Lab Notes

Summaries of late-breaking research and news from the scientists at UCLA Health and David Geffen School of Medicine

Hope for a highly lethal brain cancer A study led by Dr. Linda Liau finds a cancer vaccine co-developed by Dr. Liau at UCLA led to meaningful increases in survival for patients with glioblastoma multiforme (GBM), a highly lethal brain cancer with a nearly 100% recurrence rate and dismal patient survival. Glioblastomas are aggressive and rapidly lethal; there is a pressing need for new treatments and for novel clinical trial designs to streamline their development. This phase 3 nonrandomized controlled trial of 331 patients found newly-diagnosed GBM patients who received DCVax-L had a median overall survival of 19.3 months after randomization (22.4 after from surgery) compared to 16.5 months survival among a group of external control patients treated with standard care.  For patients with recurrent GBM, median overall survival was 13.2 months from relapse in the DCVax-L group vs 7.8 months in the external control cohort. Meaningful increases in the long-term tails of the survival curves in both nGBM and rGBM were also observed. Read the study in JAMA Oncology and hear Dr. Liau discuss its results and implications in this JAMA podcast.

UCLA Health's response to unaccompanied children at the border A new report details the University of California Health (UCH) system-wide, rapid response to the humanitarian crisis of unaccompanied children crossing the southern U.S. border in the midst of the COVID-19 pandemic in 2021.  In collaboration with multiple federal, state, and local agencies, UCH mobilized a multidisciplinary team to deliver acute general and specialty pediatric care to unaccompanied children at two Californian emergency intake sites. The response, which did not disrupt normal UCH operations, mobilized the capacities of the system and resulted in a safe and developmentally appropriate environment that supported the physical and mental health of migrant children during this traumatic period. Overall, 260 physicians, 42 residents and fellows, four nurse practitioners participated as treating clinicians and were supported by hundreds of staff across the 2 sites. Over five months and across both sites, a total of 4,911 children aged 3–17 years were cared for. A total of 782 children had COVID-19, most infected prior to arrival. Most children (3,931) were reunified with family or sponsors. Read more in the Nov. 15, 2022 report in Academic Medicine.

When congenital heart disease patients get cancer: A new study of cancer outcomes in people with adult congenital heart disease (ACHD) indicates the need for more concerted efforts to appropriately screen and care for this unique population. This collaborative study from the UCLA Adult Congenital Heart Disease and cardio-oncology programs found that all cardiac events in this population were able to be addressed successfully without permanent discontinuation of cancer therapy. In this cohort of adults with both conditions, the median age of cancer diagnosis was only 43.5 years. Only 10% of cancers were detected through screening, and a quarter of all patients had metastatic disease at time of diagnosis. Despite predominantly moderate or great anatomic complexity of congenital heart disease and a high incidence of adverse cardiac events, most deaths occurred due to cancer rather than cardiovascular causes. The authors say the data shows that it is feasible to administer systemic cancer therapy to such a cohort and manage cardiotoxicity without prolonged discontinuation of therapy. Additionally, the authors underscore the need to better define cancer screening in this high-risk population to ensure timely diagnosis and improved outcomes. Read the study in Cardio-Oncology.

Diversity in Gastroenterology A new survey of more than 1,200 gastroenterology (GI) and hepatology professionals in the United States assessed current perspectives of racial and ethnic workforce diversity and health care disparities. It finds the most frequently reported barriers to increasing racial and ethnic diversity in GI and hepatology were insufficient representation of underrepresented racial and ethnic minority groups in the education and training pipeline (reported by 35.4% of respondents), in professional leadership (27.9%), and among practicing GI and hepatology professionals (26.6%). The survey also underscored the discrepancy in satisfaction with workplace diversity among GI and hepatology physicians by race and ethnicity. While 63% of Black physicians were very or somewhat unsatisfied with workplace diversity, 78% of white physicians were very or somewhat satisfied. Read the study in the December 2022 issue of Gastroenterology.

An unexpected Alzheimer’s discovery Little is known about how non-neuronal brain cells known as astrocytes – distinguished by their “bushy” star-like shape – differ in structure or function across the brain, or how these cells may contribute to neurological disease. In a new UCLA-led study aimed at better understanding the molecular similarities and differences between astrocytes, researchers found gene networks correlated with the cells’ shape unexpectedly contained Alzheimer’s disease risk genes. When researchers working with mice reduced the expression of key genes related to the cells’ shape in the hippocampus, making the astrocytes less complex, cognitive function was reduced. They also found the expression of the same genes was reduced in human brains of Alzheimer’s patients. The findings suggest that therapies restoring astrocyte structure may help fight Alzheimer’s. The study was led by Fumito Endo, a project scientist in the lab of UCLA professor of physiology and neurobiology Baljit Khakh. Read the Nov. 4, 2022 study in Science.

Environmental risk of neurodegeneration While scientists increasingly recognize long-term exposure to air pollution as contributing to the development of neurodegenerative diseases like Parkinson’s and Alzheimer’s, how this exposure increases the risk is not well understood. A new UCLA study of air pollution exposure in a novel animal model found that the exposure caused neuronal loss, which was at least partly due to a buildup of protein aggregates in the brain. The researchers, led by Dr. Jeff Bronstein, director of the Movement Disorders Program at UCLA, also found that pollution exposure activated inflammatory cells that can be both good and bad, indicating that any medications to combat inflammation should be highly targeted to cells that can damage neurons. Read the study in Scientific Reports

Housing & Health: It's complicated Previous evidence has shown that housing insecurity—that is, difficulty with housing affordability and stability—is prevalent and results in increased risk for both homelessness and poor health. But a new study finds weak evidence that interventions to boost housing affordability and stability make a difference in improving health. Led by Dr. Katherine Chen, health sciences clinical instructor at the David Geffen School of Medicine at UCLA, the authors conclude that existing strategies to prevent housing insecurity, while necessary, are not sufficient to achieve long-term health gains for vulnerable populations and may need to be both modified and partnered with other policies to redress social inequity, including racism in housing. Read the study in the Nov. 2, 2022 issue of JAMA Network Open

Immunotherapy attaching to cancer cells

New approach to bladder cancer A new UCLA-led study of 82 patients with a high-risk form of bladder cancer shows that 71% of the patients, all of whom had not responded to typical therapy, responded to an experimental immunotherapy drug called NAI, which works by activating the body’s natural killer cells. After two years, 90% of the patients who responded to the drug avoided surgery to remove the bladder and there were no deaths from bladder cancer among all 82 patients. The study was funded by ImmunityBio and the results appear in the Nov. 10, 2022 issue of  NEJM Evidence.

Handheld diagnostic tool

A lab in the palm of your hand Using swarms of pinhead-sized magnets inside a handheld, all-in-one lab kit, UCLA researchers have developed a technology that could significantly increase the speed and volume of disease testing, while reducing the costs and usage of scarce supplies. Read more in this Nov. 10, 2022 press release from the UCLA Samueli School of Engineering here.

Do celebrity endorsements increase vaccination? In the year between October 2020 and October 2022, Americans’ willingness to be vaccinated (defined as being vaccinated or planning to be) increased from 47.6% to 81.1%. A new survey led by Arash Naeim at the Center for SMART Health at UCLA’s Clinical and Translational Science Institute looked at how much impact five strategies had on increasing the willingness of unvaccinated adults to get their shots. It found endorsements by members of the scientific community, healthcare professionals, or celebrities had no positive effect. What did? The chance to relax the need for masks and social distancing, financial incentives, and vaccine requirements for attending sporting events traveling and work. Read the study in Vaccine.

Award winner Roni Haas

Young investigator award October 26, 2022: Roni Haas, PhD, postdoctoral scholar in the lab of Paul Boutros has received a 2022 Young Investigator Award from the Prostate Cancer Foundation. The award will support Haas’s prostate cancer research project, Associating Germline Variants with Prostate Tumor Evolution and Lethality, at total of $225,000 over three years. Read more about the PCF Young Investigator Awards here.