Emily Happy Miller, MD, PhD, assistant professor in the department of medicine, division of infectious diseases, and the department of microbiology and immunology, recently received her first “K” award from the National Institutes of Health, a highly competitive grant intended to help junior faculty members make the leap to higher levels of NIH funding and productive careers as independent researchers.

Here she talks about how she became a physician-scientist, her love of patient care, and some of the big questions in the world of virology post-Covid.

Tell us about the research being funded by your K award.

EM: We’re taking a forward-looking approach at coronaviruses. How can we use everything we've learned about SARS-CoV2 to go a step further and develop vaccines that could target lots of different coronaviruses—ones we know about, but also ones that might emerge down the road. The goal is that if tomorrow, a new coronavirus that's a major human pathogen emerges somewhere in the world, we're not reinventing the wheel.

What are some of the major challenges?

EM: Every virus needs some mechanism to bind to the host cell. The receptor for coronaviruses is called ACE-2, and all the therapeutics we were giving people earlier in the pandemic targeted that interaction. The problem is it's very specific to each coronavirus, and it changes over time. That's what we saw with each new variant. As we use the antibodies, and as people get vaccinated, the virus mutates and changes and adjusts, and that receptor is the hotspot of where it likes to adjust.

But there are other regions of the spike protein that are also important for getting the virus into cells. So we’re looking at those and trying to find commonalities between coronaviruses, and trying to find a new therapeutic target.

A pan-coronavirus vaccine could help us tackle our current problems, like the new variants of Covid that continue to emerge, but also future problems that we won't know about until they happen. We have to be proactive because if a new virus becomes a threat, we’ll need these strategies, and we’ll need them right away.

When did you know you wanted to pursue science?

EM: I knew I wanted to be a doctor from an early age. No one in my family was in a medical field, but even as a kid, you go to the doctor and get to see what a doctor is, and that's a tangible career. Scientist is a little bit harder to understand, and we don't do a great job highlighting that career path. In college at Loyola University Chicago they had a research fellowship where you worked in a lab during your summers. It was one of those things that absolutely changes your life. I immediately thought wow, this is really fun, but I also still want to be a doctor. My research mentor told me about MD-PhD programs. I hadn’t known that was an option. There were people who tried to discourage me, saying it's such a long haul. Unfortunately there was also a lot of, you're a young woman, you're never going to be able to have a family. But I trusted my instincts. This path made so much sense to me.

If I hadn't had that opportunity, I probably would have just gone to medical school. Maybe I would have ended up in the same place eventually, but I’m grateful the door to research was opened to me early on. That is how I ended up doing my MD-PhD at Albert Einstein College of Medicine.

What are some of the most important things you need to be successful in science?

EM: I always tell students that the most important thing is good mentorship. There is lots of science that's fun and interesting, but not everyone is going to be the right mentor for you, and that is absolutely essential and priceless.

When I was looking for labs here, I met Kartik Chandran at the faculty poster presentations. He was a relatively new primary investigator at the time. I chatted with him and found out he was studying Ebola. I had read The Hot Zone in high school, and that sounded exciting. But I also just really liked him. I decided to do my PhD in his lab more because he seemed like a great mentor and a good fit for me. I was only the second graduate student in his lab.

How has your research evolved over time?

EM: My PhD work was very much basic science. This was back in 2008, so before the really big Ebola virus outbreak in West Africa in 2015. It was very much about understanding the virus and what it is using to infect host cells. Once you know that, those are potential targets for antibodies or a drug, something you could use to treat the virus.

After graduating I did my residency at Columbia, followed by a fellowship in infectious diseases. During my second year of fellowship, the pandemic hit. It was a crazy time to be a New Yorker, a physician in New York, and certainly to be an infectious disease physician in New York, especially with a background in emerging viruses.

How did the pandemic impact your work?

EM: Like so many of us I was focused on caring for patients. Research at that time had to be essential research, which meant SARS-coV2. We noticed that in addition to respiratory symptoms, some patients had a lot of GI symptoms. Others had neurological symptoms. Was the latter because there was virus in the brain? Or was it because the virus sparks this huge immune response that can affect the entire body? You would treat those two things differently.

We started collecting samples of cerebral spinal fluid as well as brain samples from patients who had died from Covid. If the neurology team was doing a lumbar puncture on a Covid patient, I had a little rack in the neuro ICU of my tubes. I would inactivate the virus while preserving the RNA. I’d bring them back to our lab to see if we could detect virus in those samples. It was literally bedside-to-bench research.

It was very different from the research that I did for my PhD thesis. I've never seen an Ebola patient. It showed me what was possible in terms of bringing together the clinical side with the lab. I was someone who could live in both spaces and mediate that connection, and I felt that was a good spot for me.

You still actively see patients. Is it challenging to balance the clinical and research aspects of your work?

EM: I currently spend about seven weeks in the hospital on the infectious disease consult service, down from 10 before I had more research funding. We have an ID clinical conference with all the attendings and fellows at Weiler Hospital, and I always go to hear about what the interesting cases are. I love clinical medicine and seeing patients. I loved residency and fellowship and I worked really hard to develop those clinical skills. But patient care also informs my research. It's important to have an ear on the ground, so to speak.

What keeps you up at night?

EM: Once a virus is transmitting in humans, it's like trying to catch the wind. You'll never stop it. You can only hope to contain it and do your best to mitigate the damage. And so the dream is to stop it before it gets to that point. But we'll never get there until we really understand how viruses evolve from being animal viruses to human viruses.

One of the big questions I’m interested in is that in-between step. What does it take to get there?

Take bat viruses, for instance. We don’t have great tools to study these things in bats. You have to have live samples, which means you have to have special biocontainment equipment. But it’s also a moving target. It would require testing the genetic landscape. There are many little things happening along a continuum before it's now a human virus. There are multiple steps to evaluate, which you could then potentially target.

Understanding this process would also make us better at predicting which viruses we need to be worried about. Eventually, we might find a way to keep them from spreading to humans.