, Bendelac made immeasurable contributions toward establishing UChicago’s Committee on Immunology (COI) as a home of leading-edge, multi-disciplinary research and a premiere training program for young scientists.

    Colleagues cite his Advanced Immunology course, which was widely regarded by many trainees as the most demanding and rewarding course of their graduate tenure, and which set the standard for other COI instructors. His Immunobiology course for undergraduate students, the first step in the Concentration on Immunology, was very popular and uniformly highly rated.

    Daria Esterhazy, PhD, Assistant Professor of Pathology, was recruited by Bendelac to UChicago in 2018 as part of his successful efforts to recruit junior faculty in immunology. “As of 2019, he shared an entire floor of a building unit with me and the other assistant professor recruits, Dr. Andrew Koh and Dr. David Zemmour. It was Dr. Bendelac’s initiative to install such an immunology floor and move himself from another space for the sake of fostering a new generation of independent investigators,” she said.

    “He was incredibly invested in and supportive of the next generation of immunologists, from undergraduate teaching, to conceiving of the graduate teaching curriculum in immunology, to recruiting multiple junior faculty members and helping them thrive.”

    The former chair of the COI, Bendelac received multiple awards throughout his career, including the Quantrell Teaching Award for Excellence in undergraduate teaching in 2019. At the time of the award, he explained that immunology is an incredibly complex field, and the amount of information students have to process can be daunting. Bendelac said the key to keeping undergraduates engaged as he introduces them to the field is to convey this complexity without overwhelming them with details.

    “You don’t want to turn them off. You want to excite them and inspire them,” he said. “My mission is to cover all the key aspects of the field but not go into excruciating detail, like knowing the music but not necessarily all the words.”

    It was an award that his wife, Bana Jabri, MD, PhD, the Sarah and Harold Lincoln Thompson Distinguished Service Professor of Medicine and current Chair of the Committee on Immunology, also won in 2017. Colleagues described the two as a formidable team, working in different areas of immunology and together helping establish UChicago as a center of excellence in immunology.

    “Albert had a vision of scientific excellence that was deeply infectious – he challenged and inspired others to dig deeper both conceptually and technically,” said Peter Savage, PhD, Associate Professor of Pathology. “He had high expectations of his colleagues and trainees and led by example. I never saw him flinch or hesitate to tackle a problem, or to put in the hard work necessary to do so.  Ultimately, this made an indelible impression that was inspiring to many of us.”

    Bendelac earned his MD from University Paris VI in 1985, and his PhD in immunology from University Paris VII in 1992. From 1994-2002, he was an associate and then assistant (tenured) professor of molecular biology at Princeton University, and before that was a visiting fellow and then visiting scientist at the National Institutes of Health.

    Outside the lab, he enjoyed morning runs with his border collies along Lake Michigan, movies (particularly European cinema), literature, good food and wine, and he was an excellent cook.

    In addition to his wife, he is survived by their children, Aude, Raphaëlle, and Julien.

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  • New study shows promising evidence for sickle cell gene therapy

    New study shows promising evidence for sickle cell gene therapy

    New research published in the New England Journal of Medicine indicates that stem cell gene therapy may offer a promising, curative treatment for the painful, inherited blood disorder sickle cell disease (SCD).

    The findings from a new clinical trial, published August 31, add to the body of evidence supporting gene therapy as a treatment for sickle cell disease, which primarily impacts people of color.

    About 100,000 Americans have sickle cell disease, according to the U.S. Centers for Disease Control and Prevention. The condition, which can cause a lifetime of pain, health complications and expenses, affects one in 365 Black babies born in the U.S. and one in 16,300 Hispanic babies.

    Until recently, the only treatment options have been intensive bone marrow transplants from siblings or matched donors. But other curative therapies are now on the horizon. The University of Chicago Medicine Comer Children’s Hospital was one of three sites to enroll patients in the clinical trial, which tested a stem cell gene therapy to treat sickle cell disease.

    As part of the trial, researchers used CRISPR-Cas9 to edit specific genes in stem cells — the building blocks of blood cells — taken from each patient. The edits increased the cells’ production of fetal hemoglobin (HbF), a protein that can replace unhealthy, sickled hemoglobin in the blood and protect against the complications of sickle cell disease. The patients then received their own edited cells as therapeutic infusions.

    The therapy was the second for this disease to use CRISPR-Cas9 technology and the first to target a new genetic area and use cryopreserved stem cells with the hope of increasing access to such a treatment. Other gene therapy studies for SCD have used lentiviruses — a type of virus often modified and used for gene editing which remain in the cell long-term. No foreign material remains in stem cells edited with CRISPR-Cas9.

    Trial participants who received the CRISPR-edited stem cells reported a decrease in vaso-occlusive events, a painful phenomenon that occurs when sickled red blood cells accumulate and cause a blockage.

    “The biggest take-home message is that there are now more potentially curative therapies for sickle cell disease than ever before that lie outside of using someone else’s stem cells, which can bring a host of other complications,” said James LaBelle, MD, PhD, director of the Pediatric Stem Cell and Cellular Therapy Program at UChicago Medicine and Comer Children’s Hospital and senior author of the study. “Especially in the last 10 years, we’ve learned about what to do and what not to do when treating these patients. There’s been a great deal of effort towards offering patients different types of transplants with decreased toxicities, and now gene therapy rounds out the set of available treatments, so every patient with sickle cell disease can get some sort of curative therapy if needed. At UChicago Medicine, we’ve built infrastructure to support new approaches to sickle cell disease treatment and to bring additional gene therapies for other diseases.”

    As the scientific community continues to refine and expand the applications of gene therapy, the potential for curative treatments for diseases like sickle cell disease is becoming more of a transformative reality. The journey is ongoing, with the need for long-term follow-up and further research, but this study provides an encouraging glimpse into a future of effective genetic interventions.

    In the larger context of therapeutic development, LaBelle stressed the importance of the study’s contribution to the growing body of evidence supporting the viability of gene therapy as a treatment for sickle cell disease. Two other gene therapies for the disease are awaiting FDA approval this year.

    “The data from this trial supports bringing on similar gene therapies for sickle cell disease and for other bone marrow-derived diseases. If we didn’t have this data, those wouldn’t move forward,” he said.

    The study, “CRISPR-Cas9 Editing of the HBG1/HBG2 Promoters to Treat Sickle Cell Disease,” was published in NEJM in August 2023. Co-authors include Radhika Peddinti, along with researchers from St. Jude Children’s Research Hospital, Memorial Sloan Kettering Cancer Center, Novartis Institutes for BioMedical Research, Children’s Hospital Los Angeles, and IRCCS San Raffaele Hospital in Milan, Italy. The authors also acknowledged research coordinator Christopher Omahen and Amittha Wickrema, director of UChicago’s cell processing facility.

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  • Andrew Chang joins UChicago Medicine as Chief Marketing Officer

    Andrew Chang joins UChicago Medicine as Chief Marketing Officer

    Newswise — Andrew “Andy” Chang has been selected as UChicago Medicine’s new Vice President, Chief Marketing Officer. He joins the health system August 28.

    Chang’s robust marketing career has spanned numerous industries during the past two decades. He comes to UChicago Medicine from VillageMD, which provides primary, multispecialty and urgent care services across the U.S. As vice president of marketing at VillageMD, Chang spent the past three years overseeing the company’s marketing strategy, brand, physician outreach, analytics and marketing technology platforms. Before joining VillageMD, Chang served as executive director of marketing and physician outreach at Piedmont Healthcare, a 22-hospital system based in Atlanta. Prior to his work in healthcare, he led marketing efforts at the real estate firm Stan Johnson Company, various divisions of shipping company UPS and AirTran Airways.

    At UChicago Medicine, Chang will lead the health system’s Marketing Department and will develop and maintain strategic, cohesive, and successful brand and digital marketing strategies. He brings an innovative, analytical and data-focused approach to marketing and will move UChicago Medicine to the forefront of healthcare marketing. He will align marketing messaging for UChicago Medicine’s evolving clinical enterprise. He also will work to grow the business by promoting the system’s world-class network, medical care and research enterprise.

    Chang has a master’s degree in business administration from Wake Forest University and a bachelor’s degree in molecular and cell biology from the University of California, Berkeley.

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  • Krista Curell named UChicago Health System COO

    Krista Curell named UChicago Health System COO

    Newswise — Krista Curell has been appointed Executive Vice President and Chief Operating Officer for the University of Chicago Health System, where she will work to ensure a coordinated and comprehensive approach that supports the organization’s future growth.

    Working collaboratively with the leaders at the various sites, Curell will guide day-to-day operations across the UChicago Medicine health system and focus on optimizing and fully integrating operations at the care sites, including Ingalls Memorial Hospital.

    A nurse and an attorney, Curell has dedicated her professional career to the University of Chicago Medical Center since 2001.

    Her new role builds on her work as Chief Transformation and Integration Officer, a position she has had since March 2021, and her more recent additional responsibilities as Chief Administration Officer. In these capacities she has created integrated structures for the departments of Risk Management, Patient Safety & Quality Performance Improvement, Patient Experience, Compliance, Human Resources and other shared services.

    Curell’s credentials also include her experience and demonstrated strategic leadership over the enterprise’s Emergency Operations Division, serving as Incident Commander of the Hospital Incident Command Structure over the past decade.

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  • Barry Arnason, first Chair of Neurology at UChicago, 1933-2023

    Barry Arnason, first Chair of Neurology at UChicago, 1933-2023

    Newswise — Barry Arnason, MD, the founding Chair of the Department of Neurology at the University of Chicago, died on July 17, 2023. He was 89 years old.

    Arnason joined the faculty at UChicago in 1976 and led the department until 1996, establishing it as a nationally prominent program for both research and patient care. As a physician-scientist, he is considered to be one of the founders of the field of neuro-immunology, which focuses on understanding how the immune system and the nervous system communicate with each other and maintain the body’s overall health.

    Arnason was an author on more than 400 scientific papers on the underlying causes of autoimmunity, neurological diseases, and the development of therapeutic interventions. He was an investigator on more than 70 clinical trials, including studies that led to the approval of interferon-β1b (Betaseron) as the first therapy for relapsing multiple sclerosis (MS). He played a pivotal role in discovering how dysfunctional T cells affect the development of multiple sclerosis, which led him to breakthrough studies that influenced drug management therapies, ultimately affecting how people with MS manage the disease. He also studied what happens—or does not happen—during MS attacks to further advance therapies that may not involve T cells at all. He earned numerous prizes over his long career, including the prestigious John Dystel Prize in MS Research from the American Academic of Neurology and the National MS Society (2014) and election to the American Society of Clinical Investigation in 1974.

    Former colleagues and trainees remember Arnason as a polymath who spoke multiple languages, lectured on six different continents, and knew incredible amounts of history and culture in addition to his professional work. He was gifted at making connections and offering insights for colleagues, even outside his field of expertise, and made an indelible impact on their work.

    “He read over everyone’s grant proposals and added incredibly insightful comments, no matter what the topic,” said Anthony Reder, MD, Professor of Neurology, who joined the department under Arnason in 1982. “I would be working on a proposal about MS and no one else I talked to could add content; but then I’d talk to Barry and he would double what I had done. He was so good at connecting ideas.”

    Arnason was a mentor for scores of clinicians, scientists, residents, and fellows, so numerous that a former trainee of his has presided at the Department of Neurology’s annual Arnason Resident Research Symposium for the past 20 years. Jack Antel, MD, Professor of Neurology and Neurosurgery at McGill University in Montreal, was part of the first cohort of faculty Arnason recruited to UChicago, working with him for 10 years. He called Arnason a true original thinker, equally capable at patient care, clinical research, and basic investigations in animal model systems, who also fostered a collaborative atmosphere in the department.

    “If you had something to say, his door was always open,” Antel said. “He treated the faculty like one big family. We were a very cohesive group, like a series of atoms working together as a molecule. He pushed everyone, but he shared his ideas and wanted everyone to do well.”

    Born and raised in Canada, Arnason graduated from University of Manitoba Medical School before going to Massachusetts General Hospital in 1958 to complete his neurologic training and a fellowship in the laboratory of Byron Waksman. He served on the faculty at Harvard Medical School until he was recruited to UChicago. Following his tenure as Department Chair, he remained on the faculty until he retired in 2020, and actively continued MS immunology research until his death.

    Arnason was predeceased by his beloved wife Joan, who was a pillar of the university and Hyde Park community and actively helped young people. They are survived by their children Stephen, Jon, and Eva.

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  • People with alcohol use disorder impaired after heavy drinking, despite claims of higher tolerance

    People with alcohol use disorder impaired after heavy drinking, despite claims of higher tolerance

    Newswise — While heavy drinkers can tolerate a certain amount of alcohol better than light or moderate drinkers, the concept of “holding your liquor” is more nuanced than commonly believed, according to new research from the University of Chicago.

    The researchers conducted the study with three groups of young adults in their 20s with different drinking patterns. They found that drinkers with alcohol use disorder (or AUD, traditionally known as alcoholism) displayed less impairment on fine motor and cognitive tasks than light or heavy social drinkers after consuming a standard intoxicating dose—equivalent to four to five drinks that produce breathalyzer readings of 0.08-0.09%, i.e., the threshold for drunk driving. Yet when those drinkers with AUD consumed a higher amount akin to their usual drinking habits—equivalent to seven to eight drinks and breathalyzer readings of 0.13%–they showed significant impairment on those same tasks, more than double their impairment at the standard intoxicating dose that did not return to baseline performance three hours after drinking.

    “There’s a lot of thinking that when experienced drinkers (those with AUD) consume alcohol, they are tolerant to its impairing effects,” said Andrea King, PhD, Professor of Psychiatry and Behavioral Neuroscience at UChicago and senior author of the study. “We supported that a bit, but with a lot of nuances. When they drank alcohol in our study at a dose similar to their usual drinking pattern, we saw significant impairments on both the fine motor and cognitive tests that was even more impairment than a light drinker gets at the intoxicating dose.”

    A study of different drinking patterns

    The new paper, published this week in Alcohol: Clinical and Experimental Research, is part of the Chicago Social Drinking Project, an ongoing research study started by King in 2004 that examines the effects of common substances like alcohol, caffeine, and antihistamines on mood, performance, and behavior in people with a wide range of alcohol drinking patterns. For the latest research, they worked with three groups of participants based on their binge drinking patterns, i.e., consuming five or more drinks for a man or four or more for a woman. The groups were light drinkers who do not binge drink, heavy social drinkers who binge drink several times a month, and drinkers who meet the criteria for AUD and binge drink frequently, at least one third or more days in a typical month.

    In a clinical setting, the research team told participants they would be receiving a drink containing either alcohol, a stimulant, a sedative, or a placebo. The alcoholic beverage was a flavored drink mix in water with 190-proof alcohol at 16% volume based on body weight, which was equivalent to four to five drinks, a high dose considered enough to intoxicate a typical drinker (female participants received a dose that was 85% of that for males to adjust for sex differences in metabolism). The participants consumed the drink over a 15-minute period.

    At 30, 60, 120, and 180 minutes after drinking the beverage, the participants took a breathalyzer test and completed two performance tasks. The first was a fine motor task that asked them to retrieve, rotate, and insert a grooved metal peg into 25 randomly slotted holes on a 4×4” metal board; participants were scored on how long it took to fill all 25 holes. The second test was paper and pencil task to test cognitive skill, in which the participants had 90 seconds to input symbols from a key pair onto a numbered grid and were scored on how many correct symbols they provided.

    At the 30- and 180-minute intervals, participants were also asked to report how impaired they felt, from “not at all” to “extremely.” The AUD and heavy social drinkers both reported feeling less impaired than the light drinkers. While they did show less overall alcohol impairment on the motor and cognitive tests, at the 30-minute interval they had similar slowing on the fine motor test as the light drinkers. They also recovered quicker to their baseline levels, supporting the notion that they had more tolerance and can “hold their liquor” better than people who don’t drink as much.

    However, people with AUD do not often stop drinking at four or five drinks and engage in high intensity drinking.  Thus, a subset of the drinkers with AUD in the study participated in a separate session where they drank a beverage more consistent with their regular drinking habits, equivalent to about seven or eight drinks. At this higher dose of alcohol, they showed more than double the amount of mental and motor impairment than after they had the standard intoxicating dose. They also never got back to their baseline level of performance, even after three hours. Their level of impairment even exceeded that of the light drinkers who consumed the standard dose, suggesting that the physical effects of the alcohol add up the more someone drinks, experienced or not.

    “I was surprised at how much impairment that group had to that larger dose, because while it’s 50% more than the first dose, we’re seeing more than double the impairment,” King said. 

    The double-edged sword of intoxication

    King’s group has conducted other research showing that heavy social drinkers and those with AUD are more sensitive to the pleasurable effects of alcohol, and want to drink more alcohol than their lighter drinking counterparts, compounding the issue. “They’re having the desire or craving to drink more and more, even though it’s impairing them. It’s really a double-edged sword,” she said.

    Annual deaths caused by drunk driving have fallen significantly after the national minimum drinking age was set at 21 in 1984 and the public awareness campaigns that followed. Despite these successes, the Centers for Disease Control and Prevention reports that more than 140,000 people die from excessive alcohol use in the U.S. each year, and 30% of traffic fatalities still involve alcohol intoxication. King says that a more nuanced understanding of the effects of intoxication could begin to prevent more harm.

    “It’s costly to our society for so many reasons, that’s why this study is just so important to understand more,” she said. “I’m hoping we can educate people who are experienced high-intensity drinkers who think that they’re holding their liquor or that they’re tolerant and won’t experience accidents or injury from drinking.  Their experience with alcohol only goes so far, and excessive drinkers account for most of the burden of alcohol-related accidents and injury in society. This is preventable with education and treatment.”

    The study, “Holding your liquor: Comparison of alcohol-induced psychomotor impairment in drinkers with and without alcohol use disorder,” was supported by the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse. Additional authors include Nathan Didier, Ashley Vena, Abigayle Feather, and Jon Grant from the University of Chicago.

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  • UChicago Medicine, AdventHealth launch new joint venture to expand health services in western suburbs

    UChicago Medicine, AdventHealth launch new joint venture to expand health services in western suburbs

    Newswise — The University of Chicago Medicine and AdventHealth have closed on a transaction to form a joint venture called UChicago Medicine AdventHealth, which will combine the expertise and resources of both organizations to bring academic medicine to the western suburbs.

    The two organizations announced a definitive agreement to affiliate in September 2022, with plans for UChicago Medicine to acquire a controlling interest in AdventHealth’s Great Lakes Region, which includes its four Illinois hospitals in Bolingbrook, Glendale Heights, Hinsdale and La Grange along with a network of nearly 50 physicians’ offices and outpatient locations.

    The AdventHealth Great Lakes Region’s facilities will be co-branded as UChicago Medicine AdventHealth to build upon the complementary strengths of the two organizations, with UChicago Medicine’s national reputation as an academic health system and AdventHealth’s focus on delivering outstanding medical care in community settings.

    “With the launch of this affiliation, we are blessed to continue to build on the rich legacy of whole-person care and further our mission and commitment to making these communities healthier for years to come,” said Terry Shaw, president/CEO of AdventHealth.

    Under the new joint venture, which became official January 1, 2023, UChicago Medicine gains a controlling interest in AdventHealth’s Great Lakes Region. AdventHealth retains the remaining ownership and will continue to manage daily operations of all facilities. Both UChicago Medicine and AdventHealth will maintain their separate system-level governance and administrative structures.

    Physicians of UChicago Medicine and AdventHealth Great Lakes will partner and coordinate care across both organizations to deliver high-quality, value-based care. This collaboration also will lead to an excellent patient experience and improved outcomes for patients.

    “The biggest benefit of this partnership is to patients,” said Tom Jackiewicz, president of the University of Chicago Medical Center, the hub of the UChicago Medicine health system. “AdventHealth Great Lakes’ patients now will have seamless access to UChicago Medicine’s specialty and subspecialty care and the latest clinical trials without the commute.”

    “In the same vein, UChicago Medicine patients who live in the western suburbs will now have access to AdventHealth’s exceptional quality, community-based care,” said Thor Thordarson, president and CEO of AdventHealth’s Great Lakes Region. “Working together, we can accomplish more for our patients and communities, and our shared resources and expertise will mean a healthier future for the greater Chicagoland area.”

    Medical teams from both organizations will be working in the coming months to expand programs and services, recruit more physicians and deliver even better care. To lead that effort, Sandra Valaitis, MD, has been appointed UChicago Medicine’s Chief Physician for the affiliation. Valaitis currently serves as UChicago Medicine’s Section Chief of Gynecology and Reconstructive Pelvic Surgery and Vice Chair of Faculty Affairs.

    In her new position, she will be responsible for physician collaboration, clinical integration and program development for the new joint venture. She will be working closely with Bela Nand, MD, Chief Medical Officer at UChicago Medicine AdventHealth Hinsdale and La Grange, who will lead the clinical integration efforts for the AdventHealth Great Lakes Region facilities.

    “I am excited to work together with my colleagues at UChicago Medicine and AdventHealth to ensure we’re building bridges between organizations that will enable us to better connect care for patients — whether they’re seeing their long-time family doctor in the western suburbs or a sub-specialist in Hyde Park,” said Valaitis.

    The affiliation is the latest move for UChicago Medicine, an integrated academic health system that includes hospitals, outpatient clinics and physician practices throughout Chicagoland as well as in the suburbs and Northwest Indiana. UChicago Medicine has been working for many years on developing and strengthening a healthcare ecosystem for communities on the South Side and beyond. That includes plans to build Chicago’s first freestanding comprehensive cancer facility on its medical campus on the South Side, where cancer is the second-leading cause of death. It’s also building a 130,000-square-foot multispecialty ambulatory center in Crown Point to serve the growing population in Northwest Indiana. It is also collaborating with 12 community providers on the South Side Healthy Community Organization collaborative, which is working to improve access to quality care for more than 400,000 people who live on Chicago’s South Side.

    AdventHealth is a faith-based health system headquartered in Florida with more than 50 hospital campuses in nine states and more than 80,000 team members, 2,400 employed physicians and almost 18,000 medical staff providers across the organization. AdventHealth’s Great Lakes Region includes UChicago Medicine AdventHealth Bolingbrook, UChicago Medicine AdventHealth GlenOaks, UChicago Medicine AdventHealth La Grange and UChicago Medicine AdventHealth Hinsdale, which has been serving the community for more than 100 years, as well as nearly 50 primary and specialty practice locations and two multispecialty ambulatory centers. The Carol Stream and Woodridge ambulatory centers offer primary and specialty care providers, diagnostic imaging and lab services.

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  • Increased mitochondria and lipid turnover reduces risk for liver cancer

    Increased mitochondria and lipid turnover reduces risk for liver cancer

    Newswise — Alcohol consumption and hepatitis C viral infection are known risk factors for causing hepatocellular carcinoma, the most common form of liver cancer. Apart from these, obesity-associated nonalcoholic fatty liver disease has emerged as a major contributing factor for hepatocellular carcinoma in Western societies. The mechanisms underlying obesity-induced liver cancer are not well understood.

    A new study published this week in the journal Science Advances by University of Chicago researchers showed that in a mouse model, deletion of the BNIP3 protein resulted in decreased turnover of mitochondria and lipid droplets that led to the development of fatty liver and, ultimately, liver cancer. In human liver cancer, they also showed that loss of BNIP3 expression was linked to increased lipids and worse prognosis.

    “My lab is interested in mitochondria and the turnover of mitochondria in normal physiological settings, but also in cancer. In our studies, we work on a protein called BNIP3 that functions as a mitochondrial cargo receptor,” said Kay Macleod, PhD, senior author of the paper and a professor in the Ben May Department for Cancer Research at the University of Chicago Medicine Comprehensive Cancer Center. “Normally, this protein is significantly upregulated in the liver in response to fasting in mice, where it plays a role in protecting the liver from fat accumulation; however, eliminating this protein caused fatty liver. So we studied this further to understand the underlying mechanisms of how loss of BNIP3 leads to lipid accumulation in the normal liver as well as liver cancer.”

    To understand BNIP3 involvement in the prevention of lipid accumulation and fatty liver condition, liver cancer was induced using chemical carcinogens in two sets of mice, one with BNIP3 intact and the other with BNIP3-deleted. The research team observed that tumors developed earlier and grew faster in BNIP3-deleted mice. Moreover, these tumors were full of fat, whereas tumors in BNIP3-intact mice were smaller and didn’t have lipids in them. When these tumors were followed over time, BNIP3-intact mice also developed lipid accumulation similar to that of BNIP3-deleted mice. More interestingly, BNIP3 had been silenced, suggesting that there is a selection for loss of BNIP3 in liver cancer as the disease progresses.

    These findings were consistent with human liver cancer patient data that reported a better prognosis in patients who had BNIP3 and less lipids in their tumors compared to patients who had a very high expression of genes involved in lipid synthesis. The data again suggests that BNIP3 is acting to suppress tumorigenesis in hepatocellular carcinoma by preventing lipid accumulation. Then the next question is how does BNIP3 regulate lipids?

    When BNIP3 was reintroduced using lentivirus into hepatocellular carcinoma cells that lacked BNIP3, tumor cells stopped accumulating lipids, and they didn’t multiply or grow as fast as the ones that lacked BNIP3. The researchers showed that this was happening due to BNIP3 causing turnover of lipids with mitochondria in a degradative cellular process that they call “mitolipophagy.”

    Fatty liver is a growing health issue in Western societies because of diet. “Eating too much food and eating the wrong kind of food causes extra fat to be stored in the liver. When liver cells (hepatocytes) get overburdened with lipids, they undergo death, which leads to regenerative growth of liver cells. If this process is uninterrupted, it leads to hepatocellular carcinoma,” Macleod said.

    Next, her team wondered how reduced lipid droplet turnover prevents hepatocellular carcinoma. Lipid droplets store a variety of lipids that are used to make cell membranes. If a cell is growing or multiplying, it requires a lot more membrane. BNIP3 will limit the number of phospholipids in the cell thereby limiting the lipids required for new cell generation.

    “BNIP3 is both preventing initiation of tumors and also limiting progression of tumors that are already formed by preventing them from growing faster or becoming more aggressive,” Macleod said.

    This work suggests that for a hepatocellular carcinoma to actually to form, it has to get rid of BNIP3. This implies that if there was a way to somehow prevent BNIP3 from being silenced, this could limit liver tumor growth or prevent fatty liver in the first place.

    “I think the most exciting thing is that BNIP3 does more than just promote the turnover of mitochondria. By promoting the interaction and functionality of the mitochondria, it is actually regulating other organelles in the cell,” Macleod said.

    Much attention has been paid to tumor metabolism and how to target this process in cancers. Most of that tends to focus on amino acids and glucose metabolism but not as much on lipid biology. Understanding more about how lipid metabolism is deregulated in cancer has not been as heavily researched. The researchers’ future work focuses on understanding how BNIP3 is regulated in disease conditions as well as with age. Meanwhile, they are also interested in a number of other genes that play important roles in response to nutrient stress.

    The study, “Lipid droplet turnover at the lysosome inhibits growth of hepatocellular carcinoma in a BNIP3- 3 dependent manner” was supported by NIH R01 849 CA200310 and NIH T32 CA009594. Additional authors include Damian Berardi, Althea Bock-Hughes, Alexander Terry, Lauren Drake and Grazyna Bozek from the University of Chicago.

    University of Chicago Medical Center

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