1. < Message from the Chair

As one of the leading medical schools in country, the David Geffen School of Medicine at UCLA continues to be recognized as being among the top tier for research and a leader in training primary care physicians. As many of you may be aware, not all medical schools participate in US News rankings now, which provides a perspective through which medical school ranking data should be interpreted. That said, we are proud of our accomplishments as a school, as recently articulated by our Dean, and importantly the contribution of faculty in the UCLA Department of Medicine (DoM) to our national standing.

This week, I will share some stories from the department that exemplify our influence as LEADERS in academic medicine and research, focusing primarily on examples of training and scholarship.

UCLA’s Christian Castro Named a Gilliam Fellow by the Howard Hughes Medical Institute, Recognizing Pioneering Research and Commitment to Equity in Science

I was delighted to learn that Christian Castro has been selected as one of 50 Gilliam Fellows by the Howard Hughes Medical Institute. This distinction recognizes Christian, along with his adviser Elizabeta Nemeth, PhD, for their outstanding research and commitment to advancing equity and inclusion in science.

Since joining UCLA in 2022, Christian has been working with Dr. Nemeth and Dr. Tomas Ganz, focusing on the molecular mechanisms of iron homeostasis. His current research explores how RNA biology intersects with mineral metabolism. “Iron is thought to be the catalytic factor for the evolution of life on Earth,” Christian explains. “Thus, understanding how RNA-binding proteins guide RNA molecules to maintain cellular iron balance is crucial for addressing iron-related disorders.”

As a fellow in the Gilliams Program, he will explore this uncharted territory with a hypothesis that RNA-binding proteins play a critical role in regulating iron homeostasis. His goal is to uncover unique RNA signatures associated with iron disorders which may lead to potential therapeutic targets within RNA-binding proteins. Christian adds, “the RNA-iron interplay remains largely unexplored, and my research aims to reveal new insights that could transform our approach to treating conditions like Alzheimer’s and cardiovascular diseases.”

As a first generation, immigrant, Latino scientist, the academic journey was shrouded in mystery. Mentorship has been critical in Christian’s success as a scientific investigator. He credits that success to the guidance and support of several scientists who helped him navigate the complexities of the scientific world. “Dr. Nemeth has been incredibly supportive and encouraging. Her patience and insight have been instrumental in refining my research and guiding me through my doctoral journey,” Christian shares. These experiences have not only propelled his scientific career but also inspired him to give back.

“I am deeply committed to using my personal journey and experiences to inspire and support other scientists. By sharing the challenges and successes I’ve encountered, I hope to provide valuable insights and encouragement to those navigating similar paths. It’s important to me to contribute to a supportive and collaborative scientific community where we can all thrive and advance together,” he concludes.

I extend heartiest congratulations to Christian on behalf of the DoM! We wish him well as he begins the Gilliam Fellowship Program and prepares to tackle his qualifying oral exam!

Minori Ohashi, MD, PhD Recently Appointed as a Butler Williams Scholars: Leading Advances in Stem Cell Research and Aging

Next, we celebrate Dr. Minori Ohashi, a dual trained geriatrician and stem cell biologist, who has been accepted into the prestigious Butler Williams Scholars Program. This achievement is a well-deserved reflection of her dedication and contributions to the field of stem cell aging with a focus on molecular and cellular mechanisms.

In the lab’s most recent study, Minori and her colleagues used exercise as a means of revitalizing the stem cell niche in skeletal muscle. They found that the greatest changes occurred in a populations of immune cells, known as macrophages. Minori therefore focused on the interaction between muscle stem cells and resident macrophages to find a way to improve the stem cell niche by modulating local macrophages to enhance the regenerative capacity of aged muscle stem cells. She also studies revitalization of aged skeletal muscle using partial reprogramming by inducing Yamanaka factors, which promote stem cell differentiation, as another anti-aging intervention.

Minori’s long-term research interests are to understand the molecular basis of aging and develop interventions that reverse cellular aging and restore youthfulness to attain healthy longevity. She is particularly interested in studying tissue regeneration and organismal aging using adult stem cells as a model system. Minori’s clinical work, caring for many older adults with progressive geriatric syndromes that lack effective treatment, further motivates her to uncover the underlying molecular mechanisms of aging to advance toward potential cures.

Pamela Mattar, PhD and Rajat Singh, MD, MBBS, “Insulin and leptin oscillations license food-entrained browning and metabolic flexibility,” Cell Reports

Drs. Pamela Mattar and Rajat Singh recently reported a fascinating discovery on how fasting impacts insulin and leptin oscillations. Obesity and metabolic diseases are significant public health concerns, often caused by overeating. Their study found that feeding two meals in a 24-hour period leads to feeding-driven surges in levels of circulating insulin and leptin. These programmed oscillations of insulin and leptin lead to marked genetic, functional, and metabolic remodeling of subcutaneous white adipose tissue (sWAT), resulting in increased energy expenditure and weight loss. This remodeling of sWAT is driven by recruitment of specific immune cells, the innate lymphoid type 2 (ILC2) cells to sWAT. They also found that innervation of sWAT is crucial for this remodeling, since denervation of sWAT blocks resolution of adipose tissue inflammation and weight loss.

This is critical information as hormones that respond to changes in nutrient availability, such as insulin and leptin, have been extensively studied. However, how changes in their oscillation patterns in response to intermittent feeding/fasting and their relevance to obesity and energy expenditure were not known. These findings reveal that restricting feeding windows across the circadian period greatly improves insulin and leptin sensitivity, which is required for adipose tissue remodeling and energy expenditure.

These animal studies suggest that organizing meals that allow for two large fasting windows each day, could be beneficial. They note that “Adipose tissue is not only a site to store fat but can also be induced to burn fat if regular fasting intervals are included in one’s lifestyle.” They further emphasize that “meal-driven insulin and leptin surges are required for weight loss and metabolic benefits.”

Angela Leung, MD, MSc and Connie M. Rhee, MD, MSc, “Risks of Iodine Excess,” Endocrine Reviews

Another indication of our faculty’s reputation is when they are invited to write authoritative reviews in major journals. Thus, I was pleased to see that Drs. Angela Leung and Connie M. Rhee, two long-time collaborators with an interest in the intersection between thyroid and kidney disease were invited by Endocrine Reviews to provide an in-depth review exploring the overlap between iodine handling and thyroid disease.

Iodine is a micronutrient that is required for the normal production of thyroid hormone. It is well-established that exposure to or ingestion of excessive iodine is associated with an increased likelihood of thyroid dysfunction (hypo- or hyperthyroidism). In this narrative review, Drs. Leung and Lee provide a historical overview and update on the current understanding of thyroid risks following iodine excess, as well as potential subsequent thyroid dysfunction-associated heart disease and mortality arising from an acute iodine load.

They note that high amounts of iodine are commonly encountered in medical settings. For example, radiology studies often require iodinated contrast dye, and iodine-rich medications like amiodarone are frequently medically indicated. Being cognizant of which patients might develop thyroid dysfunction upon exposure to too much iodine is impactful to care.

They add, “Although physiologic adaptive mechanisms are in place, it is important to be aware of the risk factors that may predispose one to the adverse thyroid effects of excess iodine exposure and intake.”

Anna H. Lee, MD and Lin Chang, MD, “Role of Sex, Anxiety, and Resilience in the Association Between Adverse Childhood Experiences and Irritable Bowel Syndrome,” Clinical Gastroenterology and Hepatology

Next, we turn the spotlight on Drs. Anna H. Lee and Lin Chang whose recent work explored how a history of adverse childhood experiences (ACE) increased the odds of having irritable bowel syndrome (IBS) in both women and men. While ACE are known to increase IBS risk in women, their study is the first to describe this risk in men, which should be considered when treating patients with a history of ACE.

The researchers found that although women have more ACE and IBS overall, both sexes with a history of ACE are vulnerable to having IBS. They add that the risk of IBS is increased with ACE in both men and women, particularly in those who had a household member with mental illness. However, factors like anxiety, and to a lesser extent, decreased resilience may mediate this relationship between IBS and ACE. They explain that understanding these factors can help to guide management, e.g., institute an integrated, multidisciplinary approach rather than solely targeting GI symptoms.

The researchers note that this elevated risk of IBS may, in part, be due to anxiety and decreased resilience, which have previously been shown to be worse in patients with IBS and are potential therapeutic targets.

Ira Kurtz, MD, “Data-driven prediction of continuous renal replacement therapy survival,” Nature Communications

In the latest study from Ira Kurtz, MD, Chief of the UCLA Division of Nephrology, he explores how integrating machine-learning models into healthcare can improve patient treatment outcomes and resource management for clinicians. The study focuses on a type of dialysis called Continuous Renal Replacement Therapy (CRRT), which is a gentler therapy used for very sick hospitalized patients who cannot handle regular hemodialysis. CRRT is often used as a last resort, but many patients do not survive it, leading to wasted resources and false hope for families. To help doctors decide whether a patient should start CRRT, Kurtz and colleagues developed a machine-learning model. This model uses data from thousands of patients' electronic health records to predict their chances of surviving CRRT. By making these predictions more accurate, the model aims to improve patient outcomes and resource use, by serving as a basis for testing its utility in future clinical trials.

E. Dale Abel, MD, PhD, “Diabetes mellitus—Progress and opportunities in the evolving epidemic,” Cell

As we look to the future of diabetes treatment, we see great promise in new therapeutics. These include using stem cells to replace the loss of insulin secreting cells in type 1 diabetes, to groundbreaking treatments that may prevent development of the disease altogether. We explore how precision medicine approaches will allow us to better tailor therapies to individual patient profiles, leading to better health outcomes. The perspective discussed the future uses of GLP1RA combinations that have proven efficacy in diabetes, and growing indications for other disorders such as obesity, sleep apnea and heart failure and potential indications in neurodegenerative disorders such as Alzheimer’s disease.

Dale

P.S.

From time to time, I am asked if we are now settled in Los Angeles. I think we officially are Angelinos now… as I received my first jury duty summons.

And fulfilled it!!

In case you are wondering, Evan is my first name, but my parents always called me via my middle name (Dale).

---