Michelle Hsiang is a UCSF Associate Professor in the Epidemiology and Biostatistics, with a secondary appointment in the Department of Pediatrics, Division of Pediatric Infectious Diseases, and a Chan-Zuckerburg Biohub Investigator. She serves as the Director of Research for the Malaria Elimination Initiative, and Co-Director of the Center for Infectious and Parasitic Diseases at the Institute for Global Health Sciences.
Dr. Hsiang recently received a K24 Midcareer Investigator Award from National Institute of Allergy and Infectious Diseases (NIAID). She recently spoke with Steven Birenbaum about the award and what it means for her work mentoring early career researchers in global health. This interview has been edited for length and clarity.
IGHS: You recently received a K24 award from NAID. Congratulations. What is a K24 award, and what is your award specifically for?
Hsiang: Thank you. The K24 is the National Institute of Health’s Midcareer Investigator Award in Patient-Oriented Research. It provides protected time to mentor the next generation of independent investigators, as well as support to expand my own research into new areas.
IGHS: Is it unusual to have an award that combines those two things?
Hsiang: Yes. Most NIH awards fund a specific project. Training grants exist, but they often are awarded for programs. The K24 is awarded to an individual and provides substantial protected time for mentoring. Clinician-scientists bring a unique perspective, but balancing both roles, plus teaching, mentoring, and administrative responsibilities, is difficult. The K24 offsets some clinical time and pressure to be constantly grant-writing, which can make it hard to innovate as a researcher and prioritize mentoring.
IGHS: The protected time allows mentoring to become a more central part of your work.
Hsiang: Exactly. It makes mentoring part of my core mission. I have specific targets for the number of people I will train and a plan to recruit them. I’ve partnered with the adult and pediatric infectious diseases fellowship directors and connected with other training programs. The award also brings more intentionality to training. I developed a specific plan for recruitment and training, including how I create individual development plans with trainees, a schedule of regular check-ins, and goals tailored to trainees at different levels. Designing and delivering on that plan is very different from simply having trainees attached to existing research projects.
The grant also leverages two ongoing NIH-funded clinical trials, giving trainees the opportunity to use those datasets and samples to ask new questions. Building a clinical trial and a cohort of participants who are followed closely over time takes enormous effort, and the result is an exceptionally rich resource. The trial answers the primary question—does this intervention work—but it can also answer many others that can support a trainee into their own career path as an independent researcher.
IGHS: Why is support for mentorship particularly important now?
Hsiang: One argument I made in my application was that we’re seeing declining interest among trainees in infectious diseases and global health. Much of that reflects the current funding and political climate surrounding global work. Many students and early-career investigators are wary of entering these fields. They see their mentors struggling, and I know many colleagues who have left the field, because they couldn’t keep their positions or secure funding. Between financial pressures and limited opportunities, trainees are being discouraged from pursuing this career path. That’s why it’s so important for mentors to have the bandwidth to support them. Trainees need to be inspired and supported, and they need to see that it is possible to pursue this path, succeed, and make a difference.
IGHS: Is the award a signal to the field that this career path can survive?
Hsiang: Absolutely. It’s an investment in the people who will carry this work forward. Another mentor of mine, who was our Pediatric Infectious Diseases Division Chief at the time, Maggie Feeney, also had a K24. When I was at a career transition, moving from my early faculty years toward an in-residence position, she guided me through the entire process, from preparing myself as a candidate to navigating negotiations. Mentorship isn’t only about research; it’s also about career development.
IGHS: The timing of this award is at mid-career. Is that unique?
Hsiang: Yes. The award is designed for investigators at the Associate Professor level. The idea is that you have enough experience to mentor others effectively, but you’re not so far along that you no longer have room to grow yourself. I’m excited about it, because I’m at a transition point in my career. As an Assistant Professor, I tended to see trainees as part of my team, helping to advance my work. Now I recognize that, like everyone, I have limited time and can only accomplish so much on my own. I see it as my responsibility—and a real source of satisfaction—to foster the continuity and sustainability of our field.
IGHS: What have you learned from your own mentors that you hope to pass along?
Hsiang: Everyone’s career path will be different. A good mentor helps trainees recognize the opportunities that will take them to the next step and beyond. Early in my global health training, I was very focused on working in China. I’m Chinese and had lived there, and I wanted my work to connect to my background. I did some work there, but malaria was rapidly disappearing from China during my training, so there were limited opportunities.
Early on, one of my mentors helped me see the difference between saying, “I want to work in China,” and developing expertise as a researcher. Being a researcher means building expertise where there’s a gap in knowledge. Around that time, an opportunity arose in Eswatini, which I initially saw as a side project. But comparing the two sites in terms of the scientific gaps and my preliminary data from Eswatini and China, the scientific story in Eswatini was much stronger. I pursued that work and went on to work in Southern Africa for many years.
IGHS: Did your mentors have different approaches?
Hsiang: Yes, and that’s important as a mentee. Different mentors bring different experiences, skill sets, and styles. For example, in global health one approach is to be deeply invested in a single geography. Another might work across many geographies around the world, bringing subject-matter expertise to each site. Seeing different approaches helps you decide what works best for you.
IGHS: Does mentorship extend to navigating life outside of research?
Hsiang: Absolutely. Especially for women, there’s the question of how to raise a family and have young children during what can be the most demanding stage of a career. My kids are now 10 and 13, but my training and early faculty years were a very challenging period. I was working and traveling a lot while also being a mother and supporting my husband in his academic medicine career. Having female mentors is important for women investigators, because there are distinct challenges. I could write a book about expressing breast milk while doing global health fieldwork!
IGHS: What scientific or clinical questions are you hoping to address with the K24?
Hsiang: The project builds on two clinical trials. The first is CHILD – Child Health and Infection with Low-Density Malaria. In that trial, we’re evaluating whether there’s a benefit to detecting and treating chronic, low-level persistent malaria infection in children. The traditional paradigm has been to treat children who present with illness, rather than those considered “asymptomatic.” I hesitate to use that term, because these children may experience more subacute or chronic negative health impacts from malaria infection.
The trial is in Tanzania and grew out of my work with the Malaria Elimination Initiative, where we’ve studied low-level chronic malaria from a transmission standpoint. Humans are the reservoir for most human malaria, so treating that reservoir can interrupt transmission and potentially eliminate the disease. As a pediatrician, I’ve long wondered whether there’s also a health argument for treating these infections—not just a transmission argument. Some argue that low-level infection protects against future malaria by sustaining anti-disease immunity. But in lower-transmission settings, that argument is weaker, and persistent low-level infection may be harmful.
IGHS: What kinds of effects are you looking at?
Hsiang: One question is how these low-level infections interact with other infections. Prior evidence suggests that chronic malaria infection increases susceptibility to non-malarial infections. To examine this question, we’re incorporating metagenomic next-generation sequencing, an unbiased approach to pathogen detection. We have samples from every febrile episode, along with detailed clinical data on each child over two years. That allows us to characterize the non-malarial infections children experience and ask whether clearing chronic malaria changes their risk for these infections.
We also want to understand what causes someone to become ill from malaria. Is it acquisition of a new strain, or a prior strain that was not treated or was treated but did not clear due to drug resistance? And what determines whether someone becomes symptomatic or experiences other malaria-related morbidity, such as anemia, impaired growth and cognition, or increased risk of other infections? These genomic methods help us understand not only the epidemiology of malaria in these settings, but also the mechanisms by which these interventions might work.
IGHS: What is the second trial?
Hsiang: The second trial focuses on malaria elimination. It’s in Peru and targets Plasmodium vivax. It’s called FLAME – Focal Mass Drug Administration (MDA) for Vivax Malaria Elimination. We’ve previously conducted several MDA trials with P. falciparum, mainly in sub-Saharan Africa. But outside sub-Saharan Africa, the predominant malaria species is P. vivax. No trials have specifically evaluated treating asymptomatic vivax infections to reduce transmission and achieve elimination.
The argument may be even stronger for vivax because, unlike falciparum, vivax has a dormant liver stage for which we have no diagnostic test. People can remain asymptomatic and then relapse months or even years later. We’re using a drug called tafenoquine, which has the advantage of being a single dose, compared with seven to 21 days of treatment with other regimens.
IGHS: Is treating these dormant infections important for elimination of vivax?
Hsiang: We think so. What’s striking about vivax is that modeling suggests many of the infections seen in clinics may be relapses—in some settings, perhaps as many as 90 percent. Those are model estimates, so we don’t know for certain. But if dormant infections are driving most transmission, then we have to target dormancy, which requires different treatment than blood-stage infection. Understanding the extent to which relapse drives transmission tells us where to focus interventions.
IGHS: Ultimately, how do you hope this research will improve care or outcomes for patients?
Hsiang: My work is at the applied end of the research spectrum. Through these trials, I’m evaluating existing tools in new ways. I hope the evidence we generate will, in the medium to long term, improve the health of individuals at risk for malaria and of their communities. In the CHILD study in Tanzania, an important component is neurocognitive outcomes and schooling. We’re investigating whether chronic malaria is linked to cognitive outcomes, which could affect overall well-being and economic productivity. Our goal is to reduce not only malaria itself, but also its broader health impacts.
In Peru, vivax malaria is sometimes considered less serious because it isn’t the main cause of malaria deaths—falciparum is. But vivax causes frequent relapses, and each one can leave a person very ill and unable to work or attend school for one or several weeks. It can also cause chronic effects such as anemia and adverse pregnancy outcomes, and it may affect cognition, although that hasn’t been well studied. Vivax was eliminated from the United States and many other countries, and we have the tools to detect, treat, and prevent it. Applying those tools can meaningfully improve the health and well-being of populations.
IGHS: Looking ahead, what would make you feel the award has been a success?
Hsiang: The award focuses mainly on training clinician-investigators to become independent researchers. Of course, it may not make sense for everyone I mentor to pursue a research career. But I would be pleased if within these five years, at least one outstanding clinician-scientist that I mentor advances to the next stage, by receiving a K career development award or a faculty position. This would indicate that I’ve helped to sustain and advance research in global health and infectious diseases.