About

Yury Miller is a Professor of Medicine at UC San Diego, with educational background from Russian State Medical University in Moscow, where he earned his MD in 1984 and PhD in 1990 in Biophysics. His research program focuses on the role of lipid metabolism and oxidation in fundamental biological processes and the development of human disease. His laboratory has made significant contributions by discovering the function of oxidized lipoproteins in activating toll-like receptors (TLRs), thereby connecting lipoprotein metabolism with inflammation in atherosclerosis. He pioneered the use of zebrafish models to study vascular lipid accumulation and inflammation, creating transgenic zebrafish lines with lipid abnormalities and genetic reporters for oxidized lipids. His work has led to discoveries regarding the functions of lipid and cholesterol metabolism in regulating vascular and neuroinflammation, neuropathic pain, and angiogenesis. Dr. Miller's research has been supported by multiple NIH grants, and he has contributed extensively to the understanding of immune mechanisms in atherosclerosis, neuroinflammation, and related fields.

Research topics

• Biology
• Medicine
• Chemistry
• Immunology
• Genetics
• Cell biology
• Endocrinology
• Virology
• Biochemistry
• Bioinformatics
• Pathology
• Internal medicine
• Pharmacology
• Neuroscience

Selected publications

• Increased atherosclerosis and expression of inflammarafts in macrophage foam cells in AIBP-deficient mice.

  Scientific Reports · 2026-02-07

  articleOpen accessSenior author

  Abstract Atherosclerotic lesions comprise different populations of macrophages, including lipid-laden macrophage foam cells and non-foamy, inflammatory macrophages, which play distinct roles in disease progression. Non-foamy macrophages express higher levels of inflammarafts – enlarged, cholesterol-rich lipid rafts hosting assemblies of inflammatory receptors – compared to foam cells in atherosclerotic lesions of Ldlr −/− mice. Apolipoprotein A-I binding protein (AIBP) has been shown to control lipid raft dynamics. This study investigated the effect of systemic AIBP deficiency on inflammaraft expression in foam cells and non-foamy macrophages in atherosclerotic lesions of hypercholesterolemic mice. A larger number of foam cells, with increased neutral lipid accumulation, populated atherosclerotic lesions in Apoa1bp −/− Ldlr −/− mice compared to Ldlr −/− mice. Importantly, AIBP-deficient foam cells expressed higher levels of TLR4 dimers and lipid rafts (markers of inflammarafts) than control mice, accompanied by larger atherosclerotic lesions and larger necrotic cores compared to Ldlr −/− mice. In a model of foam cells, Apoa1bp −/− bone marrow-derived macrophages incubated with oxidized LDL had increased expression of inflammation and atherosclerosis related genes. These results indicate that AIBP deficiency results in a phenotype shift in foam cells, characterized by increased lipid accumulation and increased expression of inflammarafts, and it correlates with the development of advanced atherosclerotic plaques.

  PublisherDOI

• Human Dorsal Root Ganglia Neuronal Cell Line to Study Nociceptive Signaling: A New Pipeline for Pain Therapy

  The FASEB Journal · 2026-02-03

  articleOpen access

  Nociceptive afferent neurons within the dorsal root ganglion (DRG) detect and relay painful peripheral stimuli, and the malfunctioning of this process leads to sustained pain states. Animal model studies have been invaluable for demonstrating the importance of the DRG nociceptor in pain sensation and the development of related analgesic targets. However, a human in vitro model of nociception is essential to confirming the relevance of preclinical findings for therapeutic drug development. We characterized the nociceptive properties of differentiated cells from the human DRG-derived immortalized cell line HD10.6 and developed their use into an in vitro model of human nociceptive signaling and therapy. Within differentiated HD10.6 cells, we confirmed the abundance and function of machinery linked with pain sensation, including key ion channels (TRPV1, NaV1.7) and afferent peptides (CGRP, Substance P), by immunofluorescence and calcium influx assays. Through whole-cell patch clamp, including current clamp and voltage clamp, we recorded the baseline electrophysiological parameters of differentiated HD10.6 cells. We further found that differentiated HD10.6 cells express the mu opioid receptor 1 protein, and that mu agonist DAMGO blocks depolarization-evoked calcium influx in a naloxone-reversible fashion. Importantly, excitation and peripheral sensitization were induced within HD10.6 cells in response to an inflammatory cocktail, mirroring nociceptors in a pain state during and after tissue damage or inflammation. HD10.6 cells were also cultured into dual-chambered microfluidic devices to mirror the physiological anatomy of the nociceptor. Within this system, genetic therapy adeno-associated-virus was successfully taken up by the peripheral terminals and transported to the soma.

  PublisherOA PDFDOI

• Age-associated chemokine receptor expression profiles in human peripheral blood monocyte subsets predict cardiovascular disease risk

  Frontiers in Immunology · 2026-02-23

  articleOpen access

  Background Aging is a major contributor to chronic inflammation and coronary artery disease (CAD), yet how age influences monocyte chemokine receptor expression in relation to disease severity remains incompletely defined. Methods and results We performed high-dimensional single-cell antibody sequencing (Ab-Seq) of peripheral blood mononuclear cells from 61 participants (ages 42–78 years) enrolled in the Coronary Assessment of Virginia (CAVA) cohort. Aging was associated with remodeling of monocyte populations, including a reduction in anti-inflammatory classical monocytes and an expansion of immature monocytes. Among younger individuals with severe CAD, intermediate monocyte subcluster iMo_HLA-DR int CCR2 low was increased, whereas anti-inflammatory classical monocyte cMo_CD33 hi CD163 hi CXCR4 + was reduced. In older individuals with progressive CAD, further reductions in CCR6 + and CXCR3 + classical monocytes were observed. Additional flow cytometry validation confirmed decreased CCR6-expressing classical monocytes in older individuals with high CAD burden. Independent of age, CXCR3-expressing intermediate monocytes were significantly increased in individuals with severe CAD. Transcriptomic analysis of CXCR3 + intermediate monocytes demonstrated increased expression of C1Q genes compared with CXCR3 low cells. Interestingly, chemokine receptor expression also correlated with lipid parameters in older individuals where CCR6 expression on intermediate monocytes positively associated with HDL cholesterol and increased with CAD severity, whereas CXCR3 expression on classical monocytes declined with advancing CAD. Conclusions Aging is associated with distinct changes in monocyte chemokine receptor expression that relate to CAD severity. These findings identify age- and disease-associated monocyte immune features that may contribute to CAD progression.

  PublisherOA PDFDOI

• Progressive Loss of Astrocytic AIBP Expression during Alzheimer’s Disease Pathology

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-03

  preprintOpen accessSenior authorCorresponding

  Abstract Astrocytes and microglia play crucial roles in mediating neuroinflammation during Alzheimer’s disease (AD) progression. ApoA-I binding protein (APOA1BP, also known as AIBP/NAXE) attenuates neuroinflammation by blocking amyloid β-induced TLR4 inflammaraft formation and oxidative stress. Apoa1bp knockout in APP/PS1 mice exacerbates microgliosis, increases amyloid plaque burden, neuronal cell loss, and reduces survival at 6 months. Although APOA1BP mRNA is ubiquitously expressed in humans, its cell-type-specific distribution in the brain remains unclear. To examine AIBP protein expression in the human brain, we performed immunohistochemistry on hippocampal sections from postmortem brain specimens from subjects aged 75-96 of both sexes. Using GFAP and IBA1 to label astrocytes and microglia, respectively, we found that AIBP protein was highly expressed in astrocytes, but not in microglia. Stratification of subjects by Braak stage (I-II, III-IV, V-VI) revealed a progressive decline in astrocytic AIBP expression with advancing AD pathology. Meta-analysis of RNA-seq profiling indicated enriched Apoa1bp expression in adult mouse astrocytes. Systemic Apoa1bp knockout in the APP/PS1 mouse exacerbated astrogliosis. These findings demonstrate that AIBP is predominantly expressed in astrocytes and its expression declines with AD progression, suggesting a potential role for AIBP in astrocyte-mediated neuroprotection and AD pathogenesis.

  PublisherOA PDFDOI

• Human dorsal root ganglia neuronal cell line to study nociceptive signaling: a new pipeline for pain therapy

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-28

  preprintOpen access

  Abstract Nociceptive afferent neurons within the dorsal root ganglion (DRG) detect and relay painful stimuli from the periphery to the brain, and the malfunctioning of this process leads to sustained pain states. Animal model studies have been invaluable for demonstrating the importance of the DRG nociceptor in pain sensation and the development of related analgesic targets. However, there are functional biological differences between human and animal model nociceptors. Therefore, a complementary in vitro model of human nociception is critical to confirming the relevance of preclinical findings for therapeutic drug development. We characterized the nociceptive properties of differentiated cells from the human DRG-derived immortalized cell line HD10.6. Within differentiated HD10.6 cells, we documented the abundance and localization of nociceptive machinery central to regulating excitability and linked with pain sensation including ion channels TRPV1 and NaV1.7 and afferent peptides CGRP and Substance P. Using calcium influx imaging assays, we confirmed the electrical functionality of TRPV1 and NaV1.7 in HD10.6 cells, and through whole-cell patch clamp, we found similar baseline electrophysiological parameters of HD10.6 cells to those previously observed in human patient DRGs. Further, we found that differentiated HD10.6 cells express the mu opioid receptor 1 protein, and DAMGO, a mu agonist, blocks depolarization-evoked calcium influx in a naloxone-reversible fashion. Importantly, using an inflammatory cocktail, excitation and peripheral sensitization are induced within HD10.6 cells, mirroring nociceptors in a pain state during or after tissue damage or inflammation. Finally, HD10.6 cells were also cultured into dual-chambered microfluidic devices to mirror the biological anatomy of the nociceptor. Within this system, we demonstrated the uptake of adeno-associated-virus (AAV) by the peripheral terminals and AAV transport to the soma. Altogether, we have developed the use of HD10.6 cells to create a system of human nociceptive signaling on a chip to study human nociceptor physiology and intervention. Perspective There are essential differences between human and animal model nociceptors. Here, we develop a physiological model of “nociceptive signaling on a chip” using human-derived nociceptors to ultimately enhance the translatability of preclinical afferent signaling research to the human patient.

  PublisherOA PDFDOI

• Virally-initiated pain states: phenotypes, mechanisms, and future directions

  Frontiers in Pain Research · 2025-01-28 · 1 citations

  articleOpen access

  The recent SARS-CoV-2 pandemic has underscored the significance of viral infections, affecting billions of lives and costing trillions of dollars globally. Even beyond SARS-CoV-2, common infections with viruses like influenza, HIV, and herpesviruses have profound impacts beyond their typical manifestations, often triggering acute and chronic pain syndromes that can be life-altering. These virally induced pain states can arise through direct viral replication within neurons, or indirectly, via immune responses to infection in both the contexts of afferent signaling in the dorsal root ganglion (DRG) or subsequent higher order integration in intracranial systems. Varicella-zoster virus (VZV), influenza virus, and SARS-CoV-2 each provide a unique lens through which to examine the interplay between viral activity and pain. This perspective paper is not meant to be an exhaustive review of virally-induced neuropathic pain states. It seeks to explore curated aspects of the complexities of these pain states, identify research gaps, and suggest solutions using nanoscale molecular understanding and psychoneuroimmunological and biopsychosocial frameworks. Each subheading is accompanied by a list of related issues for study which we think will lead to advances in our understanding of the vexing pain phenotype associated with viral infection.

  PublisherOA PDFDOI

• Chronic Pain Induced by Social Defeat Stress in Juvenile Mice Depends on TLR4

  Cells · 2025-02-27 · 2 citations

  articleOpen access

  A significant portion of adolescents suffer from mental illnesses and persistent pain due to repeated stress. The components of the nervous system that link stress and pain in early life remain unclear. Prior studies in adult mice implicated the innate immune system, specifically Toll-like receptors (TLRs), as critical for inducing long-term anxiety and pain-like behaviors in social defeat stress (SDS) models. In this work, we investigated the pain and anxiety behavioral phenotypes of wild-type and TLR4-deficient juvenile mice subjected to repeated SDS and evaluated the engagement of TLR4 by measuring dimerization in the spinal cord, dorsal root ganglia, and prefrontal cortex. Male juvenile (4-week-old) mice (C57BL/6J or Tlr4-/-) underwent six social defeat sessions with adult aggressor (CD1) mice. In WT mice, SDS promotes chronic mechanical allodynia and thermal hyperalgesia assessed via von Frey testing and the Hargreaves test, respectively. In parallel, the stressed WT mice exhibited transient anxiety-like behavior and long-lasting locomotor activity reduction in the open-field test. Tlr4-/--stressed animals were resistant to the induction of pain-like behavior but had a remnant of anxious behavior, spending less time in the center of the arena. In WT SDS, there were concordant robust increases in TLR4 dimerization in dorsal root ganglia macrophages and spinal cord microglia, indicating TLR4 activation. These results suggest that the chronic pain phenotype and locomotor impairment induced by SDS in juvenile mice depends on TLR4 engagement evidenced by dimerization in immune cells of the dorsal root ganglia and spinal cord.

  PublisherOA PDFDOI

• Restoring AIBP expression in the retina provides neuroprotection in glaucoma

  Molecular Therapy · 2025-05-09 · 8 citations

  articleOpen access
  PublisherOA PDFDOI

• Chronic Pain Induced by Social Defeat Stress in Juvenile Mice Depends on TLR4

  Preprints.org · 2025-01-22

  preprintOpen access

  A significant portion of adolescents suffer from mental illnesses and persistent pain due to repeated stress. It remains unclear which components of the nervous system are involved in the linkage between stress and pain at an early age. Prior studies in adult mice implicated the innate immune system, specifically Toll-like receptors (TLR), as critical for inducing long-term anxiety and pain-like behavior in social defeat stress (SDS) model. In this work, we investigated the pain and anxiety behavioral phenotypes of wild-type and TLR4-deficient juvenile mice subjected to repeated SDS and evaluated the engagement of TLR4 by measuring dimerization in the spinal cord, dorsal root ganglia, and prefrontal cortex. Male juvenile (4-week-old) mice (C57BL6/J or Tlr4-/-) underwent six social defeat sessions with adult CD1 aggressors. In WT mice SDS promotes chronic mechanical allodynia by von Frey testing and thermal hyperalgesia by Hargreaves test. In parallel, the stressed WT mice exhibited transient anxiety-like behavior and long-lasting locomotor activity reduction in the open-field test. Tlr4-/- stressed animals were resistant to the induction of pain-like behavior but had a remnant of anxious behavior, spending less time in the center of the arena. In WT SDS, there were concordant robust increases of TLR4 dimerization in dorsal root ganglia macrophages and spinal cord microglia, indicating activation. These results suggest that the chronic pain phenotype and locomotor impairment induced by SDS in juvenile mice depends on TLR4 engagement evidenced by dimerization in immune cells of the dorsal root ganglia and spinal cord.

  PublisherOA PDFDOI

• Amyloid β-Induced Inflammarafts in Alzheimer’s Disease

  International Journal of Molecular Sciences · 2025-05-10 · 5 citations

  reviewOpen accessSenior authorCorresponding

  The formation of amyloid beta (Aβ) plaques is a central process in the development of Alzheimer's disease (AD). Although its causative role or the effectiveness of therapeutic targeting is still debated, the key involvement of Aβ in the pathogenesis of neuroinflammation and neurodegeneration in AD is broadly accepted. In this review, we emphasize the role of lipid rafts, both in APP cleavage producing Aβ in neurons and in mediating Aβ inflammatory signaling in microglia. We introduce the term inflammarafts to characterize the Aβ-driven formation of enlarged, cholesterol-rich lipid rafts in activated microglia, which support protein-protein and lipid-protein interactions of inflammatory receptors. Examples reviewed include toll-like receptors (TLR2, TLR4), scavenger receptors (CD36, RAGE), and TREM2. The downstream pathways lead to the production of cytokines and reactive oxygen species, intensifying neuroinflammation and resulting in neuronal injury and cognitive decline. We further summarize emerging therapeutic strategies and emphasize the utility of apolipoprotein A-I binding protein (AIBP) in selective targeting of inflammarafts and attenuation of microglia-driven inflammation. Unlike the targeting of a single inflammatory receptor or a secretase, selective disruption of inflammarafts and preservation of physiological lipid rafts offer a novel approach to targeting multiple components and processes that contribute to neuroinflammation in AD.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01HL124174

  NIH · $1.0M · 2019

• Reversal of preexisting neuropathic pain by spinal delivery of AIBP

  NIH · $377k · 2018–2022

• Role of TLR4-lipid rafts in nociception

  NIH · $2.3M · 2024–2028

• Immune Cell Interactions in Atherosclerosis

  NIH · $36.5M · 2017–2027

• NIH Grant P01HL055798

  NIH · $26.3M · 2017

Frequent coauthors

• Longhou Fang

  Houston Methodist

  105 shared

• John Y.‐J. Shyy

  University of California, San Diego

  65 shared

• Shing‐Jong Lin

  National Yang Ming Chiao Tung University

  64 shared

• Greg G. Geary

  Houston Methodist

  64 shared

• Shu Chien

  La Jolla Bioengineering Institute

  64 shared

• Po‐Hsun Huang

  Taipei Veterans General Hospital

  64 shared

• McKenna J. Geary

  University of California, San Diego

  64 shared

• Marcy Martin

  University of Zurich

  64 shared