Title: Professor and Chief, Division of Infectious Diseases and Global Medicine
Research Interests: Microbiome–pathogen interactions, Clostridioides difficile colonization resistance, bile-acid, amino acid, and carbohydrate metabolism, defined microbial consortia, and translational therapeutics; previous work in HIV integration, viral drug resistance, and gene-therapy vector safety.
Our Focus: We study how gut microbial communities prevent Clostridioides difficile infection. Using gnotobiotic mouse models, 16S and shotgun metagenomics, and targeted metabolomics, we identify the taxa and metabolic pathways that confer colonization resistance—then rebuild that resistance with defined microbial consortia.
Research Areas
Mechanisms of Colonization Resistance
Our laboratory investigates how specific members of the gut microbiota prevent Clostridioides difficile from establishing infection, particularly after antibiotic disruption. We integrate 16S rRNA sequencing, shotgun metagenomics, and metabolomics to map bacterial taxa and functional pathways correlated with protection. Moving beyond correlation, we use gnotobiotic mouse models colonized with defined human microbial communities to test causality—adding back prioritized microbes one-by-one to determine which are sufficient to restore colonization resistance. These experiments reveal microbial interactions, niche competition, and metabolic dependencies that drive ecological protection.
Microbial Metabolites in Host Defense
Metabolites are the functional language of the microbiome. We focus on bile acid, amino acid, and carbohydrate metabolism, all of which significantly influence C. difficile germination, growth, and toxin production. By combining targeted and untargeted metabolomics with microbial genetics and ex vivo assays, we define how microbial transformation of bile acids and amino acids shapes the intestinal environment—creating niches favorable to commensals and hostile to pathogens. These studies identify metabolic signatures predictive of susceptibility or resilience and provide a foundation for therapeutic modulation with probiotics, prebiotics, or small molecule analogues.
Rational Microbial Therapeutics
We translate mechanistic insights into defined microbial consortia—rationally assembled microbial communities designed to restore missing metabolic functions or ecological architecture in dysbiotic guts. This “synthetic ecology” approach bridges pre-clinical discovery and translational intervention. We test candidate consortia in gnotobiotic mice for efficacy and safety, with concurrent metagenomic and metabolomic monitoring to ensure reproducibility and mechanistic clarity. Ultimately, this work aims to deliver next-generation microbiome therapeutics that are mechanistically grounded, scalable, and clinically predictable—offering an improved alternative to non-specific fecal microbiota transplantation for recurrent C. difficile infection.
HIV & HCV Clinical Virology and Therapeutics
Prior to our current microbiome focus, our work included extensive investigation of viral pathogens—Human Immunodeficiency Virus infection (HIV) and Hepatitis C virus infection (HCV)—focusing on antiviral resistance, minority variant detection, and treatment outcomes. Highlights include the development of a sensitive sequencing method for HIV-1 minority variants. In HCV, we evaluated resistance-associated substitutions (RAS) in genotype 1 infections that failed direct-acting antiviral therapy. This clinical virology expertise continues to inform our translational microbiome work—especially when considering microbial–viral–host interactions in immunocompromised contexts.
For recent publications highlighting both microbiome and viral pathogenesis work, see the full list below.
Click here for a full list of publications related to Dr. Wang’s Research.
Past Research Focus: HIV and HCV Virology
Clinical Virology: HIV and HCV
Before the lab’s current focus on microbiome–pathogen interactions, Dr. Wang’s research centered on viral evolution, drug resistance, and translational virology. His team developed ultrasensitive sequencing methods to detect HIV-1 minority variants and analyzed how these low-frequency mutations influence antiretroviral therapy outcomes. In parallel, his group characterized resistance-associated substitutions (RAS) in Hepatitis C virus (HCV) genotype 1 infections that failed direct-acting antiviral regimens—work that helped refine retreatment strategies and deepened understanding of viral persistence. This clinical virology foundation provided both conceptual and technical frameworks—high-resolution genomics, rigorous experimental controls, and translational thinking—that now underpin the lab’s microbiome research.
Bridging Virology and Microbiome Science
Our earlier work in HIV and HCV taught us how pathogen genetics and host context intersect to determine infection outcomes. That perspective now informs our microbiome studies, where we examine how microbial communities and metabolites modulate susceptibility to C. difficile infection. The transition from viral genomics to microbial ecology reflects a consistent theme across our research: defining causality from complex biological systems to guide targeted, mechanism-based therapies.
Early Research Foundations
Dr. Wang’s scientific training began in biochemistry and enzymology under Dr. Charles Grubmeyer at Temple University, where he studied the enzymes involved in purine and pyrimidine salvage. This work established a rigorous foundation in mechanistic enzymology, kinetics, and quantitative biochemical reasoning—skills that underpin his current systems-biology approaches. As a postdoctoral fellow with Dr. Frederic Bushman at the University of Pennsylvania, Dr. Wang focused on HIV integration, viral latency, and gene therapy vector safety. He developed and applied high-throughput sequencing methods to map tens of thousands of HIV and retroviral vector integration sites across the human genome, defining how chromatin structure and transcriptional context influence integration targeting. This work not only advanced understanding of HIV persistence and antiretroviral resistance, but also informed the field of retroviral gene therapy, helping to assess insertional mutagenesis risks and improve vector design for safer therapeutic use. These formative experiences in enzymology, molecular virology, and gene therapy provided the conceptual and technical framework that now drives the Wang Lab’s current focus on microbiome-based mechanisms of infection resistance and translational therapeutics.