Year 4. August 11. Research Central to our Department’s Missions
The month of August has been a very challenging one for many of our research colleagues who have lost significant amounts of their federal research funding as a consequences of the suspension of many federally funded research grants to UCLA, in response to allegations against the University by the Department of Justice. (Link to Chancellors original and subsequent emails, as well as to the message from UC President Milliken). The total cost of the suspended grants to UCLA are approximately $600M, and in the UCLA Department of Medicine (DoM), the total value of suspended awards, should they not be reinstated is $112M. These grant dollars, in addition to supporting faculty salaries and those of their trainees and staff, covered the cost of essential research projects in many areas that seek to advance and improve human health. The department is working actively to devise ways to support our impacted colleagues. We have stated our commitment to impacted junior faculty and trainees and the plans that we will be taking to minimize the impact on faculty salaries. We have shared our approach, with division leadership and in various communications to our research faculty and are planning a Town Hall later this week with impacted faculty to discuss our plans and to hear their concerns. We will also be meeting individually with affected investigators to work out how best to support the critical aspects of their missions, while adjusting to the reality that it will not be possible in the short term to fully substitute for the sudden and catastrophic loss of funding. Our department has multiple missions, spanning clinical and educational excellence, research and community engagement. Thus, there are many in the department who will not be directly impacted by the recent challenges that our research colleagues are currently experiencing. It is important to emphasize here, that we are one department of medicine and collectively we will rise to and overcome this challenge. I encourage you to show our impacted colleagues some love and support as we work together to get through this challenging time.
This week, I planned to highlight examples of the important research contributions that some of our faculty have made, and the recent events make this even more imperative to do so. Our research contributions are saving lives, advancing knowledge and leading innovations that will transform care and advance health for all.
Our endocrinology division is one of the best in the world. This week we highlight scientific advances from faculty in Divisions of endocrinology and General Internal Medicine and spotlight our LEADERS' contributions to the Endocrine Society's annual conference.
Studies by Melissa G. Lechner, MD, PhD Could Improve Endocrine Side Effects from Cancer Immunotherapy
Our researchers in the UCLA Division of Endocrinology work on the leading edge of science. This is exemplified by the work of Melissa G. Lechner, MD, PhD, an endocrinologist who studies how a type of cancer treatment called immunotherapy impacts the endocrine system. Dr. Lechner recently led two studies that pave the way for major developments in the care of patients with cancer — one with important implications for treating patients with osteoporosis and breast cancer and another that could lead to a new treatment to prevent serious endocrine side effects of immunotherapy.
A report describing the first recent study — which was conducted in collaboration with City of Hope — was published June 23 in the journal The Oncologist. In it, she and her team sought to learn whether a class of osteoporosis drugs known as bone-modifying agents (BMAs) might interact with cancer medications called immune checkpoint inhibitors (ICPIs) in a way that increases the risk of side effects related to the immune system, which range from somewhat milder reactions like rashes to more severe ones like hepatitis and arthritis. Dr. Lechner’s team conducted a clinical trial that included 425 women who were treated with an ICPI for breast cancer; 55 of them also received the drug denosumab (Dmab) for osteoporosis, 31 were treated for osteoporosis with zoledronic acid (ZA) and 339 did not receive any BMA.
The results showed that BMAs, particularly Dmab, seemed to make ICPIs more effective while also raising the risk of side effects. While the trial is still ongoing, Dr. Lechner noted that clinicians should be aware of these interactions when they counsel patients about the risks and benefits of breast cancer.
“A patient who has very advanced cancer may accept that risk,” Dr. Lechner said. “By contrast, we now use immunotherapy in patients with relatively early-stage breast cancer, just as an adjuvant therapy. In a circumstance where the patient is likely to have a very good outcome anyway, thinking about that risk-benefit ratio is important.”
In the second study, an article on which was published July 8 in JCI Insight and covered by UCLA Health, Dr. Lechner and her team set out to learn if a class of anti-inflammatory medicines called JAK inhibitors (JAKis) could prevent ICPI-induced type 1 diabetes (T1D) — a rare but serious side effect — without dulling the immune system’s capacity to fight cancer. To do that, they used a mouse model and patient samples to first understand what kinds of immune cells cause T1D in patients who take ICPIs and then test out the possibility of using JAKis to reverse the disease. The approach not only prevented T1D, but in some cases even reversed it.
“We are really excited about the potential of these medicines to be used in cancer immunotherapy-induced autoimmune diseases, because it’s a much faster path to the clinic,” Dr. Lechner said. She noted that the approach could also be used to address more frequent side effects of ICPIs as well — an important need as immunotherapy becomes a more common approach to treating cancer.
Dr. Lechner and her team are now in talks with the NIH to lead a clinical trial out of UCLA to test the approach in the real world.
"The DoM’s continued strong support of early-career physician scientists makes UCLA a great place for our team to execute these bench-to-bedside studies and address the clinical challenges faced by our patients in the laboratory,” she added.
Congratulations to Dr. Lechner and her team on their outstanding work!
Yusuke Tsugawa, MD, MPH, PhD Leads Study on GLP-1RAs and Dementia Risk
I am delighted to share an important study and highly visible study, led by Yusuke Tsugawa, MD, MPH, PhD, a health services researcher and associate professor of medicine in the general internal medicine and health services research division. Dr. Tsugawa’s team recently reported in Annals of Internal Medicine that despite some excitement about the potential of GLP-1 receptor agonists (GLP-1RAs) to prevent dementia in patients with type 2 diabetes (T2D), they were unable to find strong evidence of this in individuals over the age of 75.
“The findings were much more modest than previous studies that claimed up to 60% reductions in dementia risk,” Dr. Tsugawa said. “The lack of clear overall benefit contradicted some previous observational studies with methodological limitations.”
To conduct their research, Dr. Tsugawa’s team used a method called “target trial emulation,” an approach where scientists use real-world Medicare data to create a “virtual” clinical trial. Their study included data from 14,295 adults aged 66 or older who took the medication metformin alongside either a GLP-1RA or a dipeptidyl peptidase-4 inhibitor (DPP4i), an older drug also used to treat T2D.
If GLP-1RAs are protective against dementia, there would be a lower incidence of the condition among those who took them compared to DPP4is. The researchers were careful to match patients using statistical techniques to make sure the groups were as similar as possible and followed them for a median of 1.9 years. They tracked when dementia symptoms likely began as well, which was defined as 1 year prior to official diagnosis.
When they analyzed the data, Dr. Tsugawa’s group found no clear overall difference in dementia risk between the two medication groups. Around 4% of patients who took GLP-1RAs developed dementia, compared to a rate of 4.5% among those who took DPP4is. Unexpectedly, GLP-1RAs seemed to be mildly protective in slightly younger patients, but the effect was not statistically significant.
“First, there is no clear evidence that GLP-1RAs reduce dementia incidence compared to DPP4is overall in older adults with diabetes,” Dr. Tsugawa concluded. “Second, age matters significantly, as any potential protective effects may be limited to adults younger than 75. Third, more rigorous research is needed, specifically randomized controlled trials with longer follow-up periods are essential for definitive answers.”
Dr. Yusuke noted that the study has some limitations, such as a relatively short follow-up time, potential unmeasured confounding factors and a possible underdiagnosis of dementia. Additionally, the biological mechanisms by which GLP-1RAs might affect dementia may differ by dementia type, with patients with vascular dementia versus Alzheimer’s disease potentially responding differently. Future research will require longer follow-up periods, and studies in patients without diabetes are also needed.
“Given the growing burden of dementia and widespread use of these medications, these findings have important implications for treatment guidelines and patient counseling,” Dr. Tsugawa said.
Congratulations to Dr. Tsugawa and his team! I appreciate the acknowledgement that the present work makes a strong case for longer-term studies to address this important issue. I look forward to seeing the impact of this research in this rapidly evolving field.
UCLA Endocrinology Shares Research and LEADERShip at Endocrine Society Conference
The UCLA Division of Endocrinology had a great turnout at the Endocrine Society’s annual meeting on July 12 through 15 in San Francisco. Our faculty and fellows shared their research, learned from others and networked with physicians and physician-scientists who may one day become their collaborators.
“The Endocrine Society has always been one of my favorite conferences,” Angela M. Leung, MD, MSC, an endocrinologist at the VA and UCLA who has been attending the conference since 2005 and presented several sessions. Dr. Leung was also recently appointed to serve as a member of the Board of Directors of the Endocrine Society. “The programming always features the most cutting-edge and impactful research, and it's a great meeting to see the field positively impacted by science, education and advocacy.”
Five of our eleven endocrine fellows attended the meeting. Robin Hilder, MBChB, MSC, a STAR fellow based at Olive View-UCLA Medical Center, was selected for participation in the prestigious Endocrine Fellows Conference: Type 1 Diabetes Care and Management. Elyssa Berg, MD, Alexandra Lim, MD, Diana Torres Pinzon, MD, MPH and Katayoun Khoshbin, MD presented posters on recent challenging clinical cases.
“Attending the Endocrine Society conference as a fellow was an enriching and impactful professional experience,” said Dr. Khoshbin, who presented two separate posters at the meeting. “It allowed me to engage directly with leading endocrinologists, build valuable connections and gain exposure to cutting-edge research and clinical advancements.”
Among our faculty, Dr. Leung was highly involved in this year’s conference, presented a session to dispelling myths on the use of diet to control thyroid disease as well as two separate talks. Her session, “Diets for the Thyroid: Fact or Fiction,” was one of the selected highlights for the Endocrine Society’s Endocrine Mentor Day, where local medical students and residents join the meeting as guests for a day. Her two talks were part of the Endocrine Educator Forum’s Endocrine Pipeline series, which highlighted the diverse interest of trainees pursuing an endocrinology career and Endocrine Society initiatives to support the next generation of endocrinologists. Additionally, Dr. Leung moderated the gestational thyroid symposium, which summarized the latest updates in thyroid disease during preconception, pregnancy and the postpartum period.
Another one of our faculty LEADERS who played an active role in the conference was endocrinologist and health services researcher Estelle M. Everett, MD, who serves as co-chair — and future chair — of the Endocrine Society’s CODI committee, that is charged with ensuring that the Society’s programs and activities are inclusive and promote the career advancement of all its members irrespective of background. In addition to presenting her own research on diabetes technology use, she was also involved in planning several events at the conference, including the Health Disparities Symposium, Health Disparities Poster Preview, LGTQIA+ Reception and the Mentoring Poster Reception. For Dr. Everett, CODI’s event to mark the group’s 30th anniversary was one of the most meaningful points of the conference.
“Hearing from past leaders reminded me that the work we do through CODI is part of a larger legacy and that we have a responsibility to continue evolving to meet the needs of our current and future members,” Dr. Everett said. “It was inspiring, energizing, and affirmed why this work matters so deeply.” As future chair of CODI, she spoke about the group’s vision moving forward.
“This event underscored the Endocrine Society’s longstanding and ongoing commitment to creating a professional community where all members feel supported and valued,” she said.
Dr. Everett collaborated with Matthew J. Freeby, MD, director of the Gonda Diabetes Center and the associate director of diabetes clinical programs at the David Geffen UCLA School of Medicine, on the study she presented at the meeting. For Dr. Freeby, the conference offered a chance to spend time with old friends and colleagues and to consider further opportunities for research.
“The involvement of UCLA faculty and fellows was impressive and evident by the number of clinical and research presentations, showing the large footprint our institution has at the Endocrine Society meeting,” he said.
I attended the meeting as well. During CODI’s anniversary celebration, I gave a presentation on the committee’s many accomplishments over the past three decades. It was exciting to watch our new fellows take part in such an important event, and I was proud to see our faculty and trainees held in high esteem among their peers! Here is a complete list of the abstracts presented by our fellows and their mentors:
- Dr. Berg with mentor Megan M. McConnell, MD: Tumor-Induced Osteomalacia Secondary to Orbital Mesenchymal Tumor with Excessive Production of Fibroblast Growth Factor 23 Dr. Elyssa Berg and Dr. Megan McConnell
- Dr. Robin Hilder with mentor Jane Weinreb, MD: Therapeutic Challenges in Post-Transplant Renal Osteodystrophy
- Dr. Khoshbin with mentors Amit K. Sumal, MD and Sheila Ahmadi, MD: A case of PTH dependent and independent hypercalcemia -
- Dr. Khoshbin with mentors Kyrstin L. Lane, MD and Sarah S. Kim, MD: An unusual presentation of histoplasmosis: bilateral adrenal masses and hypercalcemia
Enjoy photos from the conference below!
Dale
P.S.
My travel challenge last week generated a large and interesting response.
For some it triggered the poem by mother goose:
"There was an old woman who lived in a shoe."
“There was an old woman who lived in a shoe.
She had so many children, she didn't know what to do.
She gave them some broth without any bread;
And whipped them all soundly and put them to bed”.
Dr. Judy Currier noted: “ Sure looks like Storyland in North Conway NH to me. Jesse grew up there ( Madison) his great Aunt was in fact the lady in the shoe.”
Dr. Jeff Borenstin noted: “While I have no idea where this is located, I did find it interesting how many shoe-shaped houses there are”, and shared a remarkable link from a google search “House in the shape of a big shoe."
However, there were three correct answers, that were provided by:
Dr. Rajat Singh – Division of Gastroenterology: “the Shoe House is located in a park somewhere in Bombay/Mumbai, India! 🙂”
Dr. Estelle Everett – Division of Endocrinology: “"Mumbai, India! I'm not sure how many of these exist around the world, but this definitely looks like the Shoe House I visited during a trip for an Endocrine Society talk a few years ago."
Dr. Hrish Kulkarni -Division of Pulmonary Critical Care and Sleep Medicine. “The shoe in your newsletter is from Mumbai (I think), where I grew up. I remember going there as a child, so it immediately rang a bell.”
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