1. < Message from the Chair

As many of you know, the past year has challenged our ability as an academic department of medicine to fulfill our commitment to advance our research mission. Whether it is being at the leading edge of innovation and discovery or ensuring that we train and support the next generation of scholars, whose potential will ensure that creativity will continue to advance human health, the UCLA Department of Medicine (DoM) remains committed to fulfilling these missions despite the headwinds that we are facing. This week, I will highlight three examples of shining lights within the DoM that exemplify Leadership in Innovation that will Transform Care and Advance Health for all.

National Clinician Scholars Program Impact Report Highlights Excellence

The UCLA National Clinician Scholars Program (NCSP) is a two-year post-doctoral program that is designed to train physicians and PhD-prepared nurses to conduct high-impact research informed by clinical experience. The UCLA NCSP has produced a national cadre of LEADERS who have gone on to help shape health care policy, lead medical schools, run major community health organizations and direct impactful research programs across academic medicine, health systems, and government. Scholars who emerge from the UCLA NCSP fill a crucial need for clinician-scientists with the methods, credibility and leadership skills to generate evidence and guide health system transformation.

Dr. Walton’s research project during her time in the NCSP focused on how to strengthen the networks that support people with dementia. Despite the fact that 7 million people already live with Alzheimer’s disease and the growing prevalence of dementia as the population ages, our health care and community systems are not designed to fully support them.

“Even when families are deeply involved, they are often overwhelmed,” Dr. Walton said. “And many older adults have no available caregivers. By studying caregiver well-being, provider, and system-level factors, my goal is to identify meaningful ways to improve the quality and equity of dementia care.”

Dr. Walton feels that her participation in the NCSP has already profoundly shaped her career. She was able to build relationships with mentors across geriatrics, health services research and health policy, as well as with peers across the country who are connected to the NCSP nationally and its predecessor program, the Robert Wood Johnson Clinical Scholars Program.

“These relationships have helped me grow as a researcher and a leader,” Dr. Walton said. “The program has strengthened my ability to ask hard questions, pursue impactful research, and navigate the current funding landscape. I’m already doing the work I once hoped to do and am excited for what’s ahead.”

Dr. Zhang’s considers the UCLA NCSP to have been foundational for shaping her early career path. Its structured training and mentored research helped strengthen her qualitative and quantitative research skills, deepened her understanding of how health policy impacts health systems, and emphasized the importance of community-partnered research. Her experiences in the program influenced her research interests and her decision to pursue a doctorate in health policy and management at UCLA Fielding School of Public Health through the UCLA STAR program.

“The UCLA NCSP is a unique opportunity to learn with a truly wonderful, interdisciplinary group of co-fellows who are in a similar career stage and share a commitment to advancing the health and well-being of patients and communities,” Dr. Zhang said.

The UCLA Department of Medicine sponsored the work of both Dr. Zhang and Dr. Walton. This coming year, the recipients of our funding will be UCLA IM Residency Program graduate Cristina Valdovinos, MD, MPH; Victoria Chen, MD, who is joining us following her residency at Beth Israel Deaconess; and Beverly Kyalwazi, MD, a fellow in the UCLA Gastroenterology Fellowship Program who completed her residency at UT Southwestern Medical Center. These scholars, along with the rest of their cohort, will carry on a legacy of bridging gaps in health equity that without intervention, will only become wider with advances in technology.

“Equity isn't a side project of scholars in our program. It's embedded in how we train, in what we study and who we serve,” Dr. Elmore said. She noted that many UCLA NCSP fellows work in safety net settings during their time in the program and that their projects often involve the Greater Los Angeles VA Health System and Los Angeles County facilities.

"We want to train people that aren't just asking, ‘Does this work?’, but for whom, under what conditions and at what cost?” she said. “At a moment when AI is proliferating without adequate clinical input or rigorous evaluation, alongside burnout, workforce shortages, and mistrust, clinician-scientist leadership is not optional; it is essential.”

I would like to thank Dr. Elmore, the many faculty mentors who work with the UCLA NCSP, and our outstanding scholars for making this critical program so successful. You can learn more about this program and its impact through our profile of past and current scholars here. Applications for our next cohort open May 1, 2026, with a start date of July 1, 2027.

Body Processes Good Fats and Bad Fats Differently, Vallim Lab Finds

Bile Acids as Gatekeepers of Fat Absorption

Dietary fat is essential to survival, and humans have evolved to process it very efficiently. Bile acids are detergent molecules that help break fat into small droplets in the intestine, allowing fats to be efficiently absorbed into the systemic circulation. While this was quite useful for our ancestors living in times when food was scarce, this advantage becomes a disadvantage in a world where high-fat food options are readily available. The typical Western diet is high in fat, especially saturated fat — which is associated with inflammation and often implicated in metabolic disease. Other types of fat, monounsaturated and polyunsaturated fats, are known to protect the heart and liver but found less frequently in a Western-style diet. This study, led by co-first authors Alvin P. Chan, MD, PhD; Kelsey E. Jarrett, PhD; and Rochelle W. Lai, MS, RD, CSP, set out to better understand how bile acids regulate lipid absorption in metabolic disease.

Dr. Jarrett, an assistant project scientist in the Division of Cardiology, engineered a CRISPR tool to disable a critical enzyme for bile acid synthesis, CYP7A1. The tool successfully decreased bile acid levels by 50% in adult mice.

"I used some of the same delivery techniques that are being used for human gene therapies, but with the purpose of understanding new things about biology and nutrition,” Dr. Jarrett said. “Our first goal here was to decrease bile acid levels to see if fat absorption decreased. To do that I used gene editing in adult mouse liver to make an important bile acid gene nonfunctional."

While decreasing bile acids for the sake of decreasing fat absorption made sense, Lai, a dietitian who is working towards a doctorate in the UCLA Molecular, Cellular and Integrative Physiology program, questioned whether blocking fat absorption was truly novel. She proposed using a second group of mice to receive orlistat, an FDA‑approved weight‑loss drug (marketed as Alli) that blocks fat absorption in a mechanism distinct from decreasing bile acids to serve as a positive control. For eight weeks, each group of mice was fed a high-fat diet that mimics a Western diet — think greasy cheeseburger, fries, and a sugary soda. Although both groups absorbed less fat, only the mice lacking CYP7A1 were protected from weight gain.

Reducing Bile Acids Triggers GLP-1 Release

While the Cyp7a1 CRISPR mice ate the same amount as their controls, the orlistat group ate more. To see how the two approaches influenced absorption, the researchers used a technique called oxygen bomb calorimetry to analyze the caloric, or energy, content of animals’ fecal matter. Both the Cyp7a1 CRISPR mice and the orlistat-treated mice excreted more calories in their feces, but only the Cyp7a1 CRISPR mice did so without a compensatory increase in appetite.

The team was surprised that the mice without the CYP7A1 enzyme did not eat more and wondered if this mechanism could be leveraged to reduce obesity. To explore this further, they measured circulating levels of satiety-related hormones and found that GLP-1 secretion was markedly greater in the mice without CYP7A1 than in those on orlistat. After additional analyses suggested that GLP-1 release was being driven by fat absorption, the researchers examined where in the intestine the fat was being absorbed. Unlike control mice, Cyp7a1 CRISPR mice absorbed fat further down the digestive tract than normal.

“We think what’s happening is that as these fats travel further into the gut, they stimulate some receptors that promote the secretion of GLP-1,” Dr. Vallim explained. “That’s a way that your body tells your brain, ‘Hey, I’ve had enough of this nutrient.’”

How Absorption Shapes the Fats in Our Tissues

After establishing the link between bile acids, appetite, and fat absorption, the researchers investigated how altered fat absorption reshapes fat metabolism in the liver — the central hub for fat distribution — and other tissues. Through a combination of lipidomic analysis, histological examination and other techniques, they found that both bile acid reduction and orlistat treatment change what types of fatty acids end up in tissues, but to opposite metabolic ends. In Cyp7a1 CRISPR mice, the liver shifted toward higher levels of polyunsaturated “good” fats and lower levels of saturated “bad” fats. In contrast, orlistat broadly reduced fat absorption, including beneficial polyunsaturated fats. As a result, orlistat-treated mice activated liver pathways that generate new fats, a response that promotes metabolic dysfunction over time.

Next, the team asked whether changes in liver fat were driven by how different fats were absorbed, rather than by the mice simply eating less fat overall. By tracking the absorption of individual fatty acids, they found that Cyp7a1 CRISPR mice continued to absorb polyunsaturated “good” fats while allowing more saturated “bad” fats to pass into the stool—a pattern that matched what they saw in the tissues.

Singling Out Bile Acids

Given their findings so far, Dr. Vallim’s team then set out to elucidate the mechanism by which bile acids were changing fat absorption. As detergent molecules, bile acids transport fatty acids by wrapping them up in particles called micelles. The researchers hypothesized that some fats might simply be easier to put into micelles than others.

To test this idea, they took bile from mouse gallbladders and mixed it with individual fatty acids. The results validated what they had seen so far: Saturated fats took relatively large amounts of bile to dissolve, while unsaturated fatty acids required much less. The researchers then tested the same idea out with human bile, which has different bile acid composition. Using bile from an otherwise healthy patient following the removal of the gallbladder, they demonstrated that the mechanism was the same across species — saturated fatty acids required more bile to break down than unsaturated fatty acids, meaning that they were less readily absorbed. It was noteworthy that much less human bile was necessary to break down fatty acids compared to mice, suggesting that humans absorb fat more easily.

Dr. Vallim’s team next set out to understand how individual bile acids contribute to fat absorption. To do so, they used CRISPR targeting different enzymes involved in bile acid synthesis in a way that made the combination of bile acids similar to that of humans. After seeing the results, they then added different bile acids back in one at a time to see how they influenced fat absorption. The results showed that not all bile acids move fat equally. When the researchers removed an enzyme for the formation of a specific bile acid, called cholic acid (CA), saturated fat absorption was reduced, while unsaturated fats continued to be absorbed almost normally. Adding back the CA in diet confirmed its key role in saturated fat absorption.

Multi-Faceted Molecules, Multiple Absorption Approaches

Prior to this study, conventional wisdom held that all fat is absorbed in the same way through a largely passive, non-specific process. The team’s results show that fat absorption is far more selective than previously thought.

“This study really shows that different types of fats are being absorbed very differently, and specifically that polyunsaturated fat acids — the healthier fats — are actually absorbed more efficiently in the body,” Dr. Chan, a pediatric gastroenterologist and recent graduate from the UCLA STAR program, explained. “We show that this is due to bile acids and that by manipulating bile acids, you can manipulate absorption.”

Just as they found that not all fats are absorbed in the same way, the researchers also showed that not all bile acids are created equal.

“We often think of bile acids as a group of molecules, not that they each have their own specific physiochemical functions,” Lai said. “Seeing bile acids and absorption as multi-faceted molecules and processes adds novelty to our paper that previous research might not have put together.”

The researchers are preparing to submit two additional papers that detail their CRISPR and fat absorption methods. The team is also collaborating with other UCLA faculty to design small molecules that can target the bile acid-fat absorption pathway therapeutically to improve metabolic health.

“We think there is a lot of potential in targeting this system and maybe specific bile acids,” Dr. Vallim said. “We’re interested in pursuing all those avenues and, potentially, in developing new therapies.” 

Dr. Chan, Dr. Jarrett and Lai feel that the success of this large and complex project is a testament to their teamwork. They were grateful that Dr. Vallim fellow study lead Elizabeth J. Tarling, PhD, had the foresight to bring the three of them together.

“Because we came from different academic backgrounds and stages of training, each of us brought unique technical and scientific expertise that was required to move the project forward,” Dr. Chan said. 

Congratulations Thomas, Elizabeth, Alvin, Kelsey, Rochelle and the rest of the team on this groundbreaking study! I am hopeful that future work may lead to ways to block absorption of harmful fats, to improve metabolic health and prevent the many complications of obesity.

Michael K. Ong, MD, PhD Honored with National VA Research Award

I am proud to share that Michael K. Ong, MD, PhD was recently honored with the 2025 Field Leadership Excellence Award from the U.S. Veterans Affairs Office of Research and Development. This highly competitive accolade recognizes the accomplishments of research leaders within the VA — and with his exceptional leadership as the associate chief of staff for research within the VA Greater Los Angeles Healthcare System and as the Desert Pacific Healthcare Network (VISN 22) research officer, there is little question that this honor is much deserved.

Dr. Ong added that being a great leader is not about any single individual, but about the people one is leading.

“We have tremendous faculty, trainees, and staff who conduct research at our VA. I love being able to make sure their research is successful and thrives,” he said. “The history of medical research at our VA and at UCLA are closely intertwined. Success breeds success: successes in research at our VA directly translates into successes at UCLA, and particularly in our department of medicine. Our successes in basic science, clinical trials, and health systems research will ultimately lead to better health and outcomes for our patients.” 

This is the first time the VA has given an award for associate chiefs of staff for research. Dr. Ong was honored to be the inaugural winner alongside Dr. Keane, who is the longtime associate chief of staff for research at the Boston VA — the largest VA research program in the U.S. 

“I do want us to reclaim that title back from Boston,” Dr. Ong said. “This award says that the best two places right now to conduct research in a VA is here in Los Angeles and in Boston.” 

Congratulations, Michael! We are honored to work alongside you.

Dale

P.S.

I was in Jamaica this weekend to be with my mom who turned 91 yesterday. On Saturday I visited our ancestral homestead, which has been in our family for nearly two centuries, since emancipation from slavery in the 1830’s. This is where my paternal grandparents and great grandparents raised many children. My brother who is a surgeon has worked with members of the local rural community to restore the land for agricultural use, focusing on root crops, like Irish potatoes and sweet potatoes.

Pictures from the farm behind the house:

Another root crop that we eat in Jamaica. Do you know what root crop this is?

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