Year 3. September 3. Celebrating our Leadership in Cardiovascular Medicine.
Two months ago, we welcomed our new Chief of Cardiology, Dr. Priscilla Hsue. This week, in addition to an extended introduction and welcome for Dr. Hsue, I wanted to focus on some of the many areas of cardiovascular research excellence within the UCLA Cardiology Division and UCLA Department of Medicine (DoM), which exemplifies the foundation on which Dr. Hsue will build.
Ashley F. Stein-Merlob, MD, PhD, is Awarded a KL2 Career Development Grant
Join me in congratulating the UCLA Division of Cardiology’s Ashley F. Stein-Merlob, MD, PhD on receiving a KL2 grant! She will receive $130,000 per year for the next three years to continue building a modeling framework to understand cardiac amyloidosis. This project will be conducted under the mentorship of Alan Garfinkel, PhD and Lihua Jin, PhD.
There was a time when cardiac amyloidosis — a condition where deposits of abnormally misfolded protein structures, or fibrils, build up in the heart — was thought to be a very rare genetic disease. Yet a growing body of evidence suggests that not only are the genes linked to it more common than previously thought, but that the incidence increases with age regardless of genetic susceptibility.
With few good animal models to turn to, Dr. Stein-Merlob dedicated her time in graduate school to developing a mathematical model that simulates the mechanism behind the disease and the effects of different treatments. Now, with her KL2 grant, she will expand her model into three dimensions and replicate the patterns by which misfolded protein fibrils build up in the heart’s walls. Her model will also show how the fibrils impact the shape and mechanics of the left ventricle.
Dr. Stein-Merlob’s project will ultimately inform precision medicine approaches to treat cardiac amyloidosis. The first drug approved to treat the disease, tafamidis, is around $194,000 per year after discounts. That high cost makes it imperative to figure out who is the right candidate and the optimal time in their disease course to initiate this drug and others that are coming down the pipeline. Robust models of the disease will be instrumental for making those decisions.
Dr. Stein-Merlob views her research and practice of medicine as deeply intertwined. As a physician-scientist, she has the resources she needs to answer the many questions that arise from her work with patients — a pursuit helped along by her engineering background, which affords a unique perspective on clinical mysteries and helps her build what she needs to solve them.
“For me, being a physician-scientist is really perfect, because I get to integrate both my love of caring for patients and my desire to ask and answer questions,” Dr. Stein-Merlob said.
Learn more about Dr. Stein-Merlob's research in the video below!
Learn More About Recent Studies by our Research Superstars in Cardiology
We “❤️” our research LEADERS in the UCLA Division of Cardiology! Take a beat to check out their exceptional work from the past few months.
Karol E. Watson, MD, PhD Co-edits Circulation’s Heart Disease Disparities Research Issue
For the past four years, the journal Circulation has dedicated an annual issue to research on disparities in heart disease incidence, care, and outcomes linked to race and other sociodemographic characteristics. Karol E. Watson, MD, PhD, attending cardiologist and professor of medicine/cardiology at UCLA, has served as co-editor of this important edition since its inception. Among the articles accepted for this year’s issue, which published last month, she noticed a compelling trend: a shift toward solutions.
“As the disparities issues have gone along, the difference I’ve seen is that we’re really trying to get toward solutions and not just documenting the problems,” Dr. Watson said. “All of these solutions will be very, very difficult — we get that. Some of the innovative strategies that people look towards are the really interesting things that we see in this issue especially.”
Among those solutions are the use of artificial intelligence to put a new lens on old databases and comb through them with finer tools, a strategy that Dr. Watson predicts will have a major impact on the field in the future. But low-tech ideas, like planting trees, could be impactful too: One study found that people living in neighborhoods with greenery had lower rates of subclinical atherosclerosis than residents in more barren areas.
Disparities research is some of the most challenging to do because many things that clearly contribute to outcomes, like the experience of racism, are difficult to capture quantitatively, Dr. Watson explained. Of all the types of research she’s conducted — from basic science to epidemiology — disparities studies were the most challenging.
“The fact that we are getting so many high-quality submissions shows that it really is maturing as a field, and the response to our issues has been phenomenal,” she said. “This is really good science, and I love that disparities research is entering that era."
Beyond co-editing the disparities issue, Dr. Watson is also an associate editor for Circulation, one of the top cardiovascular journals in the world. Though the role is “a lot of work,” as she puts it, she views it as part of the greater mission of creating and spreading new knowledge.
“If we don’t take leadership roles, then a lot of the most important research access and influence is lost,” Dr. Watson said. “Being involved is absolutely transformative and fundamental."
Tomohiro Yokota, PhD Identifies Potential Treatment for Diastolic Heart Failure
There are few effective therapies for heart failure with preserved ejection fraction, also known as diastolic heart failure or HFpEF, even though it’s found in roughly half of all heart failure patients. Now, Assistant Professor-In-Residence Tomohiro Yokota, PhD and a team of researchers within and outside of UCLA, have uncovered a mechanism that causes HFpEF to form, identified how it’s distinct from another common form of heart failure, and shown that using a novel drug in the class of glucagon receptor antagonist appears to be effective against the condition in two preclinical animal models. The results of this collaborative project, largely conducted at UCLA, were published this month in an article in Circulation Research.
“We have not only identified a critical molecular signaling pathway that differentiates HFpEF and heart failure with reduced ejection fraction, but also proved that targeted manipulation of the glucagon signaling pathway can be used as a therapeutic strategy for disease management,” Dr. Yokota said. He noted that the study raises important questions about glucagon signaling in the heart and what other types of cells might be involved, such as immune cells and fibroblasts, and that future studies to answer them could offer collaboration opportunities for the UCLA cardiovascular community and beyond.
“Ultimately, the combined expertise from basic biologists and clinicians would help our discoveries translate from the bench to the bedside,” Dr. Yokota said.
Marmar Vaseghi, MD, PhD Finds Mechanism Behind Anesthesia’s Rhythm-regulating Effects
Next is the work of Marmar Vaseghi, MD, PhD, professor of medicine and cardiology in the section of electrophysiology. After small case series showed that a type of anesthesia called thoracic epidural anesthesia (TEA) can prevent a dangerous abnormal heart rhythm called ventricular arrhythmia in patients with heart failure who don’t respond to other types of treatments, Dr. Vaseghi’s lab set out to understand the mechanism behind these effects. In a paper published June 28 in the journal Circulation Research, her team showed that the approach reduces dangerous heart rhythms and stabilizes the heart electrically in two ways: by reducing electrical abnormalities due to the sympathetic nervous system and by improving vagus nerve responses, also known as improving vagal tone.
“We know that dangerous rhythms are associated with sympathetic nervous system activation and vagal dysfunction, so people have postulated and performed studies that suggest interventions that improve vagal tone, like vagal nerve stimulation or even meditation, could also reduce the burden of arrhythmias,” Dr. Vaseghi explained. “We were interested in seeing whether TEA could stabilize the heart electrically by not only blocking sympathetic neural traffic from the spinal cord to the heart at a particular point of the neuroaxis, but could also improve vagal tone by blocking the sympathetic signaling from heart to the brain that may be causing vagal dysfunction, providing an additional anti-arrhythmic effect.”
The findings suggest that it may be possible to take a targeted approach to using neuromodulation to reduce ventricular arrhythmia in heart failure patients, perhaps by blocking just the signaling between the heart and the brainstem to improve vagal tone. Such an intervention could not only offer an important treatment option for patients with hard-to-treat abnormal heart rhythms, but also could potentially reduce the dose or eliminate the need for the multitude of medications currently required to manage their heart disease.
Jesús A. Araujo, MD, MSc, PhD Studies the Link Between Heart, Gut and Air Pollution Impacts
We now turn to the latest findings from the UCLA Division of Cardiology’s Jesús Araujo, MD, MSc, PhD, who worked alongside Jonathan Jacobs, MD, PhD and his team in the UCLA Division of Digestive Diseases to investigate the potential effects of air pollution on acute colitis. In their July 2024 article in the International Journal of Molecular Science, they described how they found that while air pollution molecules are toxic to a line of intestinal cells called Caco-2 cells, they don’t seem to exacerbate disease severity in two different animal models of colitis— at least not at the particle levels and exposure duration used in the study.
Dr. Araujo is actively investigating the mechanisms by which air pollution exposure raises traditional cardiovascular risk factors such as blood levels of lipids like cholesterol and triglycerides, including the possibility that these changes are mediated by pollution’s effects on gut bacteria and lipid metabolism. The results of the new study are another step towards untangling a complex web of interactions that could eventually help us understand how pollution affects the heart and determine who might be most vulnerable. Other recent interdisciplinary work by Dr. Araujo’s team has demonstrated in mouse models that inhaled ultrafine particles alter the gut microbiome and that diesel exhaust dysregulates immune cells called macrophages.
We mentioned in our August 19th newsletter that Jason Hong, MD, PhD had a forthcoming study in Circulation on the mechanisms of pulmonary arterial hypertension. That research has now been published and can be found here.
Boback Ziaeian, MD, PhD, Leads AHA/ACC Performance Measures Updates for Heart Failure
The influence of DoM faculty extends far past the walls of the UCLA Health system into clinics and labs around the world. One shining example of this is the leadership of Boback Ziaeian, MD, PhD, assistant professor of medicine in the UCLA Division of Cardiology, in the development and publication of the 2024 Update to the 2020 American College of Cardiology/American Heart Association Clinical Performance and Quality Measures for Adults for Heart Failure.
Dr. Ziaeian is the chair elect of the 2024 ACA/AHA Committee for Performance Measurement and a member of the writing committee. As chair elect, he is involved in leadership decisions about the creation, maintenance and progress of all performance measure committees and in advocating for their use in quality-of-care assessments by major payers, such as the Centers of Medicare and Medicaid Services. As a member of the writing committee, he and others were responsible for reviewing current heart failure guidelines and rewriting performance measures.
Dr. Ziaeian’s work with the ACA/AHA performance measurement guidelines has informed the development of his research, which focuses on improving access to evidence-based care in cardiology health services. He believes he has also benefitted from having the opportunity to assess evidence objectively alongside other experts and is grateful to be involved in an effort that shapes the practice of medicine.
“We help move the needle forward how care quality should be monitored and perhaps reimbursed,” Dr. Ziaeian said. “As we develop better payment models that are not only based on fee for service, quality of care should be rewarded as well.”
Stephen Young, MD Named a 2024 American Heart Association Distinguished Scientist
Join me in congratulating Stephen Young, MD, distinguished professor of medicine and human genetics at UCLA, was one of seven people to be named a 2024 Distinguished Scientist by the American Heart Association (AHA). The honor, one of the highest given by the AHA, is reserved for scientists whose work has significantly advanced our understanding of cardiovascular diseases and has been given to only 151 researchers since 2003.
“I am very grateful for this recognition and for decades of research support from the American Heart Association,” Dr. Young said.
Dr. Young’s many contributions to science include the investigation of the genetic and molecular physiology of the protein apolipoprotein B, the movement of fatty acids into tissues and the role of nuclear lamins in health and disease. He discovered the first genetic mutations that lead to low plasma cholesterol levels, also known as familial hypobetalipoproteinemia. He and his UCLA colleagues Loren Fong, PhD and Anne Beigneux, PhD discovered that a protein called GPIHBP1 is crucial to the breakdown of fats called triglycerides, and that its absence can result in high triglycerides in the blood. They also found that mutations in the gene GPIHBP1 cause lifelong high triglycerides, and that the body can form antibodies to GPIHB1 later in life and lead to the same effects. Dr. Young, Dr. Fong and Dr. Beigneux discovered that this “GPIHBP1 autoantibody syndrome” can be treated with drugs that suppress the immune system, a finding that has saved lives.
Dr. Young’s team is also behind the discovery that the combination of high triglycerides and low levels of the protein APOA5 is caused by low levels of the enzyme lipoprotein lipase (LPL) inside blood capillaries. They also found an explanation for the low LPL levels in these patients. Specifically, APOA5 prevents an LPL inhibitor from removing LPL from the surface of capillaries.
Dr. Young is also a member of the National Academy of Sciences, the American Society for Clinical Investigation and the Association of American Physicians. Please join us in celebrating his recognition by the AHA!
I hope you will agree that our faculty in the UCLA Division of Cardiology are would leaders in the field of cardiovascular medicine and cardiovascular research. Your work keeps UCLA at the cutting edge of innovation that moves medicine forward!
Let me now shine the spotlight on Dr. Priscilla Hsue, who joined the DoM as Chief of Cardiology.
In Conversation with…Chief of the Division of Cardiology Priscilla Hsue, MD
In July the department welcomed Priscilla Hsue, MD as our new chief of the UCLA Division of Cardiology. She is a pioneer in the field of HIV cardiology whose passion and curiosity have illuminated a path of groundbreaking discoveries that continue to transform patient care.
Dr. Hsue’s interest in medicine was sparked in the sands of her hometown of Los Alamos, New Mexico, where she grew up surrounded by science. Like many others in her community, both of her parents were nuclear physicists. It was clear early on that she shared their love of learning — and wanted to combine science with helping others.
A career in medicine was in her sights from the start, but the deal was sealed during college. At the time, news was breaking of a mysterious illness that would eventually become known as HIV. She knew instinctually that medicine, and HIV in particular, was the right application for her passion for science and people.
While Dr. Hsue was accepted to several MD-PhD programs on the East Coast, she was sure her destiny was westward. She opted to forgo the formal physician-scientist track to attend medical school in at UCSF instead, and today believes this experience serves as an example to those at the start of their own careers that there is more than one way to fulfill a dream.
Once she arrived in California, the seeds of her rise to the top of her field as both a leader and a researcher began to take root. While working in a safety net hospital as a medical student, she had an experience that she credits with informing her approach to leadership: A combative patient who was hospitalized for uncontrolled HIV and withdrawal from intravenous drugs lunged at her with a needle when she tried to draw his blood.
After stepping out of the room to collect herself, she realized she would need to establish a rapport with him. She returned to the room and listened to him, trying to understand his perspective despite their very different backgrounds. In the end, she was able to draw his blood — and to this day, she believes that this ability to establish a relationship and connect with individuals, gained in those harrowing moments, have been instrumental to her success as a leader.
What experience shaped your leadership approach?
Meanwhile, her career at the intersection of research and medicine began to take shape and evolve. Though an interest in virology brought her out west, her experience as a physician sparked curiosity about cardiology — fields that seemed too disparate to build a career at their intersection. Then, in the clinic, they collided: While still a trainee, Dr. Hsue noticed relatively high rates of heart attacks among persons with HIV. This observation led to the discovery that chronic inflammation caused by the virus makes it an independent risk factor for heart disease and led to a focus on inflammation as a means to reduce cardiovascular disease as well as impact HIV cure.
This breakthrough, and the many others that followed, taught Dr. Hsue the value in being someone who “swims outside her lane.” She is often the only cardiologist at meetings for other fields, but showing up creates an opportunity to connect dots that galvanize innovation. As such, her studies of inflammation in HIV-associated cardiovascular disease help to inform a broader understanding of the role of inflammation and immunology in the heart, hopefully leading to novel therapeutic strategies that can help all individuals.
How does looking outside your field lead to scientific breakthroughs?
Indeed, interdisciplinary collaborations are leading to what Dr. Hsue and other cardiologists describe as a “renaissance” in the field. For example, drugs that are reshaping the landscape of obesity treatment have the potential to do the same for cardiometabolic disease, and gene therapies that have so far been reserved for devastating genetic conditions are making their way into cardiology.
This new era brings many more opportunities for UCLA Cardiology to reinforce its status as a leader in the field. Dr. Hsue wants to build upon the division’s strong basic science foundation to expand translational and clinical research. For instance, she is very excited about the California Institute for Immunology and Immunotherapy; in particular building upon her studies in HIV, and feels this is a tremendous opportunity to study the role of the immune system in cardiovascular disease.
Dr. Hsue’s vision also includes capitalizing on her admittedly competitive streak to establish the division as the nation’s top cardiology program across the board, from research to patient care, and to see its prominence reflected in higher U.S. News and World Report rankings. That means more NIH grants, more clinical trials and more junior investigators — and, importantly, even more educational and research opportunities for students, cardiology fellows and early-career faculty.
What’s your vision for the future of cardiology at UCLA?
No matter the obstacle, Dr. Hsue’s passion for medicine motivates her to persist despite it. That drive is at the heart of her advice to early career physicians and junior investigators: If you love what you do, you’ll make it through. She also encourages those who are just starting out to take smart risks and go where the challenges are. As someone who has built a career out of connecting the dots between disciplines in ways that might have seemed precarious to some, Dr. Hsue has learned that whether making career moves or asking research questions, being fearless pays off.
What advice do you have for early-career physician-scientists?
We recently hosted a welcome event for Priscilla. I invite you to view the highlights in this video!
Dale,
P.S.
Last week we highlighted some canine stars within the DoM. The video went viral, so much so that many of our faculty and trainees pointed out to me that we did not include perhaps the most famous dog in the DoM, Zoe.
So, Zoe, here's to you!
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