Metabolite signaling & transport
My work identified Lac-Phe as a mediator of metformin’s effects on food intake and body weight, and MCT6 as an intestinal exporter that couples local metabolite production to systemic activity.
Postdoctoral Fellow · Stanford University
Chemical messengers. From metabolism to physiology.
I study the small molecules that connect cellular metabolism with whole-body physiology, combining molecular mechanisms with discoveries from nature’s extreme adaptations.
Research at a glanceChemical signalingEnergy balanceComparative physiology
01 / About
Decoding the language
between organs.
I’m Shuke Xiao, PhD, a postdoctoral fellow in Jonathan Z. Long’s laboratory in the Department of Pathology at Stanford University School of Medicine. My research asks how chemical messengers coordinate communication between organs and regulate feeding and energy balance.
I earned my PhD at Yale University with John R. Carlson, studying smell and taste in Drosophila, and my BS in Biological Sciences at Nanjing University. At Stanford, I combine metabolomics, biochemical assays, and mouse genetics with comparative physiology to discover signaling metabolites and define how they are made, transported, and sensed.
NIH K99/R00 Pathway to Independence Award recipient · 2025–2030
02 / Research
From molecules to physiology.
Discovering chemical messengers and the molecular machinery behind their biosynthesis, transport, and signaling.
Extreme physiology as a discovery engine
Studying the dramatic feeding response of pythons revealed pTOS, a conserved metabolite that activates hypothalamic neurons and suppresses feeding in mice. My future program will extend this approach to hibernation and other specialized adaptations.
Chemical modifications & biological function
I investigate how modifications of primary metabolites generate new biological signals. My writing examines lactate-derived modifications on proteins and metabolites; future work will explore how sulfation shapes metabolite transport and signaling.
03 / Publications
Selected discoveries & reviews.
Discoveries in metabolite signaling and transport, with their significance for physiology and future research.
Cell · In press
MCT6 is an intestinal Lac-Phe exporter required for metformin-associated weight loss
I identified MCT6 (SLC16A5) as an intestinal Lac-Phe exporter. Biochemical and genetic studies showed that MCT6 is required for normal circulating Lac-Phe levels, particularly after metformin treatment or intense exercise. Mice lacking MCT6 globally or in intestinal epithelial cells resisted metformin-associated weight loss; administering Lac-Phe rescued the phenotype.
Why it matters. This work establishes cellular export as a critical step linking intracellular metabolism to a circulating signal, and motivates my future search for transporters that control chemical messenger release and uptake.
Read preprint ↗No link suppliedNature Metabolism · 2026
Python metabolomics uncovers a conserved postprandial metabolite and gut–brain feeding pathway
Using untargeted metabolomics, I found that pTOS rises more than 1,000-fold after a meal in pythons. This microbiome-dependent, tyrosine-derived metabolite activates ventromedial hypothalamic neurons in pythons and mice. In mice, these neurons are required for its appetite-suppressing effects, and chronic treatment reduces food intake and body weight. pTOS also rises after meals in humans.
Why it matters. The study reveals a conserved gut–brain feeding pathway and demonstrates how extreme physiology can uncover chemical messengers, providing a foundation for my future research on sulfated signaling molecules.
Read paper ↗Annual Review of Biochemistry · 2026
Lactate as a chemical modification on proteins and metabolites
A review of the detection, regulation, and biological functions of lysine lactylation and N-lactoyl amino acids.
Why it matters. This review brings protein lactylation and metabolite N-lactoylation into a shared biochemical framework, showing how lactate-derived modifications can translate changes in glycolytic flux into downstream biological effects. It connects their detection, enzymatic regulation, and functions, and highlights unresolved mechanisms linking metabolism to cellular and organismal homeostasis.
Read review ↗Nature Metabolism · 2024
Lac-Phe mediates the effects of metformin on food intake and body weight
I found that metformin increases Lac-Phe in cells, mice, and two independent human cohorts. Metformin drives its production through complex I inhibition, increased glycolytic flux, and intracellular lactate. Intestinal epithelial CNDP2+ cells are its principal source in vivo. Mice lacking Lac-Phe biosynthesis resisted metformin’s effects on feeding and body weight; human cohort analyses supported Lac-Phe as a downstream mediator.
Why it matters. This work identifies a mechanism by which a widely used medicine amplifies an endogenous metabolite messenger, connecting metabolic chemistry with organismal energy balance.
Read paper ↗More publications 10 additional works
- A small molecule PTER-selective inhibitor reduces food intake and body weight
Fu S, et al. · Cell Chemical Biology · 2026
- A key role of PIEZO2 mechanosensitive ion channel in adipose sensory innervation
Wang Y, et al. · Cell Metabolism · 2025
- SLC17A1/3 transporters mediate renal excretion of Lac-Phe in mice and humans
Li VL, Xiao S, et al. · Nature Communications · 2024
- PTER is a N-acetyltaurine hydrolase that regulates feeding and obesity
Wei W, et al. · Nature · 2024
- Lac-Phe (N-lactoyl-phenylalanine)
Xiao S, Li VL, Long JZ · Trends in Endocrinology and Metabolism · 2024
- Meeting a threat of the Anthropocene: Taste avoidance of metal ions by Drosophila
Xiao S, Baik LS, Shang X, Carlson JR · PNAS · 2022
- Robust olfactory responses in the absence of odorant binding proteins
Xiao S, Sun JS, Carlson JR · eLife · 2019
- The diverse small proteins called odorant-binding proteins
Sun JS*, Xiao S*, Carlson JR · Open Biology · 2018
- PIAS3-mediated feedback loops promote chronic colitis-associated malignant transformation
Ma J, et al. · Theranostics · 2018
- A novel pyrazole-containing indolizine derivative suppresses NF-kB activation and protects against TNBS-induced colitis via a PPAR-dependent pathway
Fu Y, et al. · Biochemical Pharmacology · 2017
04 / Training & recognition
A path across disciplines.
From sensory neurogenetics to molecular and comparative physiology.
Education & training
2022–present
Stanford University
Postdoctoral Fellow · Advisor: Jonathan Z. Long
2016–2022
Yale University
PhD · Advisor: John R. Carlson
Thesis: Drosophila Chemoreception and Threats of the Anthropocene
2012–2016
Nanjing University
BS, Biological Sciences
Fellowships & selected awards
- NIH K99/R00 Pathway to Independence Award2025–2030
- Wu Tsai Human Performance Fellowship2025–2027
- American Heart Association Postdoc Fellowship2024–2025
- Stanford School of Medicine Dean’s Fellowship2023–2024
- First Place Oral Presentation Award, CADA2026
- People’s Choice Poster Award, Keystone – Solute Carriers2026
- Charles B. Carrington Memorial Award, Stanford Pathology2025
- Spangler Award for outstanding PhD thesis, Yale2022
Teaching & mentorship
I have taught courses and labs at Stanford, Yale, and Nanjing University, spanning human performance research, neuroanatomy, biochemistry, cell biology, genetics, and model organisms. At Stanford, I mentor rotation students, graduate students, and research staff. I also mentor local community college students through the Stanford Small Groups program.
Selected recent talks
University of Utah · Center for Metabolic Health Rising Stars Symposium · September 2026
UT Southwestern · SiNaPS Seminar Series · Invited speaker · June 2026
Frontiers in Diabetes Research Symposium · Invited speaker · May 2026
05 / Contact
Good science starts
with a conversation.
For research collaborations, scientific conversations, and speaking opportunities.
Department of Pathology
Stanford University School of Medicine
Stanford, CA 94305
skxiao@stanford.eduGoogle ScholarView profile ↗LinkedInView profile ↗Stanford University School of Medicine
Stanford, CA 94305