Year 4. April 21. Breadth of Our Community Impact
It is a privilege to lead such an amazing team of colleagues. In times of crisis, I have directly observed how we have rallied around each other and, when necessary, set aside our vested interests to ensure that others are not left behind. This week, I chose to reflect on stories about some of our colleagues in the UCLA Department of Medicine (DoM) who are making an impact locally and around the world, starting with work that has arisen out of the recent wildfire tragedy and extending across the globe to support our partners in Malawi.
UCLA Health Wildfire Steering Committee to Lead Research on Fire Health Impacts
Climate change is very much in the news and could contribute to some of the natural disasters that challenge many communities, including our own. The recent wildfires put into sharp focus the impact of environmental catastrophes on our personal sense of safety and wellbeing. Many of our colleagues in the DoM are still recovering from the devastating wildfires that destroyed so much of Pacific Palisades and Altadena just a few months ago. These and future fires will undoubtedly have an impact on public health, and research into the magnitude of their effects is essential for preparation and mitigation efforts.
To that end, the UCLA Center for Translational and Clinical Science Institute (CTSI), the David Geffen School of Medicine at UCLA (DGSOM) and the UCLA Fielding School of Public Health recently formed the UCLA Health Wildfire Steering Committee, a multidisciplinary group of researchers who will set the institution’s priorities for wildfire research. Several DoM faculty were selected to be members of the committee, which is chaired by David Eisenman, MD, a professor in the division of general internal medicine and acclaimed disaster researcher.
“We’ve got one of the largest populations in America that was exposed to a huge environmental hazard,” Dr. Eisenman said. “The wildfires will have very clear health effects on L.A. residents — we had smoke all over the county for several days with very high concentrations of toxins, metals, volatile compounds and ash. We know from the literature that’s dangerous to people’s heart and lung health, but we don’t know the full extent of its effects.”
The Wildfire Steering Committee’s goals are to serve the L.A. community, to build and maintain its trust and to conduct comprehensive, long-term health impact assessments over a wide swath of the L.A. County population. They will collaborate with other programs across UCLA as well as other academic medical centers in the region, including USC and Cedars-Sinai.
“Everyone’s making sure to maintain connections and inform each institution about what they want to do and find ways to collaborate,” Dr. Eisenman said.
The committee’s first priorities will be to clarify the fires’ health impacts by establishing the UCLA Health Wildfire Research Fund, the UCLA Health Wildfire Prioritization Committee and the UCLA Health Wildfire Registry. The research fund will provide monetary support for rapid pilot grant submissions through the UCLA Clinical & Translational Science Institute; the prioritization committee will oversee the selection of studies that involve UCLA Health patients, resources and research infrastructure. The wildfire registry is a registry of subjects who are open to participating in studies on the fires’ effects, along with potentially providing biological samples for a biobank.
“This centralized registry approach will mitigate impacted people from being individually approached to participate in multiple studies while concurrently, encouraging excellent research that serves a public health purpose, is comprehensive, and includes those exposed and willing to participate,” Chief Medical Officer for Clinical Research for UCLA Health and CTSI Co-Director and DoM faculty member, Arash Naeim, MD, PhD a geriatrician, oncologist, and wildfire committee member, said.
Evan M. Shannon, MD, an internist and clinical investigator in the UCLA Division of General Internal Medicine and Health Services Research and hospitalist at the West Los Angeles VA, joined the Wildfire Steering Committee because he wanted to ensure that health equity is a priority when it comes to deciding what research projects are funded. He is particularly interested in understanding how climate change will impact homelessness; as a committee member, he will be able to advocate for programs and research activities that include unhoused people.
“Often when there are large scale disasters, the communities that are already the most vulnerable are impacted the most,” Dr. Shannon said. “UCLA Health has a responsibility to ensure that the firestorm doesn’t widen health disparities that are already present across the county.”
More information on the application process for rapid pilot funding will be shared soon. Thank you to all of those who applied to be part of this initiative. There will be more opportunities for faculty to engage in UCLA’s response to the wildfires in the coming months. The department continues to work closely with our affected faculty and provide mental health, emotional support and material help to those who need it.
Jesus Araujo, MD, MSc, PhD Takes Creative Approach to Air Pollution Research Translation
While there is little question that pollution impacts human health, it is no simple task to tease apart the mechanisms behind its myriad effects on the body. One of our all-star researchers doing just that is Jesus Araujo, MD, MSc, PhD a cardiologist who studies how particulate matter in the ambient air, diesel exhaust and other forms of air pollution lead to atherosclerosis and heart disease.
“We have been very interested in looking at the translation of the findings obtained in our experiments with animals and how these inform the effects we see in humans,” Dr. Araujo said. “We have seen a good degree of correspondence between both.”
When Dr. Araujo started his lab more than 20 years ago, the conventional thinking in environmental medicine was that air pollution affected human health mostly through the lungs. His team was among the first to find experimental evidence to understand why people who died from air pollution did so because of heart attacks or strokes.
"Our initial interest was to determine whether those epidemiological associations represented a real possibility that one could lead to the other,” he said. “We embarked on animal studies where we set up mouse models of exposure to the air pollution to study cardiovascular effects"
That research showed that exposure to ultrafine particles (UFPs) and fine particles (FPs) found in air pollution could causally lead to atherosclerosis in mice. Dr. Araujo’s team also identified biomarkers associated with UFP and diesel exhaust exposure, a key step towards translating their animal research to humans. To go further, his team set up a study involving UCLA students who traveled to Beijing — a city with even more air pollution than L.A. Their work showed that the biomarkers linked to air pollution in mice were also elevated in humans, even after just six to eight weeks of exposure (and while most of them declined to prior levels after seven weeks back in the U.S., some of them did not).
Importantly, the pollution levels in Beijing were high enough that the subjects were exposed to UFP and FP levels on par with those of the animals in the Araujo lab’s experiments, or even more. That gives the experimental design more validity with regards to applying findings from mouse studies to humans.
“We realized that there was very good translation of these things that had been detected in the mice, and into the effects the particles could be having,” Dr. Araujo said. His team has continued to expand upon those findings, including in a study published in late December that showed a wide range of genetic and metabolic effects induced by air pollution in mice. Those results offer a mechanistic explanation for observed epidemiological links between type 2 diabetes, fatty liver disease and diesel exhaust exposure, as well as a potential therapeutic targets.
In addition to studying air pollution, Dr. Araujo’s lab is also investigating the cardiovascular effects of electronic cigarette (e-cigarette) and hookah smoke. A study published by his team in early February showed that e-cigarette fumes cause cardiac rhythm and heart rate variability in mice, findings that built upon earlier research indicating the presence of similar biomarkers associated with e-cigarette smoke in humans. That suggests that those biomarkers observed in humans could be harbingers of downstream cardiovascular effects. Notably, some of the biomarkers are the very same ones that rise after air pollution exposure.
“It was sort of a reverse engineered process from the one we used to study air pollution. For air pollution, we started with animals to see if the effects we saw could be translated in humans, while in the case of e-cigarettes, we started with the effects in humans and turned to the animals to try to understand them better,” Dr. Araujo explained.
Translational research is difficult for many reasons, not the least of which being that it is far easier to control experimental conditions for animal studies than it is for those involving people. Creativity and flexible thinking are essential to its success.
“There are challenges in being able to establish translatability between the mouse studies and the human studies, but it’s incredibly important,” Dr. Araujo said. “In humans, the importance of animal studies is that they allow us to understand what is occurring with the human physiology. If we don’t have that, the animal studies lose their relevance.”
As wildfires and other natural disasters caused by climate change become more common, the urgency to translate environmental biomedical research between animals and humans will only rise. Dr. Araujo’s lab is working on ways to figure out who is most susceptible to the effects of air pollution and the mechanisms by which they are affected — work that could ultimately lead to targeted therapies.
“In the case of wildfires, you could have an intervention that may decrease the susceptibility of the people who are at risk, or even block the effects altogether,” Dr. Araujo said. “That’s what’s driving our interest as we continue our work in this area — we want to get to the actual mechanisms that allow us to develop therapeutic strategies that can prevent the effects induced by these environmental factors.”
Barbara Natterson-Horowitz, MD, PhD Collaborates with Nature to Move Medicine Forward
This week’s focus coincides with Earth Day. As such, I would like to recognize the work of one of our DoM LEADERS whose research at the intersection of human health and wildlife biology has sparked a new field of medicine. Barbara Natterson-Horowitz, MD, PhD is a cardiologist and author who has built a prolific career seeking insights into human health from the millions of animals that live alongside us on planet Earth.
“Across the animal kingdom there are species that share vulnerability to many of the most challenging biomedical threats to our species,” said Dr. Natterson-Horowitz, who also serves as the co-director of the UCLA Evolutionary Biology Program. “ The health vulnerabilities we share with other species — from breast cancer and endometriosis to atrial fibrillation and cardiomyopathy — are an overlooked source of insights for physicians.”
Dr. Natterson-Horowitz's species-spanning approach to biomedical research began in the mid-2000s when she became cardiovascular consultant to the LA Zoo. Among the research initiatives she has led since that time is a study of cardiovascular adaptations of modern giraffe species, which she proposed might be a natural animal model of resistance to heart failure with preserved ejection fraction.
Giraffes have the highest blood pressure of any animal on Earth; their normal systolic blood pressure approaches 300mmHg, a consequence of the nearly three vertical meters the left ventricle must pump blood to the brain. The giraffe ventricle is thick to accommodate this pressure, yet they do not develop the fibrosis and stiffness characteristic of humans with hypertrophic ventricles. Critically, their exercise capacity remains excellent — they flee predators at 30 to 40 kilometers per hour.
"My original hypothesis was that ancestors of modern giraffe had evolved some kind of fibrosis suppression physiology allowing for thick ventricles without compromised hemodynamic function strategy,” Dr. Natterson-Horowitz explained. She organized a consortium of physiologists, veterinarians and cardiologists from around the world and put together a project to test this hypothesis. The outcome was important insights not only into both human and giraffe cardiovascular health.
That work was the basis for later discoveries by researchers from China of an anti-fibrosis gene found in giraffes that protects them from fibrosis in their hearts. When that gene was transplanted using CRISPR into mice, they did not develop fibrosis as readily as mice that did not receive the gene. While those findings have not yet been translated into a clinical product, the findings “have sharpened my focus on the use of gene editing to bring evolved adaptations conferring resistance to a range of pathologies to human patients,” Dr. Natterson-Horowitz said.
Since then, Dr. Natterson-Horowitz's research has led to discoveries of animal evolutionary adaptations relevant to sudden cardiac death, psychiatric conditions, infertility, and more. She is currently collaborating with UCLA pulmonologist and critical care physician Emily R. Schwitzer, MD to learn whether rodents that live near volcanic mountains have developed evolutionary mechanisms to protect their lungs from smoke and ash. They have found morphological and anatomical evidence in lung structures called cilia that suggests this is indeed the case. That could have implications for improving human health because the ash from volcanoes is similar to particulate matter from wildfires and urban air pollution.
"Biodiversity can be a source of novel strategies; natural selection can be seen as a process that leads to the most effective, innovative solutions. There may be evolved adaptations that have salience for many high-impact human medical challenges.” Dr. Natterson-Horowitz said. For example, with UCLA cardiology fellow Karam Gill, MD, she is studying electrogenic fish to identify adaptations that may protect them from ventricular arrhythmias.
In addition to her research with Dr. Schwitzer, Dr. Natterson-Horowitz is also working on a project that assesses whether there are some types of animals that are relatively resistant to a deadly cardiac arrhythmia called ventricular fibrillation. To find out, she is working with a group of evolutionary biologists and electrophysiologists to study creatures that live in close proximity to electrogenic fish, which hunt using electricity.
“My hypothesis is that animals that are surviving around electrogenic fish possibly have evolved fibrillatory thresholds that are higher than fish that don’t have to deal with that electric environment,” Dr. Natterson-Horowitz said. She believes that the findings from this work could ultimately lead to better pacemakers and other anti-arrhythmia therapies — and that her cross-species approach to biomedical research will grow in popularity as data from initiatives like the Earth BioGenome Project become more complete.
"In recent years interest in understanding the connections between human and animal health has grown rapidly among physicians and medical students.” she said. “I am heartened by this because we become better doctors when we recognize that we share vulnerability to disease with multitudes of other species. We become better investigators when we recognize biodiversity as a source of biomedical innovation — and we become better humans when we recognize our responsibility to protect not only human lives, but the health and well-being of all life on Earth.”
Partners In Hope Changes Lives of Patients — and the Physicians Who Learn From Them
Earth Day reminds us that we all call the same planet home, whether we are in Los Angeles or on the other side of the world in Malawi, an East African nation where the UCLA Global Health Program collaborates with a non-profit called Partners In Hope. Partners In Hope’s longstanding collaboration with DGSOM and the DoM has taught countless students and trainees how to manage care for low-resourced patients with HIV, tropical infectious diseases and chronic health issues. Many of them credit it with shaping their careers; that includes Faysal Saab, MD, an internist and pediatrician who first took part in our Malawi rotation in 2012 when he was a fourth-year medical student.
“I have a lot of gratitude towards that opportunity, because it set me off on a path to really start refining and honing my clinical skills in the absence of fancy, expensive tests that more of our world is relying on to diagnose conditions,” he said. "It was important for me to have a more well-rounded understanding of medicine and include that in my education, and the global health program allowed me to do that.”
Dr. Saab was so moved by the experience that he joined the UCLA Global Health Pathway during residency and even became faculty in the program as a chief resident. Today, he serves as the pathway’s associate director; he lived in Malawi prior to the COVID-19 pandemic and continues to take part in rotations at Partners In Hope’s facilities, where he works closely with the medical staff and supervises UCLA medical students and residents.
“We're going there to ask questions and be dry sponges that soak in what we can from those who have been practicing there for much, much longer,” Dr. Saab said. “There’s this misconception in global health that we’re going there as saviors. No — we go with a 'learners first' mentality, because I could list off plenty of things they do better in healthcare in Malawi than they do in the United States.”
One of the biggest lessons is in how to do more with less. Diagnostic tools that we take for granted in the U.S., like CT and MRI machines, are not widely available at hospitals in Malawi. Healthcare practitioners must instead rely on their refined history and physical exam skills to make diagnoses and decide what treatments to give.
“I think that our current U.S. healthcare system has such a heavy reliance on advanced imaging modalities and laboratory tests that trainees here often use them as a replacement for strengthening that clinical muscle and trusting their training. They may turn to diagnostic imaging because it’s so easy, and we just want to be 100% sure,” Dr. Saab said. “I think there's so much importance to have that as a reminder of how to practice when there isn't much available, and for me to teach that mentality to medical students and residents.”
Partners In Hope’s facilities are a lifeline for many patients across Malawi, especially for people living with HIV. Yet the non-profit's operations were recently threatened by cuts to USAID — a U.S. government agency that provided funds to many health-focused organizations around the world — and a pause on foreign aid provided under PEPFAR, a Bush-era program that supported HIV care initiatives across the globe. This endangered Partners In Hope’s ability to get medications to those who need them and would have affected the lives not only of current patients but generations to come.
Those developments prompted the Global Health Pathway leadership to galvanize support for Partners In Hope by encouraging donations to African Mission Healthcare, a 501(c)(3) nonprofit that was created by a longtime Partners In Hope collaborator. Fortunately, the U.S. State Department recently “rescinded” the termination of a grant that supports Partners in Hope’s work.
"This is great news, but there will be a significant investment required to rehire and ramp up activities again,” Daniel Kahn, MD, associate director of the Global Health Pathway, said. “Thankfully, with the success of our emergency fundraiser, patients at PIH have not had a significant gap in their access to life-saving car.”
Thank you to Dr. Kahn, Dr. Saab and all of those involved with Partners In Hope and the Global Health Pathway for your commitment to promoting health around the world.
Liza Buchbinder, MD, PhD Studies Environmental Medicine in Eastern Togo
Let me highlight the work of a DoM member who is bringing together anthropology and medicine to advance health for all. Liza Buchbinder, MD, PhD is a hospitalist, jail physician, author and medical anthropologist who has dedicated much of her career to studying the health impacts of human trafficking and environmental degradation in a village in Togo, a country in West Africa. She recently served as editor on a special edition of Culture, Medicine, and Psychiatry in which physicians and social scientists used the practice of cultural ethnography — a research method used to understand cultures and communities — to reflect on the challenges of their clinical work and document how our field has changed since COVID-19.
“I hope that this special issue sheds light on the importance of speaking out and advocating for patients, families and healthcare workers on how an ethnographic approach can provide out-of-the-box insights and understandings about the practice of medicine,” Dr. Buchbinder said.
Dr. Buchbinder is using cultural ethnography in her own work on a UCLA Global Health and DoM-funded study that investigates how deforestation has impacted the residents of a Togo village where she once conducted research on human trafficking for her PhD.
“I returned to update my data for my first book on human trafficking, and I was just devastated by what I saw in the community — all of the trees had been cut down in the 10-year period of time from when I had done my doctoral research to the time I came back,” she said.
The project investigates how deforestation affects the use of indigenous medicines and healing practices among people in the community, who have a spiritual relationship with the trees. As science often does, her research so far has revealed one problem nestled within another: While the villagers are indeed impacted by the loss of the teak trees that they would use to create medicines, more imperative is a lack of consistent access to Western drugs that they also use for ailments.
“When I asked about the trees, the villagers told me, ‘This is the least of our problems. We need a nurse who will stay in the village for more than six months and a stocked pharmacy for when we have a crisis or people have infections,’” she said. “They need antibiotics, clean water, things like that — the trees really are of lower priority.”
Dr. Buchbinder will return to Togo this summer to conduct the second stage of her study on deforestation. She views cultural ethnography as an important tool for physicians to make sense of a complex world, no matter where they are.
“As a practice of self-reflection that is both immersive and shaped by clinical experiences, ethnography offers tools for documenting how structural forces and power inequities impact sickness and health,” Dr. Buchbinder said.
Let me close by thanking our exceptional colleagues, including many not mentioned in this piece, for your commitment to our local and global communities and to the health of our planet.
Dale
P.S.
Last week I had the opportunity to meet with many of our physician scientist residents, to talk about various things, including their concerns about support for research at this critical stage of their career. I encouraged them to stay the course and reminded them that the DoM has their back.
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