About

KC Huang is a LeRa Professor and Professor of Microbiology and Immunology at Stanford University. His laboratory employs diverse interdisciplinary methods of inquiry to understand the relationships among cell shape detection, determination, and maintenance in bacteria. Cell shape plays a critical role in regulating many physiological functions, yet little is known about how the wide variety of cell shapes are determined and maintained. Inside the cell, many proteins organize and segregate, but how they detect and respond to the cellular morphology to end up at the right place at the right time is also largely mysterious. The group uses a combination of analytical, computational, and experimental approaches to probe physical mechanisms of shape-related self-organization in protein networks, membranes, and the cell wall. Current topics of interest include cell-wall biosynthesis, the regulation and mechanics of cell division, membrane organization, and membrane-mediated protein interactions. Ultimately, the manipulation of cell shape may provide a direct tool for engineering complex cellular behaviors.

Research topics

• Biology
• Genetics
• Computational biology
• Computer Science
• Microbiology
• Ecology
• Cell biology
• Artificial Intelligence
• Data Mining
• Immunology
• Evolutionary biology
• Zoology
• Biochemistry
• Database

Selected publications

• The network structure of microbial cross-feeding impacts community diversity during antibiotic treatment

  Zenodo (CERN European Organization for Nuclear Research) · 2026-01-01

  otherOpen accessSenior author

  Antibiotics can reduce gut microbiome diversity, with negative health effects on the host, but predicting community diversity during antibiotic treatment is challenging due to the many mechanisms by which species interact. While both nutrient competition and cross-feeding can play major roles in microbiota assembly, the effect of antibiotics is often studied experimentally in monoculture, and theoretical studies have focused on communities that interact via nutrient competition alone. To investigate the interplay between nutrient competition, antibiotics, and cross-feeding, we introduce a consumer-resource model that includes all three interactions, and captures a wide range of cross-feeding network architectures with a single parameter. For three-species communities, we found that coexistence during narrow-spectrum antibiotic treatment was maximal with a cyclic cross-feeding network, while fully connected cross-feeding networks maximized coexistence during broad-spectrum antibiotic treatment. However, the effects of cyclic cross-feeding were particularly sensitive to community size and the number of targeted species (antibiotic spectrum); for communities with more than six species and resources, cyclic cross-feeding can be detrimental to coexistence due to instability. Our findings highlight the complex effects of cross-feeding network architecture on coexistence when growth inhibition reshapes the nutrient competition landscape, with potential applications to microbial communities in all natural environments, where they are often exposed to growth-inhibiting agents such as drugs, temperature, and pH modulation.

  PublisherDOI

• Microbiota and kidney disease: the road ahead

  UNC Libraries · 2026-05-02

  articleOpen access
  PublisherDOI

• Independent tuning of outer membrane fluidity and mechanics in Gram-negative bacteria

  Stanford Digital Repository · 2026-03-30

  datasetOpen accessSenior author

  The outer membrane (OM) of Gram-negative bacteria forms a protective barrier that combines selective permeability with mechanical load-bearing capacity, properties linked to its asymmetric bilayer structure with lipopolysaccharides (LPS) in the outer leaflet and phospholipids (PLs) in the inner leaflet. In contrast to lipid bilayers, the OM typically exhibits limited lateral diffusion, producing a gel-like surface with spatially organized proteins and LPS maintained by strong protein-LPS interactions. The molecular basis of this physical state and its relationship with envelope mechanics remain unclear. Here, we show that increasing PL levels in the outer leaflet or truncating LPS core oligosaccharides increases OM fluidity by disrupting LPS packing. In contrast, perturbations that reduce LPS abundance primarily reduce OM stiffness with little effect on fluidity. These results demonstrate that OM fluidity and mechanical stiffness can be tuned independently through distinct molecular interactions. This separation of physical control mechanisms provides a framework for understanding how Gram-negative bacteria modulate OM properties during environmental adaptation and envelope homeostasis.

  PublisherDOI

• On the growth and form of bacterial colonies

  Nature Reviews Physics · 2025-09-01 · 8 citations

  articleSenior author
  PublisherDOI

• Low-input RNA-seq suggests metabolic specialization underlying morphological heterogeneity in a gut commensal bacterium

  Cell Reports · 2025-06-01 · 4 citations

  articleOpen access

  Isogenic bacteria can be phenotypically diverse. This heterogeneity is evident in the Bacteroidota, a predominant phylum of the human gut microbiota. These bacteria adopt diverse morphologies, yet the molecular basis of their morphological heterogeneity is poorly understood. Here, we systematically characterize the variation in cellular morphology of Bacteroides thetaiotaomicron cells during laboratory growth and after isolation from different host niches. We develop a sensitive transcriptomics approach and apply it to B. thetaiotaomicron sorted into sub-populations of varying cell sizes. Differential expression analysis indicates metabolic specialization associated with morphology. Transcriptomic data also reveal morphological marker genes, whose size-dependent expression is validated through fluorescence in situ hybridization. Morphological characterization of deletion and overexpression mutants reveals that specific marker genes causally contribute to B. thetaiotaomicron cell-size determination. Since phenotypic heterogeneity is a common feature of microbial consortia, this study serves as a blueprint for understanding the role of bacterial genes in morphological variation.

  PublisherOA PDFDOI

• Abundance measurements reveal the balance between lysis and lysogeny in the human gut microbiome

  Current Biology · 2025-04-28 · 15 citations

  article
  PublisherDOI

• A molecular cell atlas of mouse lemur, an emerging model primate

  Nature · 2025-07-30 · 8 citations

  articleOpen access

  Abstract Mouse lemurs are the smallest and fastest reproducing primates, as well as one of the most abundant, and they are emerging as a model organism for primate biology, behaviour, health and conservation. Although much has been learnt about their ecology and phylogeny in Madagascar and their physiology, little is known about their cellular and molecular biology. Here we used droplet-based and plate-based single-cell RNA sequencing to create Tabula Microcebus, a transcriptomic atlas of 226,000 cells from 27 mouse lemur organs opportunistically obtained from four donors clinically and histologically characterized. Using computational cell clustering, integration and expert cell annotation, we define and biologically organize more than 750 lemur molecular cell types and their full gene expression profiles. This includes cognates of most classical human cell types, including stem and progenitor cells, and differentiating cells along the developmental trajectories of spermatogenesis, haematopoiesis and other adult tissues. We also describe dozens of previously unidentified or sparsely characterized cell types. We globally compare expression profiles to define the molecular relationships of cell types across the body, and explore primate cell and gene expression evolution by comparing lemur transcriptomes to those of human, mouse and macaque. This reveals cell-type-specific patterns of primate specialization and many cell types and genes for which the mouse lemur provides a better human model than mouse 1 . The atlas provides a cellular and molecular foundation for studying this model primate and establishes a general approach for characterizing other emerging model organisms.

  PublisherOA PDFDOI

• Non-antibiotics disrupt colonization resistance against enteropathogens

  Nature · 2025-07-16 · 30 citations

  articleOpen access

  Abstract Non-antibiotic drugs can alter the composition of the gut microbiome 1 , but they have largely unknown implications for human health 2 . Here we examined how non-antibiotics affect the ability of gut commensals to resist colonization by enteropathogens 3 . We also developed an in vitro assay to assess enteropathogen growth in drug-perturbed microbial communities. Pathogenic Gammaproteobacteria were more resistant to non-antibiotics than commensals and their post-treatment expansion was potentiated. For 28% of the 53 drugs tested, the growth of Salmonella enterica subsp. enterica serovar Typhimurium. ( S . Tm) in synthetic and human stool-derived communities was increased, and similar effects were observed for other enteropathogens. Non-antibiotics promoted pathogen proliferation by inhibiting the growth of commensals, altering microbial interactions and enhancing the ability of S . Tm to exploit metabolic niches. Drugs that promoted pathogen expansion in vitro increased the intestinal S . Tm load in mice. For the antihistamine terfenadine, drug-induced disruption of colonization resistance accelerated disease onset and increased inflammation caused by S . Tm. Our findings identify non-antibiotics as previously overlooked risk factors that may contribute to the development of enteric infections.

  PublisherOA PDFDOI

• Competition for shared resources increases dependence on initial population size during coalescence of gut microbial communities

  Proceedings of the National Academy of Sciences · 2025-03-10 · 23 citations

  articleOpen accessSenior authorCorresponding

  The long-term success of introduced populations depends on both their initial size and ability to compete against existing residents, but it remains unclear how these factors collectively shape colonization dynamics. Here, we investigate how initial population (propagule) size shapes the outcome of community coalescence by systematically mixing eight pairs of in vitro microbial communities at ratios that vary over six orders of magnitude, and we compare our results to neutral ecological theory. Although the composition of the resulting cocultures deviated substantially from neutral expectations, each coculture contained species whose relative abundance depended on propagule size even after ~40 generations of growth. Using a consumer-resource model, we show that this dose-dependent colonization can arise when resident and introduced species have high niche overlap and consume shared resources at similar rates. Strain isolates displayed longer-lasting dose dependence when introduced into diverse communities than in pairwise cocultures, consistent with our model's prediction that propagule size should have larger, more persistent effects in diverse communities. Our model also successfully predicted that species with similar resource-utilization profiles, as inferred from growth in spent media and untargeted metabolomics, would show stronger dose dependence in pairwise coculture. This work demonstrates that transient, dose-dependent colonization dynamics can emerge from resource competition and exert long-term effects on the outcomes of community coalescence.

  PublisherOA PDFDOI

• Assembly of stool-derived bacterial communities follows “early-bird” resource utilization dynamics

  Cell Systems · 2025-04-01 · 9 citations

  articleSenior author
  PublisherDOI

Recent grants

• A universal pipeline for functional characterization of the human microbiota at a massive scale

  NIH · $7.6M · 2020–2026

• NIH Grant DP2OD006466

  NIH · $2.4M · 2014

• MIM: Systematic Dissection of Complex Synthetic Gut Bacterial Communities

  NSF · $2.5M · 2021–2026

• Molecular Biophysics Training Program at Stanford

  NIH · $9.8M · 1989–2020

• NIH Grant K25GM075000

  NIH · $602k · 2010

Frequent coauthors

• Justin L. Sonnenburg

  Chan Zuckerberg Initiative (United States)

  78 shared

• Handuo Shi

  Stanford University

  77 shared

• Norma Neff

  Chan Zuckerberg Initiative (United States)

  55 shared

• Stephen R. Quake

  Stanford University

  50 shared

• Andrés Aranda-Díaz

  University of California, San Francisco

  49 shared

• Katharine M. Ng

  University of British Columbia

  48 shared

• Adam M. Deutschbauer

  Lawrence Berkeley National Laboratory

  47 shared

• Carolina Tropini

  University of British Columbia

  44 shared

Education

• Ph.D., Microbiology and Immunology

  Stanford University

  1996

• B.S., Microbiology

  University of California, Berkeley

  1991