Academic Spotlight: Ashley Cristal, MD

Ashley Cristal
Ashley Cristal, MD

Bringing Bedside Manners to the Lab

As a college student at New York University, Ashley Cristal, MD, volunteered to organize art projects and parties for hospitalized children. “That cemented my decision to go to med school, and I wanted to become a pediatrician,” he said.

As a medical student at the University of Santo Tomas in the Philippines, Dr. Cristal found himself drawn to many different areas of medicine, including internal medicine, radiology, ophthalmology, and in particular, neurology. “I think for most medical students, there is a process of discovering what one is interested in and enjoys doing, as well as the realities of each specialty,” he said. In his case, he found that in addition to caring for patients, he was drawn to the rigor of academic medicine as well as teaching patients and helping them become more engaged in their health care.

After graduating from medical school, he returned to the U.S. and chose to explore career avenues in clinical research. He was accepted as a postdoctoral research associate at Yale School of Medicine in the lab of neurologist Elan Louis, MD, MS, helping discover more about movement disorders.

“I really fell in love with clinical research,” said Dr. Cristal, who now works as a specialist in the lab of Jeffrey Olgin, MD, chief of the UCSF Division of Cardiology and Gallo-Chatterjee Distinguished Professor of Medicine. “I taught patients about their condition – how it might have developed, their risk factors, how to take their medication, and things to look out for. Participants who enroll in studies are often curious and ask a lot of questions. I really enjoy their inquisitiveness and helping them become more informed…. There’s something for everyone in medicine, and I found my niche in clinical research, where I still get to work on the front lines with participants. And what our team finds out might someday help millions of health care professionals around the world prevent and treat heart disease in patients.”

On the Road for Research

As a postdoc in Dr. Louis’s lab at Yale, Dr. Cristal coordinated nationwide studies on the genetics of essential tremor (ET), the most common movement disorder, and the role of environmental biomarkers on the development of Parkinson’s disease and ET, which in some cases may have a hereditary component. He and his team of other postdocs and research assistants fanned out around the country, collecting data from study participants and their families. They made clinic and home visits in big cities, rural communities, farms, and as far away as Alaska and Hawaii. They administered questionnaires, conducted blood draws and cognitive assessments, and videotaped participants so neurologists could assess tremor severity.

Their research helped shed light on baseline knowledge about ET among patients and their families. Self-reportedly “unaffected” first-degree relatives of ET patients often have mild, subclinical tremor; their investigations suggest that close relatives of ET patients have a higher likelihood of mild cognitive deficits and transient, isolated head tremor, and are more likely to reduce their consumption of caffeine, a substance which can exacerbate tremor.

Over his three years as a postdoc, Dr. Cristal estimates he collected data from about 160 participants during visits lasting between three and eight hours. “The diversity across this country is amazing,” he said. “I met people of varying social demographics and politics. They were so accommodating and hospitable. Some liked to tell stories. Others said, ‘Just stay for lunch!’ It was fun to see the country and go places I never thought I’d go.”

Traveling solo required problem-solving skills and teamwork. One of the biggest challenges was finding dry ice to preserve biomarker samples. “Before going out, I tried to find all the dry ice vendors,” said Dr. Cristal. “Sometimes I’d have to drive 100 miles to get it and 100 miles back. A dry ice box can last 48 hours before we have to ship it to our collaborators. It’s like getting an extra life in a video game – ‘I’ve got this much time. Then I have to refill.’” He also relied on his team, asking colleagues in the office to ship new supplies to his hotel. “We all worked together and supported each other,” he said.

As the team supervisor, Dr. Cristal trained his members to collect field data in standardized ways. “We did a lot of repetition to make sure everyone was on the same page,” he said. “I had them shadow each other and give feedback. Are we recording the video correctly? How are we doing with our blood draws? Are we getting the quantity of blood we need?” He started them on local visits in Connecticut or New York before sending them further afield.

Digital Clinical Research: Collecting Data at Scale

When his postdoctoral fellowship ended in 2018, Dr. Cristal came to UCSF to work with Dr. Olgin’s lab as a clinical research coordinator, and was promoted to specialist in 2021. “Dr. Olgin does a lot of work in digital clinical research, which attracted me,” he said. “I like finding ways to use technology to conduct clinical research, find new methods to diagnose and treat disease, and make people more proactive in their health care.” He was especially impressed that Dr. Olgin and his colleagues had already received support from the National Institutes of Health to create the Eureka digital research platform. This tool makes it easy for academic, nonprofit and industry researchers to securely conduct research using mobile apps, sensors, and connected devices.

He sees digital clinical research as a way to broaden access, helping people participate even if they work full-time, live far away, or face mobility or transportation challenges, among other obstacles. “When the pandemic happened, everyone realized, ‘We need to get on the digital train and make our studies more flexible,’” said Dr. Cristal. For example, one study he had been working on had two cohorts – one composed of UCSF patients who were recruited and set up with study devices in-person, and another completely remote cohort made up of participants from across the U.S., identified from the Health eHeart Study, who had their devices mailed to them. “When COVID hit, we dropped the in-person study requirements and went fully remote, since we were already set up to do so,” he said. “It was fortuitous that we were already in a position to be flexible enough so we could become purely remote.”

Dr. Cristal has worked on the Health eHeart Study, a longitudinal cohort study that uses digital surveys, smartwatches, fitness trackers, and other technologies to improve understanding of cardiovascular disease. He currently focuses much of his time on the Biomarkers of Early Atrial Transformation in Atrial Fibrillation Study (BEAT-AFib), another longitudinal study which is investigating biomarkers for atrial fibrillation, the most common heart arrhythmia. Those could include markers in the blood, changes in imaging such as echocardiograms, MRIs or EKG tracings, or survey responses. “We want to find possible risk factors for otherwise healthy people who develop AFib,” he said. “What biomarkers change when they actually develop AFib, and what treatments could help prevent this?”

He points to the success with atherosclerosis, in which researchers learned more about lipid profiles and high-density lipoproteins (HDL) and low-density lipoproteins (LDL) as biomarkers of the disease, then developed statins and other treatments in response. “We’re trying to find something similar for AFib,” said Dr. Cristal. “When we find a biomarker that helps us understand more of the pathophysiology and etiology of AFib, that could help us tailor a treatment or procedure to help prevent and treat it. It could also help us develop new guidelines to reduce risk by avoiding potential triggers, and to recommend dietary and lifestyle changes.”

Participants periodically answer surveys on their smartphone or online, use smartwatches and reusable patches to collect EKGs, automatically contribute sleep and physical activity data using their smartphone, and come in annually for the first several years to contribute blood samples and get an echocardiogram and high-resolution EKG.

“By having participants do most activities at home and just come in once a year for other tests, it allows us to collect a lot more data and handle larger cohorts,” said Dr. Cristal. “In many traditional studies, participants come to clinic for the research, go home, and that’s it until their next in-person visit, if there are any. For an episodic disease like AFib, it can be very difficult to capture the needed information during a single visit. By providing tools to our participants, we can empower them to collect data between these visits, almost in real time. That’s where digital clinical research really shows its value…. These studies are really important for the future of health care and clinical research, and are the most cost-effective, efficient way of collecting huge amounts of data.”

A Teacher at Heart

Of course, digital clinical research comes with distinct challenges. These include educating participants, many of whom are older or less tech-savvy, how to use apps, wearable devices, and other new tools. Dr. Cristal applies his medical background and love of patient education to answer questions and help participants successfully contribute data. “We’re always looking for ways to make things easier for participants,” he said.

For example, they developed instruction manuals and a list of frequently asked questions to help participants set up devices and troubleshoot problems. They created videos demonstrating how to apply a wearable EKG patch and use the app to start recording heart rhythms. “A study like this collects real-time data that participants can see,” said Dr. Cristal. “Seeing the faces of my participants light up who had never used any of these devices before reminds me of why I fell in love with clinical research. It also feels like you’re giving people hope that something may be just around the corner that might help them or their families.”

He enjoys mentoring his team, and shares approaches he developed during medical training. Dr. Cristal emphasizes the importance of demonstrating good bedside manners, whether a research participant comes in for a site visit or calls with questions. “Study participants always come first,” he said. “They are the most important person in the room, on the telephone, or on email. Don’t ever talk down to them, but also be mindful of their education level, and tailor how you explain things based on how much they know. Remember that participants aren’t just data points or subjects – they’re human beings, just like us.”

He encourages research coordinators to educate themselves so they can answer participant questions. “Read the protocol, then read it again,” said Dr. Cristal. “Learn more about the different diseases and why we’re doing various tests for this study, because participants will ask you and might get frustrated if you can’t fully explain things to them. One of the greatest resources of UCSF is all the brilliant minds who work here. Dr. Olgin gives quick presentations about topics like why we’re doing echocardiograms, and every other PI and attending has always been happy to answer questions from staff.”

Dr. Cristal goes out of his way to build rapport with participants, making small talk and asking about their day. “That’s one of the easiest ways to motivate people,” he said. “The more comfortable they are with you, the longer they’ll stay in the study, and the happier they’ll be. It’s also the best way to collect quality data. We want to get people excited to contribute and make it as easy as possible for them to do so.”

He coaches his team on helping participants relax during their 15-minute high-resolution EKG. Because any muscle tension in the body can create electrical signals which interfere with the heart recording, it’s important for them to stay as still as possible. “I tell them, ‘Let’s do some breathing exercises,’” said Dr. Cristal. “‘We really want you to take a deep breath – exhale. Take a second deep breath – exhale. Tense up your shoulders as tight as you can. Then just relax your shoulders completely. Remember that feeling of getting all that tension and stress out of your shoulders. I want you to close your eyes and go to your happy place, whether that’s in the mountains, on the beach, or on vacation with family, friends and good food.’”

Dr. Cristal also works closely with EKG Core Lab Manager Valerie Carp, who reviews each recording and gives suggestions on how to improve. “That’s what’s cool about our team – everybody is happy to cross-train each other and give feedback,” he said.

“Ashley brings a rare mix of experience which includes conducting research and leading teams, as well as medical knowledge that helps the team ground the daily work in why the research is important,” said Dr. Olgin. “All this is coupled with a calm, nurturing and ‘let’s get it done’ leadership style.”

‘Every Day I Learn Something New’

Dr. Cristal grew up in Toms River, N.J., where his father was an internist in private practice. He graduated with a bachelor’s degree in politics from New York University and worked as a medical assistant in his father’s office. He completed his medical degree from the University of Santo Tomas in Manila, Philippines, where some of his extended family members had also graduated from medical school. “It was an opportunity not only to achieve my goal of becoming a physician, but also to reconnect with my family and heritage,” he said.

Today, given his own less-traveled road through medicine, Dr. Cristal appreciates mentoring non-traditional students as they pursue STEM careers, as well as foreign medical school graduates as they prepare to match into residency or explore careers in clinical research.

He also values the close-knit nature of the Olgin Lab and the entire Division of Cardiology, especially during the stress of the pandemic. Dr. Cristal developed COVID in March 2020 after visiting family in New York and was bedridden for a month, including more than a week in the hospital. “Everyone supported me through that whole period, asking if they could deliver anything to my house and checking in nearly daily,” he said.

Outside the lab, Dr. Cristal is an avid landscape photographer, plays guitar, loves baseball and trivia, and runs 20 to 30 miles each week, including the equivalent of a half-marathon every weekend.

He is very happy to be working at UCSF. “The resources, people, faculty and staff are awesome,” said Dr. Cristal. “This is one of the best institutions in the world. Everyone is at the top of their game. I love doing clinical research here, and every day I learn something new.”

-Elizabeth Chur