Blazing new trails

At  3 a.m. on an October Saturday in 2017, Chaz Langelier was wide awake and unloading climbing gear from his Toyota Prius in California’s Sequoia National Park after driving through the night from San Francisco. There was no time for sleep as Langelier and his climbing partner set off on a 17-mile trek into the wilderness where they would establish two new 1,000-foot routes on remote granite domes. Then, on Sunday evening, less than 48 hours after beginning the adventure, Langelier would drop his partner off in a small city outside the park and head home. At the time a junior faculty member at the University of California, San Francisco, he needed to be back and on point for a presentation Monday morning. 

Six years later, Langelier (pronounced “lon-JEL-yay”) hasn’t slowed his pace. Now an associate professor of medicine at UCSF and a Chan Zuckerberg Biohub Investigator in San Francisco, Langelier has co-authored over 100 studies in the fields of infectious diseases and critical care medicine while providing care for patients — all while continuing to establish new climbing routes in some of the least traveled regions of California’s High Sierra. He is leading a pioneering UCSF initiative, with support from CZ Biohub SF, to track infection outbreaks in hospitals using genomic sequencing technology. Beyond that, his lab is developing new methods for diagnosing and managing infectious diseases by using cutting-edge sequencing technology to simultaneously profile patient immune responses and detect microbial pathogens.  

And though a passion for extreme outdoor sports may seem worlds apart from a passion for medicine, Langelier’s colleagues say the audacious spirit Langelier displays in the mountains carries over to his work as a scientist and physician.

“What’s rare about Chaz is that he qualifies in the elite category of athletes, but he’s also an amazing clinician–scientist who’s way above average in terms of the number of publications he puts out,” says Joe DeRisi, CZ Biohub SF president and Langelier’s academic advisor during his medical residency at UCSF. “His ability to take strategic, calculated risks keeps him alive in the mountains, but it also means he’ll try all kinds of stuff in the lab that ultimately advances his research, and makes him a better clinician as well.” 

A childhood on the slopes

Langelier’s love of the mountains was instilled early during a childhood in Vermont near the Quebec border where “skiing was just something that you did.” A cross country ski racer both in high school and during his undergraduate studies in biochemistry at Colby College in Maine, Langelier always made sure outdoor adventure wasn’t too far off when choosing new steps in his professional career. After college, an M.D.-Ph.D. program at the University of Utah allowed him to balance an intense academic path with world class climbing, skiing, and mountain biking in the Wasatch mountains. These days, he frequently makes quick trips to Yosemite National Park, even if only for 24 hours.

Langelier on the summit ridge of Mt. Gardiner, in California’s Kings Canyon National Park. (Credit: Vitaliy Musiyenko)

At work, Langelier talks little about his alter-ego as a wilderness trailblazer, his colleagues say. But for anyone who has known him long enough, the clues start to stack up. 

“Sometimes Chaz would come back to the lab completely beaten up at the end of a weekend, with giant cuts on his legs and arms,” says DeRisi, who remembers one instance during Langelier’s early days at UCSF when he refused to seek care for a “festering” hand wound until he finished an important experiment. “When he was finally done in the lab, we made him go to the Emergency Department.” 

Natasha Spottiswoode, a resident physician at UCSF who chose Langelier as her mentor during her research residency, spoke with Langelier about outdoor adventuring before she came to UCSF. A skilled skier and climber herself, Spottiswoode was eager to hear about access to the climbing and skiing spots around San Francisco. But Langelier was humble about his exploits, and it took some time for her to fully understand the extent of his climbing resume. She was “surprised and amused” to discover that many friends who were serious climbers (but with no connection to medicine) already knew who Langelier was.

Having worked closely with Langelier for many years, DeRisi and Spottiswoode now know that their colleague once ran 100 miles across a mountain range in Utah, that an ice climbing route he helped establish in 2007 made the cover of Climbing Magazine two years later, and that numerous routes to his credit appear in a premier guidebook of climbing in the High Sierra. 

Despite these feats, however, Langelier himself contends that he’s “nowhere near the level of a professional climber” and that he “really just enjoy[s] the unsurpassed emotional and physical experiences that climbing brings.” And while few would doubt he could have been a professional adventurer had he chosen that path, it’s clear to those who know him that Langelier’s devotion as a professional will always be to science and medicine. 

From mountains to medicine

It was a wholly different kind of adventure, in fact, that cemented Langelier’s passion for infectious disease research and treatment. Early in his M.D.-Ph.D. training, Langelier was studying the biological mechanisms through which HIV infects human cells. One summer he traveled to a small town in Uganda to volunteer in a medical clinic for people living with HIV/AIDS, which debilitates patients’ immune systems, sometimes leaving them at serious risk from what are typically mild infections. 

The Ugandan clinic struggled with a lack of resources at a time when antiretroviral drugs for HIV were not widely available in the region. Without those medications, which can keep HIV at bay by stopping viral replication, doctors and nurses were instead left trying to save patients from a continuous onslaught of opportunistic infections taking advantage of their weakened immune systems.

Unfortunately, their efforts were often stymied by a lack of diagnostic tests that could allow them to identify the actual microbes causing a patient’s infection. Helping patients in that clinic in Uganda, Langelier developed a deep drive to help find better ways to approach infectious disease diagnosis and treatment. “I was so deeply impacted by the experiences of the people I met, and it really made me realize how many key questions there are about infectious diseases that are just not answered,” he says.  

Langelier in his lab. (Credit: Susan Merrell/UCSF)

Langelier ultimately realized that even in the best resourced parts of the world, common infectious disease syndromes like sepsis and pneumonia lack accurate diagnostics, and thus are often treated blindly without doctors ever identifying what virus or bacterium is causing the problem. That means patients might receive treatments that are ineffective, or more often they may receive unnecessary or inappropriate antibiotics, a problem that is driving increased drug resistance in deadly microbes. With this in mind, Langelier pivoted his research to focus on pathogen discovery, inspired by DeRisi’s pioneering work using metagenomic next-generation sequencing (mNGS) to detect both known and novel pathogens causing infectious diseases, like meningitis, sepsis, and pneumonia. In 2014 he joined DeRisi’s lab at UCSF determined to learn to apply this technology to saving lives and advancing our understanding of infectious diseases.

A new view of diagnostics

Since then, Langelier has built much of his career around mNGS, with promising results. Last year, for example, Langelier and colleagues, including Katrina Kalantar, lead computational biologist at the Chan Zuckerberg Initiative, reported that they had combined mNGS with machine learning to create a paradigm-shifting approach for diagnosing sepsis, an out-of-control immune response to infection that is linked to millions of deaths worldwide each year. This tool combined analyses of genetic material from pathogens with measures of how patients’ bodies ramp up and tamp down the expression of certain genes in response to specific invaders — a combination that increased the predictive power of the approach.

Langelier crack climbing in Kings Canyon National Park in California. (Credit: Vitaliy Musiyenko)

Related work by Langelier and colleagues has pioneered new approaches to improving the diagnosis of lower respiratory tract infections, the causes of which often go undetected. And his lab has shown how this technique can be used to detect pathogen drug resistance and be translated into a rapid diagnostic test designed to detect any SARS-CoV-2 variant. Through ongoing international collaborations, Langelier is also helping to understand the causes of respiratory infections and sepsis in rural settings in Africa, where a lack of locally obtained data has forced physicians to rely on that collected in other parts of the world when trying to develop clinical treatment guidelines. And most recently, he led a study on the immune system response to SARS-CoV-2, shedding light on why older adults are at higher risk of severe Covid-19.

In the U.S., tens of thousands of patients die each year because of infections they contract while receiving medical care, and the nation’s healthcare system spends billions of dollars working to prevent such infections from spreading. With support from CZ Biohub SF and the Department of Hospital Epidemiology and Infection Prevention at UCSF, Langelier has helped implement mNGS to address infection outbreaks at the UCSF’s hospitals. This initiative is allowing medical professionals to identify outbreaks much faster and giving them the tools to detect pathogens they may never have encountered before. Langelier hopes that the program — one of the first of its kind — will eventually become the norm in hospital systems everywhere, helping to solve the age-old problem of hospital-acquired infections. 

“There’s some sort of intellectual courage that drives Chaz to look at a medical problem and say, ‘It really doesn’t have to be this way,’” says Spottiswoode. “And maybe it’s the same kind of intellectual bullheadedness that leads someone to look at an unexplored mountain face and say, ‘I bet we could go up there.’”