Year 4. November 3.
[INTRO]
Jingran Ji, MD Receives GEMSSTAR Grant to Study Physical Function in Patients with Gastroesophageal Cancer
I am pleased to share that Jingran Ji, MD, a Santa Monica-based hematologist-oncologist and a first-year clinical instructor in the hematology-oncology division, recently received his first NIH grant. He will use the award — a Grants for Early Medical/Surgical Specialists' Transition to Aging Research (GEMSSTAR) (R03) grant from the National Institute on Aging — to learn how to treatment for gastroesophageal cancer, a type of cancer that begins in the esophagus and stomach, affects physical function in older adults.
“I felt incredibly fortunate and grateful that the NIA recognized the importance of our proposed work,” Dr. Ji said. “This support also reassured me that the university remains deeply committed to helping junior investigators like myself develop the skills to conduct high-quality, independent research.”
Dr. Ji’s study will build the infrastructure to track patients with gastroesophageal cancer throughout their treatment journey to objectively measure changes in physical function and quality of life. The goal of the study is to understand the extent of physical function decline and and identify risk factors for decline before and during treatment. The study will include virtual visits to collect objective and self-reported measures of physical function and home collection of blood samples throughout treatment. The team will also study the lived experiences and challenges patients face in maintaining their quality of life and function while undergoing treatment.
While improved therapies have extended the lives of older adults with gastroesophageal cancer, there is not yet robust data on how these therapies impact patients’ independence and physical function. Understanding these effects will help oncologists make more informed treatment choices and will guide the development of interventions that can prevent and reverse the adverse effects of treatment.
“I hope the findings from this study will guide more patient-centered treatment decisions that reflect the values and priorities of older adults,” Dr. Ji said. “Ultimately, I envision this work serving as a foundation for developing mechanism-based interventions that preserve or restore physical function in this vulnerable and rapidly growing patient population."
Dr. Ji’s mentor Mina S. Sedrak, MD, MS feels that Dr. Ji’s curiosity, rigor and compassion reflect the best of what we strive to cultivate in the UCLA Department of Medicine (DoM) research faculty. Dr. Sedrak himself received a GEMSSTAR award nearly a decade ago and recalls how transformative it can be for early-career investigators.
“Watching Dr. Ji’s growth as a physician–scientist dedicated to improving the lives of older adults with cancer has been deeply rewarding,” he said. “I’m so proud of him and grateful to have the chance to mentor him through this journey — one that will undoubtedly shape his career and, more importantly, the future of cancer and aging research.”
Dr. Ji feels that Dr. Sedrak’s dedication, insight, support and generosity with his time have been instrumental to Dr. Ji’s growth as a physician-scientist. He believes that UCLA and the DoM offer an exceptional environment for the kind of work his GEMSSTAR grant supports because of their high, diverse volume of patients with gastroesophageal cancer and the cutting-edge treatments available through the division of hematology-oncology.
“The DoM also has a clear mission to foster young physician scientists, promote academic discovery, and support research aimed at improving the lives of our patients — especially in areas that are not typically funded by industry,” Dr. Ji said.
Please join me in congratulating Dr. Ji on this tremendous step in his career!
Estelle M. Everett, MD Uses Natural Language Processing Algorithm to Identify Diabetes Tech Use in Electronic Health Records
Insulin pumps and continuous glucose monitors (CGMs) can dramatically improve outcomes for people with type 1 diabetes. However, the people who typically have poorer outcomes with diabetes typically have lower access to these life-changing technologies. Health services research like the work conducted by Estelle M. Everett, MD is crucial to improving the health of these populations. On Sept. 29, she and her team published an article in “Diabetes Technology and Therapeutics” detailing how they created and tested a natural language processing (NLP) algorithm to identify the use of insulin pumps and CGMs in patients’ electronic health records (EHRs), a tool that could improve research efficiency and ultimately patient care.
“Understanding who uses diabetes technologies in real-world settings is key to improving care and outcomes. Our algorithm provides a scalable way to identify device use from EHR data, which has potential applications in population health, clinical research, and quality improvement efforts,” Dr. Everett said. “This can help clinicians and health systems better understand where technology is being used and where there may be opportunities to improve access and support.”
To create the algorithm, Dr. Everett and her team reviewed a random sample of endocrinologists’ notes from an outpatient clinic and catalogued how insulin pump and CGM use was documented. They used the patterns they detected to build and refine rule-based NLP algorithms, then evaluated them on a set of the most recent notes in the EHRs of 667 UCLA patients. They then externally validated the algorithms in a second health system with a different EHR and patient population. In all cases, they compared the algorithms’ performance to manual chart review and assessed their sensitivity and specificity. They also compared the algorithms to the accuracy of billing codes for insulin pump and CGM use within the same UCLA dataset.
The results showed that the final algorithms were highly sensitive and specific. Billing codes were less accurate in comparison.
Next, Dr. Everett and her team will expand the algorithm to capture more nuanced aspects of technology use. For instance, it will be able to distinguish between active, former and intermittent users, and will integrate these data with clinical outcomes.
“This will allow us to better understand how diabetes technology use evolves over time and how it impacts clinical outcomes,” Dr. Everett said. She feels that the UCLA DoM is the right place to conduct this research because of its collaborative environment with the strong expertise, resources and infrastructure to support innovative, data-driven research. Its cross-discipline partnerships, such as the one it holds with the UCLA CTSI bioinformatics team, “provides invaluable support for developing and implementing advanced analytic methods such as this one,” she added.
Dr. Everett would like to thank her mentors, Tannaz Moin, MD, MBA, MSHS and Alex Bui, PhD, as well as the medical student on her team, MS4 Ryan Tiu, for her integral contributions to the project, noting that her dedication and insight were essential to the success of their work. Congratulations to Dr. Everett and the rest of the scientists behind this project!
mRNA from Blood May Indicate Endothelial Damage and Worse Outcomes in ARDS
Acute respiratory distress syndrome, or ARDS, is the most severe form of respiratory failure — with nearly 50% mortality in the most serious cases — and is a potential complication of COVID-19. Despite more than 50 years of research, there are few therapeutic strategies to turn it around once it has begun, a problem that arises in part because researchers still do not know exactly which forms of the condition are treatable.
To initiate the development of new therapies for ARDS, researchers across several divisions in the UCLA DoM collaborated with scientists at the University of Southern California, the University of California – San Francisco, Boston Children’s Hospital, Harvard Medical School and many more institutions to learn whether the presence of mRNA usually found in endothelial cells can be used to predict a patient’s likelihood of severe outcomes from ARDS. The results of their work so far were published on Oct. 14 in “Critical Care.”
“As a field, there is a concerted effort to identify treatable phenotypes and endotypes within this syndrome. Our lab is focusing on how measurements of endothelial damage can identify a subtype of ARDS that may be best suited for targeted therapies,” Ana C. Costa Monteiro, MD, PhD, a UCLA pulmonologist and first author of the article, said. Dr. Costa Monteiro is a collaborator with the lab of Hrishikesh Kulkarni, MD, MSCI and an affiliate of the lab of Anil Sapru, MD, two of the paper’s senior authors.
Why endothelial mRNA? The lungs are the largest reservoirs of endothelial cells, the main type of cell that lines blood vessels. If there is damage to them, levels of endothelial mRNA will rise.
“We identified that higher circulating levels of endothelial signature, a surrogate for endothelial damage, is associated with worse respiratory outcomes and mortality in both children and adults with or at risk for ARDS,” Dr. Monteiro said. Her team did so by analyzing clinical data and blood samples from pediatric and adult patients who were hospitalized with COVID-19 and received mechanical ventilation; they studied the samples using a technique called deconvolution analysis. Biological samples were collected at three-month intervals up to 12 months after they were discharged from the hospital; clinical mortality data was assessed through day 28.
Next, the group behind the study wants to confirm whether the endothelial cells they identified are indeed from the lung vasculature, determine what physiological pathways within pulmonary endothelial cells are disrupted in ARDS and see if they can identify a concise panel of genes within the cells that can be used as a prognostic tool for patients at risk from ARDS.
The faculty in the pulmonology division at UCLA are instrumental to making that challenging to-do list possible, Dr. Costa Monteiro noted.
“We have world renowned physician scientist in our department willing to collaborate with and support junior faculty, and leadership supporting research efforts and collaboration,” she said.
Thank you to Dr. Costa Monteiro, the Kulkarni lab and all of the DoM members who took part in this important project for your outstanding work!
April W. Armstrong, MD, MPH Leads UCLA Arm of Clinical Trial on Potential Psoriasis Breakthrough
There are highly effective treatments for moderate to severe plaque psoriasis, but most of them require routine injections that limit their use. The results of phase 3 clinical trials conducted in part at UCLA under the leadership of April W. Armstrong, MD, MPH suggest that a new once-daily oral medication, icotrokinra, is safe and effective. The trials were sponsored by Johnson & Johnson.
“For patients, this represents a potential breakthrough,” Dr. Armstrong said. “This could transform access, adherence, and quality of life for individuals living with psoriasis."
Icotrokinra is a peptide that works against psoriasis by binding the interleukin-23 (IL-23) receptor. In the trials, it was compared to placebo or to another oral psoriasis drug, deucravacitinib, that inhibits the enzyme JAK-1.
The trials, called ICONIC-ADVANCE 1 and 2, were described in an article published Sept. 27 in “The Lancet.” They took place across 13 countries at 149 sites, including UCLA, and involved more than 1400 patients. Subjects were broken up into groups and randomly assigned to take icotrokinra, deucravacitinib, or a placebo for at least 26 weeks. Those who were on deucravacitinib or a placebo were switched to ikotrokina at week 16 or week 24. The primary endpoints were the proportion of participants who achieved grade 0 or 1 (clear or almost clear) skin by week 16, with at least a two-grade improvement and 90% improvement in psoriasis area and severity index (PASI), a way to measure the severity of psoriasis. More than two-thirds of patients achieved clear or almost clear by week 16, with a safety profile comparable to placebo.
As the drug makes its way to patients, Dr. Armstrong and her team will follow up long-term to assess durability and safety; conduct biomarker analyses to identify responders; and perform real-world implementation studies to understand how oral IL-23 blockade can best fit into routine care. They are also exploring icotrokinra’s potential in other inflammatory skin diseases, like hidradenitis suppurativa and atopic dermatitis.
"UCLA’s Department of Medicine offers the ideal environment for this work,” Dr. Armstrong said. “We combine a supportive clinical trial infrastructure, diverse patient populations, and a collaborative translational research culture that bridges discovery and patient impact. The Department’s commitment to research ensures that advances like this move swiftly from bench to bedside, improving outcomes for patients everywhere."
Please join me in congratulating Dr. Armstrong and the rest of the investigators on these impressive results. I look forward to seeing how this medication improves patient lives.
Modlin Lab’s Study on Antimicrobial Responses in Leprosy Makes JCI Cover
Hansen’s disease — also known as leprosy, one of humanity’s oldest infectious diseases — serves as an excellent model for how the body responds to infection. For the past 40 years, distinguished professor of medicine Robert L. Modlin, MD has been using the bacteria that causes Hansen’s disease, Mycobacterium leprae, to study the immune response. Their work made the cover of the Sept. 2 “The Journal of Clinical Investigation” (JCI), in which the team published the results of a study on what are known as “reversal reactions”, a phenomenon where the immune system spontaneously clears leprosy-causing bacteria.
There are two main types of leprosy; in both types, “the clinical spectrum mirrors the immune response,” Dr. Modlin said. Tuberculoid leprosy is typically the milder form, with fewer lesions and characterized by a strong immune response wherein cells called T-cells destroy the bacteria and lesions heal on their own. On the other hand, in lepromatous leprosy, there are widespread lesions filled with M. leprae-infected white blood cells. In this case, the immune response is making antibodies to the bacteria but do not eliminate it.
“You're able to study why some individuals can make the appropriate host defense response, the T-cell response, to eliminate the bacteria, and others can't — they make an antibody response that doesn't kill the bacteria,” Dr. Modlin explained. However, some patients experience reversal reactions, where their type of leprosy essentially “upgrades” from lepromatous to tuberculoid leprosy because the immune system suddenly is able to remove the bacteria.
"We wanted to ask, ‘What are the dynamics of that? What is the mechanism?’” Dr. Modlin said.
To find out, first author Priscila R. Andrade, PhD and other members of Modlin’s team used RNA sequencing to study skin samples from patients with leprosy at the Oswaldo Cruz Foundation in Rio de Janeiro before and after they experienced reversal reactions. They identified more than 60 antimicrobial peptide-encoding genes that become active when the immune response shifts. Further experiments showed that four peptides the genes encoded — S100A7, S100A8, CCL17, and CCL19 — directly killed M. leprae, even to the point of being more effective than the antibiotic rifampin.
The team was able to witness this up close with the help of electron microscopy, which gave them the image that became the journal edition’s cover art. Though the original image was black and white, he used ChatGPT to change the color and match JCI’s style.
"Seeing the image accepted as the cover was thrilling,” he says. “It visualizes what we have been trying to understand for years — how human immune mechanisms can kill these persistent pathogens."
Characterizing the mechanism behind reversal reactions opens the door to new insights into conditions caused by similar bacteria. His team is also studying tuberculosis and hopes to apply the findings from the lab’s latest work to that context as well.
“By learning how patients’ immune systems to kill M. leprae, we can begin to design treatments and vaccines that harness these same mechanisms against leprosy, tuberculosis, and beyond,” he said.
Please join me in congratulating the Modlin lab on this fantastic work!
Andre Nel, MD, PhD and Team Featured in Scientific American for Peanut Allergy Nanoparticle
Peanut allergies are among the most common and dangerous food allergies in children. While treatments that aim to establish tolerance, such as oral immunotherapy, may be partially successful, breakthrough failures can be deadly.
A nanocarrier drug delivery system from the laboratory of Andre Nel, MD, PhD, chief of the UCLA Division of NanoMedicine and research director of the California NanoSystems Institute (CNSI), appears to circumvent some of the problems associated with other immunotherapies for peanut allergy by using mRNA to alter a liver-based regulatory T cell response to peanut allergens. Their therapy was featured by the prestigious science publication “Scientific American” in September as part of a story on peanut allergy treatments and is currently being prepared for clinical trials by a start-up spun out of CNSI. It is also being applied to other autoimmune conditions, such as type 1 diabetes.
The science behind Dr. Nel’s team’s approach is an application of profound progress in our understanding of how the immune system regulates itself, including drawing on its immune tolerance capability that is targetable by mRNA nanoparticle technology (developed for COVID vaccination). Just last month, the 2025 Nobel Prize in Physiology or Medicine was awarded to three immunologists who discovered regulatory T cells, which prevent the immune system from attacking itself by turning off a specific response while leaving the protective part of the immune response intact. One of the recipients was Fred Ramsdell, PhD, who studied the cells while earning his PhD here at UCLA.
Thanks to advances in mRNA technology beyond infectious disease applications, the scientists working under Dr. Nel were able to make use of previously untapped discoveries about protective pieces or epitopes in the peanut allergen, capable of inducing suppressive or tolerogenic immune responses, instead of turning the allergy on.
“Unfortunately, in most attempts to date, researchers developing immunotherapies for peanut allergy did not sort the injury-inducing epitopes in peanut allergens from the tolerogenic or immune-suppressive epitopes,” Dr. Nel explained. “Our therapy uses only the immune suppressive T cell epitopes, which comes from 30 years of research revealing the immune suppressive potential of these epitopes due to their ability to activate regulatory T cells.”
Prior to the advent of mRNA technology at scale, scientists attempting to leverage the regulatory T cell response to prevent peanut allergy by making use of individual peptides for an attempted vaccination approach to peanut anaphylaxis. Unfortunately, that approach turned out not to be practical due to differences in peptide solubility, interfering in proper delivery the immune system. However, transforming these epitopes into minigenes that can be linked together into a single mRNA strand, allowed the nanomedicine team to place the entire epitope repertoire into a nanoparticle that is targeted to the liver. This organ is a specialized site for training of long-lived regulatory T cells, allowing the team to reconstitute a potent vaccine, capable of suppressing peanut anaphylaxis for a long time in their preclinical model.
A 2023 study in mice demonstrated that Dr. Nel’s team’s nanoparticle is effective at preventing the most serious consequence of peanut allergies — anaphylaxis — in animal models. A biotech startup has been developed around the product through the CNSI Magnify incubator, and it is now in the process of undergoing the necessary tests for an investigational new drug application with the FDA. It is also being studied in other contexts: At Research Day last month, Dr. Nel’s team shared a poster showing that the same technology can be used to create a treatment that is 100% effective in preventing the development of type 1 diabetes in mice. Recently, the invention was also be applied against other food allergies in animal models, as well as finding an alternative way to reprogram the liver’s deficient immune response against metastatic cancer cells, with the ability to avert a frequent lethal outcome.
While Dr. Nel cautioned that use of the therapy in patients with peanut allergies is still a way off, he hopes it will be ready for a clinical trial in a few years.
“I don't want to make any false promises, but we are hopeful and committed to our end goal, and want to see it sooner rather than later,” he said. He noted that he is grateful to the UCLA DoM for its support of his work and to CNSI, which has helped launch many California biotech companies, working to solve serious challenges in medicine and saving patient lives. These advances were celebrated at CNSI in October 2025 with Gov. Gray Davis, who highlighted the research and economic contributions that CNSI made to California’s economy over the last 25 years.
Please join me in celebrating the progress of Dr. Nel’s team and their highlight in Scientific American!
Ashley Stein-Merlob, MD, PhD Honored with Young Investigator's Award by International Cardio-Oncology Society
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