About

Dr. Shili Xu is an Associate Professor in the Department of Pharmacology at the University of California, Los Angeles (UCLA). He holds a B.S. in Biological Sciences and a B.S. in Economics from Peking University, and a Ph.D. from the University of Southern California, where he studied small-molecule drug design and discovery. His postdoctoral research at UCLA focused on cell metabolism, molecular imaging, and synthetic lethality for cancer therapy in small animal models. Currently, Dr. Xu is the Director of Preclinical Imaging at the Crump Institute for Molecular Imaging and an Assistant Professor of Molecular and Medical Pharmacology at UCLA. His research team develops advanced in vivo molecular imaging technologies, including positron emission tomography (PET), computed tomography (CT), and optical imaging (fluorescence and bioluminescence). These technologies are applied for non-invasive assessment of cancer, immune response, neurological disorders, cardiology, and related biological processes, as well as for preclinical probe and drug development in small animal models. His work includes the development of a broad spectrum of PET probes and reporter genes to image cell metabolism, monitor cell trafficking and activation, track disease progression, and profile drug pharmacokinetics and pharmacodynamics.

Research topics

• Biology
• Internal medicine
• Cancer research
• Medicine
• Computational biology

Selected publications

• The liver regulates ectopic calcification in Abcc6-deficient models of pseudoxanthoma elasticum

  Journal of Clinical Investigation · 2026-03-10

  articleOpen access

  Pseudoxanthoma Elasticum (PXE) is a rare disease caused by loss of function of the ATP-binding cassette C (ABC) member 6 (Abcc6) gene and characterized by ectopic calcification of multiple tissues, but the physiological reasons underlying ectopic calcification in PXE remain unclear. In a murine model of Abcc6-deficient PXE in which animals developed robust cardiac calcification after heart injury, we show the critical importance of the liver in mediating ectopic cardiac calcification. Tissue-specific deletion of Abcc6 in the liver, but not in the heart, was sufficient to cause post-injury cardiac calcification. Metabolomics and gene expression analysis demonstrated deficiencies in nucleotide metabolism, cellular energetics, and defects in cellular respiration underlying ectopic calcification in PXE. Functional abnormalities in cellular respiration in the injured heart were similar in animals with global or liver-specific Abcc6 deficiency, showing that hepatic Abcc6 expression regulated cellular respiration in the injured heart. We show that ectopic calcification in PXE was primarily dystrophic and that treatment with clodronate or etidronate, which prevent the growth of calcium hydroxyapatite mineralization, was sufficient to rescue the phenotype of ectopic cardiac calcification in Abcc6-deficient states. Taken together, these observations highlight the role of the liver in regulating target tissue metabolic and mitochondrial function in causing ectopic calcification in Abcc6-deficient states.

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• Lentivirus-based HPSC therapy provides effective and long-term treatment in hypophosphatasia mouse model

  Molecular Therapy · 2026-03-01

  article
  PublisherDOI

• Retrospective Cardiac Gating with A Prototype Small-Animal X-ray Computed Tomograph

  Journal of Visualized Experiments · 2025-02-21 · 2 citations

  articleOpen accessSenior author

  The CrumpCAT is a prototype small-animal X-ray computed tomography (CT) scanner developed at our research institution. The CMOS detector with a maximum frame rate of 29 Hz and similar Tungsten X-ray sources with energies ranging from 50 kVp to 80 kVp are widely used across commercially available preclinical X-ray CT instruments. This makes the described work highly relevant to other institutions, despite the generally perceived wisdom that these detectors are not suitable for gating the high heart rates of mice (~600 beats/min). The scanner features medium- (200 µm) and high- (125 µm) resolution imaging, fluoroscopy, retrospective respiratory gating, and retrospective cardiac gating, with iterative or filtered-back projection image reconstruction. Among these features, cardiac gating is the most useful feature for studying cardiac functions in vivo, as it effectively eliminates image blurring caused by respiratory and cardiac motion. Here, we describe our method for preclinical intrinsic retrospective cardiac-gated CT imaging, aimed at advancing research on in vivo cardiac function and structure analysis. The cardiac-gating method acquires a large number of projections at the shortest practical exposure time (~20 ms) and then retrospectively extracts respiratory and cardiac signals from temporal changes in raw projection sequences. These signals are used to reject projections belonging to the high motion rate inspiration phase of the respiratory cycle and to divide the remaining projections into 12 groups, each corresponding to one phase of the cardiac cycle. Each group is reconstructed independently using an iterative method to produce a volumetric image for each cardiac phase, resulting in a four-dimensional (4D) dataset. These phase images can be analyzed either collectively or individually, allowing for detailed assessment of cardiac function. We demonstrated the effectiveness of both approaches of the prototype scanner's cardiac-gating feature through representative in vivo imaging results.

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• Real-Time <i>in Vivo</i> Bacterial Imaging by Computed Tomography and Fluorescence Using Phage-Gold Nanorod Bioconjugates as Contrast Agents

  ACS Biomaterials Science & Engineering · 2025-05-08

  articleOpen access

  Real-time in vivo imaging of bacterial infections is an important goal to aid the study and treatment of bacterial infections. Phages can be genetically engineered to ensure a particular biomolecular target specificity, and gold nanomaterials can be conjugated to phages for a variety of applications including biosensing. In this paper, we describe methods to use phage-gold nanorod conjugates for in vivo detection and imaging of the bacterial species Pseudomonas aeruginosa in mice. The imaging modalities are computed tomography (CT), using gold as a contrast agent, and fluorescence, which can be applied when the FDA-approved near-infrared (NIR) dye indocyanine green (ICG) is also chemically cross-linked to the bioconjugates. In addition, rapid protocols for validating bioconjugate synthesis and the initial assessment of toxicity are given. In this example, the phage-gold nanorod probe is shown to specifically highlight P. aeruginosa without cross-reactivity to another Gram-negative organism (V. cholerae) in vivo and appears to be biocompatible. Phage-directed imaging probes may thus be useful for the characterization and diagnosis of bacterial infections.

  PublisherDOI

• Bone Loss and <scp>TLR4</scp> Signals Contribute Independently to B Lineage Aging

  Aging Cell · 2025-10-11 · 2 citations

  articleOpen access

  B cell development declines with age, but how structural changes in the marrow environment contribute to that process is incompletely understood. Multiplexed volumetric imaging revealed that B lineage cells were enriched near bone, and trabecular bone in particular, in young mice. However, B cell progenitors were depleted from these regions in strains of old mice that exhibited senile osteoporosis. In striking contrast, the age-related decline of B lymphopoiesis was attenuated in mice in which bone mass was maintained over the lifespan and could be completely abrogated by concomitantly blocking TLR4 signaling. In addition to demonstrating that developing B lineage cells are not randomly distributed in the marrow, these results indicate that the age-related decline in B lymphopoiesis is influenced by the loss of salutary and not just an increase in inhibitory signals.

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• Three-Dimensional Printing of the Human Pericardium to Facilitate Understanding of the Pericardial Reflections, Recesses, and Sinuses

  Circulation Cardiovascular Imaging · 2025-08-27

  articleOpen access
  PublisherOA PDFDOI

• Supramolecular hydrogel actuators with reprogrammable magnetic orientation by locally mediated viscoelasticity and pinning force

  Science Advances · 2025-06-27 · 12 citations

  articleOpen access

  Magnetic soft actuators with reprogrammable deformations have gained substantial attention due to their adaptability for various applications. However, achieving precise and local reorientation of magnetic particles remains challenging. Here, we present a strategy to locally tailor the viscoelasticity of magnetic supramolecular hydrogels, facilitate reorientation of the embedded magnetic particles, and enable reprogrammable magnetoactuated deformation and locomotion of the composite gels. The magnetic hydrogels are facilely prepared by mixing neodymium-iron-boron particles with an aqueous poly(acrylic acid– co –acrylamide) solution, which spontaneously forms supramolecular network with carboxylic–ferric ion coordinates as physical cross-links. This network enables dynamic control of viscoelasticity by localized laser heating, which reduces the pinning force of gel matrix and allows for reorientation of magnetic particles under a modest magnetic field. We demonstrate that the same hydrogel sheet can be reprogrammed to exhibit various complex deformations and locomotion. This versatile approach to developing magnetic hydrogels with adaptive responses offers exciting potential for soft robotics and biomedical devices.

  PublisherDOI

• Er Miao San Attenuates Collagen-Induced Arthritis Mice by Regulating Gut Microbiota and Its Metabolites

  Journal of Microbiology and Biotechnology · 2025-11-26 · 1 citations

  articleOpen access1st author

  IntroductionRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation [1,2].Increasing evidence suggests that the gut-joint immune axis has a main role in the pathogenesis of RA [3], and imbalance in the host gut microbiota is a key contributing factor [4,5].Dietary modifications or pharmacological interventions are known to positively reshape the gut microbiota composition [6][7][8], which suggests the therapeutic potential of microbiota modulation for RA treatment.Meanwhile, traditional Chinese medicine (TCM) has demonstrated efficacy in treating various illnesses and is gaining attention.However, the complex composition and pharmacological mechanisms of TCM formulations require further investigation.Emerging evidence indicates that some of these medicines can significantly alleviate RA by modulating gut microbiota and its metabolites [9, 10], suggesting a promising avenue for research.Er Miao San (EMS) is a TCM formulation with demonstrated anti-inflammatory and immunomodulatory properties.Our previous research has shown that it exerts anti-RA effects by modulating dendritic cells, T cells, and macrophage polarization, as well as inhibiting the Wnt/-catenin pathway [11,12].The gut-targeting potential of berberine, a key component of EMS, is well known [13].Furthermore, some herbal compounds have been linked to the gut microbial short-chain fatty acids (SCFAs)-immune-modulation axis [14].However, it remains unclear whether the anti-arthritic effect of the entire EMS formula is superior to that of its individual components by being mediated through this mechanism.Therefore, in this study we investigated whether EMS exerts its therapeutic effects against RA, specifically through remodeling the gut microbiome and promoting the production of beneficial metabolites, to provide direct evidence for its gut-mediated mechanisms of action. Dysbiosis of the gut microbiota plays a key role in the pathogenesis of rheumatoid arthritis (RA).However, it is still unclear whether the classic prescription Er Miao San (EMS) can exert therapeutic effects on RA by regulating the gut microbiota.In this study, we investigated whether EMS alleviates collagen-induced arthritis (CIA) by modulating the gut microbiota and its metabolites.We demonstrated that EMS significantly reduced arthritis severity, paw swelling, and systemic inflammation in CIA mice.In addition, 16S rRNA sequencing analysis revealed that EMS restored gut microbiota homeostasis, as evidenced by an increased abundance of Bacteroidetes, and a decreased Bacteroidetes/Firmicutes ratio.Crucially, antibiotic depletion of the gut microbiota abolished the protective effects of EMS, whereas fecal microbiota transplantation (FMT) from EMS-treated donors replicated its anti-arthritic efficacy, confirming the indispensable role of the microbiota.Measurement of short-chain fatty acids (SCFAs) further revealed a significant increase in the microbial metabolite butyrate following EMS treatment.Subsequent supplementation with sodium butyrate mimicked the therapeutic effects of EMS, ameliorating joint inflammation and cartilage damage.Mechanistically, butyrate enhanced the expression of intestinal tight junction proteins (ZO-1 and occludin), thereby restoring intestinal barrier integrity.Collectively, our results demonstrate that EMS exerts its anti-arthritic effects by modulating the gut microbiota-butyrate-intestinal barrier axis, highlighting the critical value of microbial metabolites in RA treatment.This study provides novel insights into the mechanism of EMS and suggests the therapeutic potential of butyrate for RA.

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• [18F]FDG-PET and [18F]MPPF-PET are brain biomarkers for the creatine transporter Slc6a8 loss of function mutation

  Scientific Reports · 2025-03-01 · 2 citations

  articleOpen access

  Abstract Pathogenic variants in the creatine transporter gene SLC6A8 , reported to represent 2% of all intellectual disabilities in males, result in a spectrum of behavioral abnormalities including developmental delay, intellectual disability, and deficit in speech. While at present there are no effective treatments available, preclinical development and testing of gene therapy and other approaches to increase brain creatine are being actively pursued. In studying a mouse model of the disorder, [ 18 F]fluorodeoxyglucose ([ 18 F]FDG)-based positron emission tomography (PET)/computed tomography (CT) was performed to assess brain glucose metabolism in wild type and creatine transporter mutant mice ( Slc6a8 -/y ). The findings demonstrate marked differences in glucose metabolism in the brains of wild type and Slc6a8 -/y mice. In conducting behavioral phenotyping studies, notable abnormalities in behavior in the murine model led to additional studies in serotonin-mediated activity. Serotonergic signaling differences were detected between wild type and Slc6a8 -/y mice using 4-(2′-methoxyphenyl)-1-[2′-( N -2″-pyridinyl)- p -[ 18 F]fluorobenzamido]ethylpiperazine ([ 18 F]MPPF). These data demonstrate that [ 18 F]FDG-PET and [ 18 F]-MPPF-PET may serve as appropriate and sensitive biomarkers that could be used to assess the efficacy of not only new approaches in treating mutations of the creatine transporter SLC6A8 and their effectiveness in normalizing brain metabolism but also in enhancing our understanding of the mechanism of brain dysfunction that occurs in this complex brain disorder.

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• Preclinical evaluation of high-resolution CT, 18F-FDG, and 18F-NaF PET imaging for longitudinal monitoring of atherosclerosis

  European Journal of Nuclear Medicine and Molecular Imaging · 2025-04-27 · 3 citations

  articleOpen access

  Abstract Rationale Detection of atherosclerosis is essential to the management and prevention of life-threatening cardiovascular events. Although non-invasive imaging modalities, such as 18 F-sodium fluoride ( 18 F-NaF), 18 F-fluorodeoxyglucose ( 18 F-FDG) PET, and CT, visualize distinct hallmarks of atherosclerosis, there has yet to be a singular multi-cohort interrogation of their strengths and limitations. Thus, we focused on identifying the optimal approach for visualizing atherosclerosis at different stages of disease progression. Methods In this study, 6-week-old, male, ApoE deficient mice ( Apoe −/− ) were placed on a high cholesterol diet for 12–20 weeks to induce calcific atherosclerotic disease. Age-matched, male, wildtype (WT) C57BL/6 mice fed with regular chow served as the control group. Mice were imaged at 12, 15, 18, and 20 weeks after starting their respective diets. To follow the progression of calcified atherosclerotic lesions, at each time point, in vivo , 18 F-NaF microPET/CT images were acquired 1 h and 3 h post tracer i.v. injection. In a separate cohort, in vivo 18 F-FDG PET/CT images were acquired at 3 and 5 h post tracer i.v. injection to follow inflammation as a result of progressive atherosclerotic lesion formation. High-resolution microCT images were acquired for all mice to visualize aorta calcification. After each imaging session, a subset ( n = 3) was euthanized from each group and histological analysis of the aorta was performed to confirm disease progression. Results In this comparative study, within the same cohort, 18 F-NaF PET detected atherosclerotic calcification earlier than microCT. At both 1 and 3 h post-injection (p.i.), calcified lesions were clearly detected by 18 F-NaF with a six-fold higher signal in Apoe -/- compared to WT mice. Interestingly, 18 F-NaF signal peaked at week 18, whereas aortic CT signal progressively increased with a 13-, 16-, and 29-fold at 15, 18, and 20 weeks, respectively. 18 F-FDG arortic accumulation at weeks 12 and 15, were significantly greater in Apoe −/− mice than WT control when images were acquired at 5 h but not at 3 h p.i.. In contrast to histological analysis, at ≥ 16 weeks where inflammation is significantly elevated, 18 F-FDG was equivalent in Apoe −/− and WT control mice and significantly reduced with disease progression. Conclusions Our results show that 18 F-NaF PET and 18 F-FDG PET are sensitive imaging modalities for the early detection of atherosclerotic lesions. However, both 18 F-NaF PET and high-resolution microCT prove to be effective methods for monitoring late-stage and progressive disease.

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Frequent coauthors

• Jason T. Lee

  42 shared

• Kirstin A. Zettlitz

  Beckman Research Institute

  35 shared

• Anna M. Wu

  35 shared

• Felix B. Salazar

  32 shared

• Mikayla Tamboline

  31 shared

• Oluwatayo Ikotun

  29 shared

• Tove Olafsen

  Beckman Research Institute

  26 shared

• Ann M. Chan

  26 shared

Education

• Ph.D., Pharmacology and Pharmaceutical Sciences

  University of Southern California

  2013

• B.S., Biological Sciences

  Peking University

  2007