I completed my B.S. in School of Life Sciences at Tsinghua University, China. I came to the USA for my Ph.D. studies at UT Southwestern Medical Center around seven years ago. My dissertation, a natural outgrowth of my enduring and broad interest in understanding how physiological systems interact during human diseases, focus on the mechanisms of synonymous mutations in determining protein expression, structure, and function, to explain certain human genetic diseases (circadian disorders and cancer progression).
My fascination with human physiology and pathology started at a young age, as I had a chance to have a lab tour at that time and my interest in Biology and Chemistry germinated. Such motivation instilled in me greater when I took college-level classes of Chemistry in my high school. That was the first time when I heard about the outbreak of Avian influenza and got resonated by the dedicated medical organizations and personnel around the world have taken to study this virus. Since then, I have set my career goal as addressing medical problems and developing novel therapeutics to improve people’s lives.
As a CIHMID postdoctoral fellow at Cornell University, I seek to fully explore the role of gut microbiota-derived metabolites in different physiological contexts. I investigate immunology-related area that involves characterizing how microbial metabolites from the gut microbiome can regulate the host immune system and help fight against pathogen colonization.
During my postdoc research, I have developed a pipeline for MS-based targeted metabolomics, by which I have systematically characterized the profiles of active microbiota-derived metabolites from different invitro cell culture, different diet and disease models. As metabolomics has emerged as a technique that focuses on defining the physiological and functional status of host-microbial interactions in biological contexts, such as urine, feces, and tissues. Therefore, it is a powerful method in gut microbiome or even metabolic-related fields that explore disease-related metabolites or dysregulated metabolic pathways. This work is a fundamental step towards engineering gut microbiota both in vitro and in vivo, and it would allow for an exhaustive analysis of the gut microbiota combined with the use of other methods including high-throughput sequencing techniques.
Emerging evidence suggests that the gut microbiome, a remarkably diverse ecosystem, can influence the host immune system mediated by microbial metabolites. Given that there is currently limited knowledge of complex host-gut microbiota interactions, my work will determine the diverse metabolic capabilities of these gut microbes and important functions of microbial metabolites on regulating gut homeostasis. Ultimately, the elucidation of the molecular mechanisms responsible for the effects of novel metabolites in host immunity and gut microbiota balance will provide novel targets for prophylactic and therapeutic approaches for various gut diseases.
After my CIHMID fellowship, I plan to find a position in academia.
RESEARCH: Transcriptional profiling of HIV-1 infected human alveolar macrophages by single-cell RNA sequencing
Macrophages are susceptible to HIV-1 infection and are resistant to virally-induced cell death. Alveolar macrophages (AM) in particular are known to be extremely long-lived and self-renewing, and have been shown to be both permissive to HIV-1 infection and persist in the face of Anti-Retroviral Therapy (ART) suppression. Indeed, they have been found to express HIV-1 RNA in virally-suppressed individuals. During HIV infection, the human lung becomes hyper-susceptible to Lower Respiratory Tract Infections (LRTIs) such as tuberculosis (TB), the major cause of death of those living with HIV.
To better understand how HIV infection impairs human lung immunity, we use single cell RNA-sequencing (scRNA-seq) approaches to analyze the host transcriptional profiling of macrophage populations from HIV-1 infected individuals who are ART-suppressed and those that are ART-naïve.
This project exploits recent technological advances to address considerable gaps in our appreciation of the significance of the alveolar macrophage as a haven for persistent HIV infection that is resistant to ART, and their role in the impairment of lung immunity.
Why do some gut bacteria stick to one host species, while others seem to hop around freely between them? What changes in their genomes when they move between hosts? And how can we begin to develop the data and tools we need to study these questions across the vast diversity of animal life? My work is centered on the idea that a comparative phylogenetic perspective can help us to navigate the incredible diversity and complexity of animal gut bacteria—and that recent advances in software and hardware automation give us the tools we need to tackle the problem in the non-model animal systems most useful for answering these fundamental questions. At CIHMID, I am focusing on implementing high-throughput microbial cultivation and sequencing, combined with long-read metagenomics, to reconstruct the genomic evolutionary history of gut bacteria in the deer mice, genus Peromyscus. By efficiently retrieving high-quality complete genomic information from thousands of bacteria across many host species, while simultaneously maintaining a living reference catalogue of these same bacteria, I hope to use phylogenomic analyses to identify and in vitro and in vivo assays to test hypotheses about the genomic basis of host specificity in the mammalian gut microbiome.
Iris explores the ways that vertebrate hosts cope with infections from the diverse community of parasites they encounter throughout their lives. Specifically, she looks at signatures of selection on the immune genes of lizards, and correlate those signatures with the lizard’s parasite community. Iris is working in Tory Hendry’s lab.
Shaun’s research focuses on the development of sequencing technologies to better elucidate host-virus interactions using enteric viruses (rotaviruses and mammalian orthroreoviruses). By augmenting spatial transcriptomic sequencing platforms, he aims to understand how the host reacts to viral infections across space and time and how these reactions either make the host more or less susceptible to infection. Shaun is working with the Parker, and De Vlamninck labs.