Faculty Spotlight: Eveline Stock, MD

From the age of four, Dr. Eveline Oestreicher Stock knew she wanted to be a doctor. Born in Chuquicamata, a copper mining town in northern Chile, she often accompanied her mother on her hospital visits as part of the Damas de Rojo (Ladies in Red), a volunteer organization which brings material and spiritual support to patients.

She also went with her mother to Chilean highland villages in the middle of the Atacama Desert to help pregnant women who had limited access to medical care. “We visited tiny little towns with llama farmers, brought them clothes and food, and made sure women could reach a medical facility to deliver their babies,” said Dr. Stock. “We always wanted to help people – that was our thing.”

When she was seven, her father, a mining engineer, took a one-year contract in San Francisco, and brought the entire family. “It was a big culture shock,” said Dr. Stock. “Imagine coming from this little mining town, where for fun on the weekends we would go to the nearest town to watch the only traffic light. It was a huge change coming to San Francisco, but the experience opened up a whole new world, one that made me think I could make a difference, and that anything was possible – even building 50-story buildings in earthquake-prone areas!”

Dr. Stock earned her medical degree from Pontificia Universidad Católica de Chile in Santiago, Chile, where she also completed her internal medicine residency, chief residency and endocrinology and metabolism fellowship. Her exacting professors emphasized the importance of doing a thorough physical exam, and she practiced listening to the heart by going to sleep with her stethoscope on her chest. “I would breathe in and out, and listened to how the sounds changed,” she said. “I was obsessed with understanding the underlying secrets leading to disease.”

She was initially interested in becoming a surgeon, because she thought that would be the most direct way to help patients. “Then I realized that people were often getting sick because of preventable diseases, and that sparked my interest,” said Dr. Stock. She was drawn to endocrinology – the study of hormones – because of the fascinating and complex nature of endocrine disorders. “You can really dive deep into the molecular level and get an understanding of the interrelationships between the different organ systems and cells,” she said. “That was very appealing to me.”

Dr. Stock also became interested in the role that hormones play in contributing to high blood pressure, which in turn caused injury to blood vessels in the heart. She met Harvard endocrinologist Dr. Gordon Williams at a scientific meeting, and ended up training with him at Harvard Medical School and Brigham and Women’s Hospital in Boston, completing an endocrine hypertension research fellowship. She then decided to stay in the U.S. to pursue her career, which required her to repeat her internal medicine residency in this country – which she did, at Massachusetts General Hospital.

Her fellowship research on how hormone imbalances could contribute to high blood pressure and heart disease sparked her interest in cardiology. “It was a natural leap to go into cardiovascular diseases, because I wanted to apply my knowledge to help prevent disease and have an impact on people’s lives,” said Dr. Stock. She came to UCSF for her cardiology fellowship, and joined the faculty in 2014.

Her own experience of re-doing internal medicine residency and jumping through bureaucratic hoops to obtain a visa and other permits inspired her to reach out to others. “I want to bring attention to people who are in minority groups or who are not recognized as people of excellence, but who truly are in their own right,” said Dr. Stock. She has served as a diversity mentor and has worked to recruit diverse resident applicants both at Harvard and UCSF.

“I encourage them to apply for scholarships and academic positions, and to get them to realize that it is possible to have access,” she said. “UCSF is very inclusive, and it’s one of the reasons I enjoy working here. It recruits the best minds, regardless of your origin. It is also a place that’s very open to new ideas, and has excellent mentoring.”

Lipid Detective

Dr. Stock divides her time between clinical work and research. As a clinician, she works in the UCSF Center for Prevention of Heart and Vascular Disease, where she sees general cardiology patients. She also works in the echocardiography lab, where she interprets ultrasounds of the heart, helps oversee the stress test lab, and conducts transesophageal echocardiograms – in which an ultrasound probe is inserted down the esophagus to provide high-quality images of the heart.

In addition, she serves as an attending physician in the UCSF Lipid Clinic. Dr. Stock and her colleagues identify and manage lipid conditions, including cholesterol and triglyceride disorders and other diseases which can contribute to heart disease or stroke if left untreated. They employ a wide range of tools, including a thorough physical exam, obtaining a detailed patient history, and conducting molecular and genetic analyses. The clinic has reported five previously unknown lipid diseases, which have had unexpected implications for other conditions as disparate as diabetes, Parkinson’s disease and Alzheimer’s disease.

“I feel like I have to help every patient who comes into my care,” said Dr. Stock. “Even if I don’t know what exactly is wrong with them, I want to alleviate their anxiety or suffering. If I can help them further by finding out what the underlying cause is, that’s a huge drive for me.”

Dr. Stock takes unsolved questions into the laboratory, where she works with endocrinologist Dr. John Kane on uncovering the root causes of lipid disorders. One of her primary areas of interest is high-density lipoprotein (HDL), sometimes known as the “good” cholesterol, which helps to remove other forms of cholesterol from arterial walls.

“People think that cholesterol is inherently bad, but it’s actually not ‘good’ or ‘bad,’” said Dr. Stock. “It’s a molecule that combines with proteins called lipoproteins – such as HDL and LDL – which are carried in the bloodstream. Their effect on health depends on many factors.”

Dr. Kane’s lab is a world leader in illuminating the hidden world of HDL, which they are discovering may play a critical role in a wide array of areas, including vascular disease, immunity, fertility and neurological diseases. HDL appears to be involved in transporting signaling molecules, which are an essential element of how cells talk to each other.

Dr. Kane’s lab also discovered a new way to isolate HDL molecules from plasma samples: rather than using a centrifuge, which spins samples at up to 80,000 revolutions per minute and can damage and distort HDL in the process, his lab uses a gentler process to separate HDL so it can be accurately studied. Thanks to this innovation, their group has discovered that there are about 20 subspecies of HDL – and that each type contains different proteins and has different functions.

For example, Dr. Stock is collaborating with postdoctoral scholar Dr. Kate Creasy on a pilot study of patients who have had heart attacks, yet had no known risk factors. “One of my big interests is understanding this population, who come to us in their 30s, 40s or 50s after they’ve had a heart attack, but they have no clue why,” said Dr. Stock. “They exercise, eat well and don’t smoke.” She and Dr. Creasy found differences in HDL-related signaling proteins called cytokines in such patients compared to similar study participants who had not had heart attacks.

In addition to two known heart disease risk factors – elevated levels of low-density lipoproteins (LDL), which are sometimes known as “bad” cholesterol, and inflammation of the arteries – Dr. Stock is working with other members of Dr. Kane’s lab to examine a novel third element involved in the development of atherosclerosis: the ability of the artery to get rid of excess cholesterol. They have identified a subspecies of HDL called prebeta-1 HDL, which appears to accept excess cholesterol from the artery wall and carries that cholesterol to the liver, where it is excreted from the body. “This third element appears to be key in maintaining vascular health, a novel risk factor,” she said.

Dr. Stock has analyzed prebeta-1 HDL levels in more than 2,300 individuals. Interestingly, she and her colleagues found that unusually high levels of prebeta-1 HDL actually correlates with a high risk of coronary artery disease. Dr. Kane likened prebeta-1 HDL to a garbage truck coming down the street to pick up cholesterol. “If the cholesterol can’t get out of the cell, more and more trucks accumulate, and that’s why you have a high level of prebeta-1 HDL,” he said. “So those people build up levels of this molecule waiting for the cholesterol.”

Their group is especially excited that prebeta-1 HDL can be measured through a simple blood test, so this novel method of measuring heart disease risk could potentially be administered widely one day, similar to the way HDL and LDL levels are currently measured.

“Eveline is really special in a lot of ways,” said Dr. Kane. “She has her certification as a cardiologist, but she’s also had deep background in endocrinology and lipid metabolism. There aren’t many people who have that combination – I could probably count them on my fingers in the United States. The depth of what she offers is not available in most divisions of cardiology. It gives her insights that people in cardiology wouldn’t naturally have, because she’s thinking about the molecules. She even tells me that she goes to bed at night thinking about these molecules!”

Transforming Lives

In addition to laboratory research, Dr. Stock helps conduct clinical trials of potential therapies for patients with lipid disorders. “Now with technology, we can synthesize enzymes that are lacking in people,” she said. For example, a rare disease called lysosomal acid lipase deficiency develops when lysosomes – the waste disposal system of a cell – lacks an enzyme which allow the liver to break down excess cholesterol. Without this critical enzyme, patients develop fatty livers, which can lead to cirrhosis. In its most severe form, the condition is called Wolman’s disease, and babies who have it usually die before their first birthday.

Using recombinant enzyme technology, the missing enzyme can be grown in the egg whites of chickens. In a clinical trial, all three patients treated with the synthesized enzyme experienced improvement. “Their livers reduced in size, their lipids improved, and now they’re virtually disease-free,” said Dr. Stock. “They just need to keep getting this enzyme every month. One of the patients told me that before, she didn’t make plans because she didn’t think she had a future. This therapy changes people’s lives.”

Another disorder that Dr. Stock has worked on is called familial chylomicronemia, a rare genetic disorder which causes patients to develop abnormally high triglyceride levels, which can then cause pancreatitis – a painful inflammation of the pancreas. Scientists have developed an RNA-antisense molecule that can block the production of a particular enzyme associated with the disease right at its origin, and Dr. Oestreicher and her colleagues are now testing the effectiveness of this therapy.

“It’s very satisfying, because you see patients normalize their [triglyceride] levels,” she said. “These are patients with few other options for treatment. We’ll see if these drugs get approved down the road. But we’re entering a new era of drug development where we’re targeting things very specifically and not using the shotgun approach.”

When she’s not in the lab or the clinic, Dr. Stock enjoys hiking, sailing in San Francisco Bay, cooking, and spending time with her husband and their two young children.