What inspired you to pursue aging research?
I am passionate about finding microbiota-targeted therapeutics that enhance healthy aging in our communities. I was first drawn to aging research during my graduate research at Stanford. I was fascinated by how the microscopic C. elegans worms that live for only three weeks can reveal fundamental knowledge of human aging. As I identified bioactive lipid molecules that can extend lifespan in worms and confer health benefits that can be extended to mammals, I was further drawn by the implications and relevance of my research to the aging population today. During my postdoctoral training, I embraced the fascinating world of the human gut microbiome, a key, and yet untapped source of small molecules whose functions are largely undefined. I dedicated four years to mapping out what these molecules are and which human gut bacteria are producing them. My next step in my new lab at Duke is to understand how they can benefit us, so we can harness their power to alleviate age-associated decline in the host.
In your view, what does AFAR mean to the field, and what does it mean, for you, to receive an AFAR grant now?
I first learned about AFAR’s initiative on supporting pioneer aging researchers during my graduate career through the AFAR/Glenn symposium at Stanford. I discovered that AFAR has been well-respected in the aging field as the organization that supports truly innovative research dedicated to extending the quality of human lives. Since this conference, I have aspired to join the ranks of the investigators recognized and supported by AFAR. As an early career investigator, I am honored to receive this AFAR grant, which will provide the critical support to turn an ambitious project into the cornerstone of our lab’s future research.
What is exciting about your research’s potential impact?
My research program will be impactful to the field because it builds upon an innovative technology of high-resolution mass spectrometry that enables the mapping of gut bacteria and host metabolites in the context of aging. Building on this technology, my vision goes beyond cataloging the metabolites to studying their biological impact on host models (e.g., C. elegans, mice). My lab’s research will pave the way for identifying molecular candidates for ameliorating age-associated decline in the host.
How would you describe your research to a non-scientist?
Recent advances in animal and human trials have revealed a surprising and exciting link between the gut microbiome and host healthspan. In particular, administering probiotic bacteria to colonize the gut successfully extends healthspan (e.g., gastrointestinal (GI) function, inflammation) and lifespan in the host. While this is an exciting, non-invasive therapeutic avenue, we do not know how gut bacteria impact different tissues (GI, blood). In the Han Lab, we study this critical but missing link between probiotic gut bacterial species and healthy aging in the host. Gut bacterial species can communicate with the host through the production of small metabolites. Some of these molecules subsequently enter the host circulation, reach different tissues, and impact diverse aspects of host physiology (e.g., Inflammatory Bowel Diseases, Alzheimer’s Disease). Therefore, understanding what molecules are produced by human bacteria provides the first step toward understanding how they may impact our health.
Using our lab’s newly established metabolomics pipeline, we recently identified the top candidate molecules that are 1) highly produced by several probiotic bacterial species and 2) detected in both bacteria and humans. We have also established several tools (metabolomics, gut bacterial culturing) and several host models (C. elegans, intestinal cell culture) to study their functions and health benefits to the host. Our study is important because understanding how bioactive bacterial molecules regulate host physiology provides molecular targets for delaying age-related diseases. Leveraging our lab’s expertise in the biology of gut microbiome and aging, coupled with a track record of making technological advances to accelerate small molecule discovery, the Han Lab is uniquely positioned to define the regulation of host aging and physiology by the gut microbiota.
