Personalized Journey Booklet

Brian,

Brian,

What drives your passion for medicine? For me, it began with a deeply personal journey. Growing up in the LA area, my family’s healthcare experiences as immigrants from Taiwan profoundly influenced my path.

I vividly recall a childhood incident when my sister, suffering from asthma, faced a severe attack. The attending physician questioned our traditional Chinese herbal remedies instead of focusing on her immediate needs. This moment highlighted the crucial role of cultural sensitivity in healthcare and shaped my desire to connect deeply with patients and understand their unique backgrounds.

Like you, I navigated my medical education journey with resilience and the support of mentors. Here at Stanford Anesthesiology, we cherish the diverse stories and experiences our residents bring. We are steadfast in our commitment to fostering an environment where every voice is heard, every identity is respected, and every dream is nurtured.

Your journey from Columbia University to Stanford Anesthesiology is set against a backdrop of rapid technological advancement and social change. Here, you’ll find mentors who will champion your ambitions and a community enriched by every story, challenge, and dream.

We’re excited to welcome you to explore our program and look forward to co-creating the future of anesthesiology with you.

Warm regards,

Marianne Chen, MD Residency Program Director Stanford Anesthesiology

Five Questions for

Derek Smith, MD

Hometown: Born in Hamilton, New York. Grew up in Clinton, New York, and Brooklyn.

Medical School: University of California, San Francisco

Status: CA-1

How did you know Stanford was right for your residency?

I was attracted to Stanford because, in addition to many other subspecialties, Stanford has incredible pediatric and cardiac anesthesia programs, which are my primary interests. Essentially, I knew Stanford was the right place for me because of the intangible feeling of finding the program where I belong — the program where I would be supported in continuing to fight for equity, diversity, and inclusion, and the program where I could serve a broad and unique patient population during a vulnerable period.

What did you want to grow up to be? It may be cliché, but I’ve always known I wanted to be a doctor.

What has been your most impactful memory at Stanford so far?

Even with the improvements in diversity at Stanford and in the medical field as a whole over the last several decades, I’m still within the stark minority as a Black resident. The disproportionate underrepresentation of Black physicians is a fact that is painfully apparent to me, as it is to many of our patients. I was working with a Black patient from Oakland, California, in the ICU who was admitted with altered mental status and he quickly became obtunded. During the workup, widely metastatic recurrence of his cancer was discovered. Because of his mental status since admission, I never was able to speak directly with the patient, but became close to his wife and son. This was a family with limited health literacy, who was historically marginalized in health care, and separated from their loved one because of the pandemic. I became their eyes, ears and voice within the hospital, advocating for them. Despite the exhaustive efforts of the medical care team, the patient never regained consciousness. .... After he passed, the first thing the family said to me was, “Thank you.” Knowing that I’m from New York, they offered to be my West Coast family and return the love and support that I showed them.

How would you describe yourself in one word? Nurturing.

Favorite Netflix or Hulu pandemic binge?

“Alice in Borderland” on Netflix, with a very close honorable mention going to “Attack on Titan” on Hulu. SA

going where the science leads

BY TOM McGRATH

PHOTOS BY KRIS CHENG

A key National Institutes of Health grant will fund basic science research to figure out the mechanisms of pain. It could have significant impacts for patients and clinicians.

One day not long ago, Vivianne Tawfik, MD, PhD, an assistant professor in Stanford’s department of anesthesiology, perioperative and pain medicine, was a guest on a podcast when the subject of pain — or more accurately, the subject of pain’s subjectivity — came up.

As a pain researcher and clinician, Tawfik is deeply familiar with the personal nature of pain — and constantly challenged by it. Like many physicians, she explained to the host, she’d treated patients from various backgrounds, but every one of them experienced pain differently. Some would say their pain was so bad they had to spend 22 hours per day in bed, while others would report having equally intense pain — 10 on a scale of 1 to 10 — and yet still somehow function. There was no “typical” case. It was all as unique as a fingerprint.

At which point, as if on cue, one of the other guests on the podcast revealed that he’d been suffering from a severe migraine — a 10 out of 10 — throughout the entire episode. Tawfik shakes her head now, telling the story.

“I wouldn’t have known,” she says, “unless he’d said something.”

The irony, of course, is that despite her awareness of pain’s very subjective, personal nature, Tawfik has spent the bulk of her career trying to get a handle on what’s objective and universal about pain — that is, what the physiological mechanisms are that activate it. More specifically, she’s spent the last decade doing a deep dive into the role the immune system plays when the acute pain of, say, a surgical incision morphs into chronic pain that a patient just can’t shake, even after the original wound has long since healed.

It’s an area where Tawfik and the team in her lab have done significant work, and is one reason she was recently awarded an R35 grant from the National Institutes of Health (NIH)’s National Institute of General Medical Sciences. The grant will support Tawfik’s continued basic science research on what’s happening inside of our bodies when we feel pain — and what might alleviate it.

“I think of it as the early investigative rock star grant,” says Sean Mackey, MD, PhD, chief of Stanford’s pain medicine division.

“It’s a way of providing a young, talented, promising investigator with a stable supply of funding that is an

investment in their future. What the NIH is saying is, ‘We believe in this person.’”

ENDLESS CURIOSITY

Tawfik appreciates the endorsement and continues to be fascinated by the area she’s studying. “Pain is so mushy, in a way,” she says, returning to the topic of its subjectivity. “It’s kind of the opposite of what a scientist would want to study. It’s fuzzy, right? All these things influence it. But that’s also what makes it endless in terms of possibilities.”

Chatting via Zoom one morning, Tawfik notes that she wears many hats in her life. She’s a practicing clinician, spending one day per week seeing patients at Stanford’s Pain Management Clinic. She’s a researcher running her own lab and working side-by-side with a team of post-docs, PhD students and residents. She’s a mentor and educator, directing Stanford’s Fellowship in Anesthesia Research and Medicine (FARM) program.

“I’m also a mom,” she adds, confiding that, her multi-colored Zoom background notwithstanding, she’s doing the interview from her 4-year-old’s bedroom. “I’m actually surrounded by toys, which is why I have a virtual background on. There’s, like, Legos behind me.”

While Tawfik plays some disparate roles, those of pain physician and pain researcher complement each other well, at least most of the time. Sometimes, she says, she’ll successfully use a new treatment on a patient at the pain clinic, which will make the scientist part of her brain eager to understand the mechanism behind it. On the flip side, consistently seeing real people dealing with pain — and sometimes not being able to provide any relief to them — is a

constant reminder to keep pushing on the research front.

“Having someone in front of me and having to say to them, ‘I have no option for you’—that’s really motivating for when you’re in the lab,” she says.

It’s not to say the juggling is easy. “The challenge is, you’re only one person, but you have to do two separate jobs, and in some ways the two jobs don’t care about each [other],” says Tawfik’s colleague Paige Fox, MD, PhD, an assistant professor of surgery at Stanford who also runs her own lab. She and Tawfik have conferred on research and patients over the years.

“Your patients don’t care that you have a lab to run, and the lab that you have to run in some ways doesn’t care that you have patients to take care of,” Fox says. “But the benefit is, you really know what the critical questions are to answer.”

Tawfik, Fox says, has done a superb job balancing the two roles.

Looking at Tawfik’s CV, it might seem like she was on track to be a pain physician from the time she was a teenager. As a second-year undergrad at McGill University in Montreal, she worked for a pain physician, writing and doing research on the effects of cannabis on pain. At Dartmouth, where she earned her medical degree, along with a PhD in neuroscience, she apprenticed alongside pain researcher Joyce DeLeo, PhD

As a resident at Stanford, Tawfik was a participant in the FARM program she now directs, then did a subspecialty fellowship in pain medicine. But Tawfik insists her journey wasn’t as orderly and preordained as it might appear. She was born in Toronto, raised in Montreal, and was initially interested in studying addiction. It was a byproduct of her teenage years

Ultimately, the goal is to improve human health, to improve the care of chronic pain.

~ vivianne tawfik, MD, PhD

hanging around the latter city’s vibrant rave scene in the 1990s.

“I was always a nerd. I never did any drugs,” she says. “But I hung with a lot of kids who were trying Ecstasy and all these things that were popular at the time. And I was just fascinated from a neurochemical perspective. What’s it doing to the brain? Why are people so addicted to cigarettes? Because everyone in Montreal smoked at that time.”

If Tawfik’s original notion was to become an addiction psychiatrist, working in those various pain settings over the years made her understand the relationship between addiction and pain — well before the opioid crisis would make the connection clear on a broader scale. Eventually, she decided to shift her focus to understanding and treating chronic pain.

WHAT’S A GLIAL CELL TO DO?

Chronic pain is a chronic problem. One in three Americans suffers from it, though there remains much about it we don’t understand. Tawfik believes there are numerous reasons for that, beginning with that nettlesome issue of pain’s “mushiness.” Not only is it a challenge when dealing with the patients, but it also impacts basic science research in lab animals. Mice, for instance, can’t report their pain, and so researchers have to use surrogate measurements — traditionally, reflexes — to judge whether an animal subject is experiencing physical distress. Beyond subjectivity, there’s pain’s complexity, even compared with other neurological conditions. “When you think about Alzheimer’s or Parkinson’s, people die from those,” Tawfik says. “But people don’t die from pain. They die with pain.

“Pain is much more multifactorial and complex,” she continues. “Pain

is this one word, but it represents so many different conditions.”

She notes that back pain alone, for example, is said to have 50 different causes.

Much of Tawfik’s research over the years has focused on complex regional pain syndrome (CRPS), which she sees as an excellent way to look at how acute pain morphs into chronic pain. Exactly what qualifies as chronic is subjective, though generally it’s pain that last longer than three to six months.

“We’re pretty good at treating acute pain,” Tawfik says. “But when it becomes chronic, that’s when things become more complicated.”

Indeed, from a physiological perspective, acute pain is fairly straightforward: When an injury occurs, immune cells rush to the site of the trauma; neurons are activated; and pain signals are sent to the brain. As the wound heals, the neurons are deactivated and the pain eventually disappears. In patients with chronic pain, in contrast, the neurons continue to fire even after an injury heals.

In trying to understand why that happens, Tawfik and her colleagues have focused on two types of glial cells in the spinal cord — microglia and astrocytes. When all is working properly, microglia serve as something of a cleanup crew, eating up problem cells in the central nervous system, while astrocytes orchestrate how various neurons behave. In those who suffer from chronic pain, however, research from Tawfik’s lab has shown that the two types of cells behave abnormally: Both spew out inflammatory substances, for example, while astrocytes get distracted from coordinating the activity of neurons, causing signaling to change.

Can anything be done about that? Potentially. Tawfik and her team have done research in which they were

able to block certain pain receptors, which in turn deactivated some of the glial cells, decreased inflammation and reduced the sensation of pain. At least they did in mice.

“It seems,” Tawfik says of the glial cells she’s been studying for a decade, “like they play a key role in the transition from acute pain to chronic pain.” Whether that can one day lead to a treatment remains to be seen.

“[Tawfik’s] work falls between two fields — neurology and immunology,” says Mackey. But that, he notes, is exactly why it’s relevant and significant.

AN EYE ON THE PRIZE

In August 2020, Tawfik was awarded the R35 grant. In contrast to many research grants, which fund specific studies with particular expected outcomes, the R35 grant is more open-ended. “You’re proposing general concepts, but they’re funding you as an investigator,” Tawfik says.

The R35 grant will, as Tawfik puts it, let her and her team “go where the science leads. To me that’s the most amazing thing. That’s where the great discoveries are made.”

Initially, Tawfik’s work will focus on three specific areas: Trying to understand how the various types of glial cells in the central nervous system are different and how they cause inflammation; taking a deeper look at macrophages, blood cells that play a role in the pain process; and investigating whether different bone-healing treatments change pain outcomes.

The macrophage research is being done in collaboration with Michelle James, Ph.D, an assistant professor in the radiology department, while the bone study is being done with orthopedist Stuart Goodman MD, PhD

The goal of the research — of all of Tawfik’s research, in fact — is to lay the groundwork for protocols that

could one day help patients eliminate, or at least better manage, chronic pain. The journey from basic science research in mice to safe, effective treatments in humans is long and filled with plenty of potential potholes and wrong turns, but Tawfik tries to keep her eyes focused on the bigger prize.

“Ultimately, our goal is to improve human health, to improve the care of chronic pain,” she says. “We’re using mouse models to do that, but we’re not trying to cure mouse pain.”

As the interview wraps up, Tawfik is given a final, more philosophical question. Harking back to her statement about pain having many different meanings, it’s pointed out that it’s not just physical — at least in English, individuals use that same word for everything from a bump on the head to the emotional impact of a relationship ending. Does she ever ponder that?

“I’m a French-[speaker,]” she says after a moment, “and I’m trying to think in French how I would describe things. Yeah, I wouldn’t use the word ‘pain’ if I was sad that somebody wronged me or left me.”

But then she adds, summing up both the challenge of her work and why any triumphs in this area can be so profound, “I always say pain is like this four-letter word that I hate, because it’s totally non-specific. Everyone who comes to my clinic has pain, but everyone who says it means something different.”

Tawfik may be the one to help further define it. SA

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