Year 4. April 21.
[Dr. Abel Intro]
UCLA Health Wildfire Steering Committee to Lead Research on Fire Health Impacts
The impact of climate change is already quite visceral here in Los Angeles, where many of us — including our colleagues in the DoM — are still reeling 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 the health of our communities, and research into the magnitude of their effects is essential for preparation and mitigation efforts.
To that end, UCLA Center for Translational and Clinical Science Institute (CTSI), the David Geffen School of Medicine at UCLA and the UCLA Fielding School of Public Health have formed the UCLA Health Wildfire Steering Committee, a multidisciplinary group of researchers who will set the institution’s priorities for wildfire research. Several faculty from the UCLA Department of Medicine were selected to be members of the committee, which is chaired by professor, internist and disaster researcher David Eisenman, MD.
“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 look out for,” 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 Office of the Vice Chancellor for Research & Creative Activities; 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 biological samples in a biobank.
“This centralized registry approach will help protect impacted people from being sought out by researchers for different studies, and at the same time, encouraging excellent research, serving a public health purpose, being comprehensive, and including those exposed and willing to participate,” CTSI Co-Director Arash Naeim, MD, PhD, a gerontologist, hematologist 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 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 and material support to those who need it.
Dr. Araujo 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 all-star UCLA researcher who is doing just that is Jesus Araujo, MD, PhD, MSc, a cardiologist who studies how particulate matter in 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 our findings obtained in our experiments in 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 through the lungs. His team was among the first to find epidemiological evidence that people who died from air pollution did so because of heart attacks or strokes.
“Our initial interest was to determine whether these associations represented a real possibility that one could lead to the other,” he said. “So we embarked on animal studies where we set up and models of exposure to the to the air pollution and to study cardiovascular effects.”
That research showed that exposure to ultrafine particles (UFPs) and fine particles (FPs) found in air pollution could lead to atherosclerosis in mice. Dr. Araujo’s team also identified biomarkers associated with UFP and FP 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 are also elevated in humans, even after just ten 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 early December that showed a wide range of genetic and metabolic effects from 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 target.
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 build upon earlier research indicating the presence of biomarkers associated with e-cigarette smoke in humans. That suggests that those biomarkers observed in humans could be harbingers of downstream cardiovascular effects. Notably, the biomarkers are the very same ones raised following 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 human 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 Collaborates with Nature to Move Medicine Forward
As we continue our Earth Day celebration, I would like to recognize the work of a DoM LEADER whose research at the intersection of human health and wildlife biology has sparked a new field of medicine. Barbara Natterson-Horowitz, MD 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 Earth.
“These animals share vulnerabilities to many of the same diseases that are very difficult to deal with among people, from cancer and congenital defects to trauma,” said Dr. Natterson-Horowitz, who also serves as the co-director of the UCLA Evolutionary Biology Program. “Animals are vulnerable to cancer. Animals are vulnerable to congenital abnormalities and pregnancy difficulties. But as physicians, we don’t typically think about human health as connected to the health of other species.”
Dr. Natterson-Horowitz's species-spanning approach to biomedical research began in the early 2000s, when she began noticing an increasing number of women coming into her practice with a form of heart failure that was associated with hypertension. She wondered if there were animals that had evolved adaptations to protect them from heart failure due to high blood pressure.
As it turns out, there are: As those of you who went through medical school may know, the giraffe has the highest blood pressure of any animal on Earth because blood must travel a long distance from its heart to its brain. Yet giraffes do not develop heart failure and even run quickly for long distances to flee predators — something a human with the same blood pressure would not be able to do, as their blood pressure would lead to fibrosis, thickened ventricles and eventually heart failure.
“My hypothesis was that they had evolved some kind of fibrosis suppression strategy,” Dr. Natterson-Horowitz explained. “I put together a project with a very interesting group of scientists and physicians, and we tested the hypothesis in a number of ways.”
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. 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 “really opened my eyes to this possibility,” Dr. Natterson-Horowitz said.
Since then, Dr. Natterson-Horowitz's research has led to discoveries of animal evolutionary adaptions 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.
“This is really exciting to think about. If we really look at biodiversity as a source of solutions, are there other species that have evolved adaptations that have salience for high-impact human medical challenges?” Dr. Natterson-Horowitz said. “It's not the way that biomedical research has traditionally approached these issues, but it can."
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.
“I'm very heartened by what I see is powerful shift towards connecting human health to animal health,” she said. “I think that there are going to be major human health challenges, both physical health and mental health, that are transformed by opening our eyes to the natural world and recognizing the deep connection between human and animal health.”
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 observes 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 learner’s first mentality, because I could list off plenty of things they do better 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 consistently present as a reminder for me as a faculty member 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 in the communities that surround them, especially for people with HIV. Yet the non-profit's operations are threatened by the recent 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. These developments dramatically undermine Partners In Hope’s ability to get medications to those who needed, affecting the lives not only of current patients but generations to come.
“The number of babies who will contract HIV because they are born to mothers with HIV who are no longer on medication and the number of patients who will have untreated, drug-resistant tuberculosis is going to spread not just in Malawi, but all over the continent and all over the world,” Dr. Saab said. “The funding cuts are absolutely devastating. I cannot understate this.”
The DoM is committed to continuing to fund our operations in Partners In Hope for as long as possible. To augment our financial support, the UCLA Global Health Program has recently launched a fundraiser TKTKTKTK.
Liza Buchbinder, MD, PhD Studies Environmental Medicine in Eastern Togo
To cap off our Earth Day celebration, I will now highlight the work of a DoM faculty 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 in 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.
Dale
P.S.
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