About

Yingxian Pan is a Professor in the Department of Anesthesiology at Rutgers New Jersey Medical School. His research focuses on the molecular and cellular mechanisms of mu opioid receptor actions, with an emphasis on understanding how alternative pre-mRNA splicing of the OPRM1 gene generates multiple receptor isoforms that mediate the complex actions of opioids. His work aims to translate basic scientific findings into the development of novel opioid analgesics that provide potent pain relief without the side effects typically associated with traditional opioids. Dr. Pan's research utilizes multidisciplinary approaches, including molecular biology, biochemistry, pharmacology, behavioral studies, and gene targeting animal models, to investigate mechanisms underlying opioid tolerance, respiratory depression, reward, and biased signaling at mu opioid receptor splice variants. His contributions have significantly advanced the understanding of opioid receptor diversity and its implications for pain management and addiction treatment.

Research topics

• Pharmacology
• Biology
• Biochemistry
• Chemistry
• Genetics
• Stereochemistry
• Neuroscience
• Internal medicine
• Psychology
• Medicine

Selected publications

• Differential impacts of exon 1–associated and exon 11–associated variants of the rat mu opioid receptor gene, Oprm1, on buprenorphine- and morphine-induced analgesia and respiratory depression in male rats

  Molecular Pharmacology · 2026-02-17

  articleSenior author
  PublisherDOI

• Switchable Nanophotosensitizers as Pyroptosis Inducers for Targeted Boosting of Antitumor Photoimmunotherapy

  Biomacromolecules · 2025-04-08 · 1 citations

  articleCorresponding

  Photodynamic therapy (PDT) has emerged as a promising modality for cancer treatment, but its clinical application is constrained by unexpected phototoxicity arising from nonspecific photosensitizer activation and their "always-on" nature. Herein, we developed a switchable nanophotosensitizer, poly(cation-π) nanoparticles (NP), which achieves supramolecular assembly through cation-π interactions. By coupling choline cationic moieties with aromatic photosensitizers (ZnPc), the polymer facilitates self-assembly driven by cation-π interactions for NP engineering. Surprisingly, the photoactivity of ZnPc was completely quenched upon complexation via cation-π interactions, thereby significantly avoiding skin phototoxicity. Upon targeting tumor cells, NP undergoes a GSH-responsive degradation process that weakens cation-π interactions, leading to spontaneous restoration of photoactivity and amplifying tumor immunogenic pyroptosis. In vivo studies demonstrated that NP achieved a high tumor inhibition rate of 84% while effectively avoiding skin phototoxicity. This work provides a novel perspective for enhancing the safety and efficacy of PDT-based tumor treatment.

  PublisherDOI

• Exploring immunological alterations of B cells in peripheral immunity via single-cell RNA sequencing: insights into primary membranous nephropathy

  Frontiers in Immunology · 2025-08-19 · 1 citations

  articleOpen access

  Background: Primary Membranous Nephropathy (PMN) is characterized by dysregulated immune responses, with B cells playing critical roles in disease pathogenesis. However, the immunopathogenic mechanisms underlying B cell involvement in PMN remain elusive. Methods: We employed single-cell RNA sequencing on peripheral blood mononuclear cell samples (PBMC) obtained from 6 patients with PMN and 3 healthy controls (NC) to explore the transformation of B cells and their interaction with immune cells. Results: Compared with NC, the most significant alterations were in plasma cells and regulatory B (Breg) cells in PMN patients. Within plasma cells, Subcluster 0 was increased in PMN patients and exhibited enhanced autoimmunity. Breg subset B10 cells were elevated in PMN patients and displayed increased immune regulatory capacity, marked by enhanced cytokine and interleukin-10 production. B cell activating factor (BAFF) and galectin-9, which were secreted by CD14 monocyte, as potential regulators of plasma and Breg cells activity. Additionally, serum galectin-9 levels increased in PMN patients and showed a correlation with proteinuria and renal function in PMN. Conclusions: We reveal novel insights into the heterogeneity and functional diversity of B cells in patients with PMN. And revealed distinct roles for subgroup 0 plasma cells and B10 Breg cells in the pathogenesis of PMN. Furthermore, targeting B cells, such as galectin-9, presents promising opportunities for modulating the immune response in patients with PMN.

  PublisherOA PDFDOI

• Structural and Functional Characterization of a Novel 4,5-Dihydroxyphthalate Decarboxylase for Protocatechuic Acid Biosynthesis

  Journal of Agricultural and Food Chemistry · 2025-11-12

  article1st author

  Phthalate esters (PAEs) constitute a widespread class of xenobiotic contaminants characterized by environmental persistence and ecological recalcitrance. Under aerobic conditions, PAE mineralization proceeds via 4,5-dihydroxyphthalate (4,5-DHP) as a key metabolic intermediate, which undergoes stereospecific decarboxylation to protocatechuate (PCA), a versatile pharmacophore with broad therapeutic potential. Here, we elucidate the molecular architecture and catalytic determinants of a previously uncharacterized 4,5-DHP decarboxylase (DhpD) isolated from ultramicrobacteria. Enzymatic assays revealed that PAE-UM2851 exhibits peak activity at pH 7.5 and 45 °C, with a Km of 911.5 μM. Functional characterization confirmed that PAE-UM2851 catalyzes the decarboxylation of 4,5-DHP to PCA, supported by FTIR spectral evidence showing reduced – CO (1640 cm–1) and – OH (3450 cm–1) vibrational modes. Structure–function analysis identified five evolutionarily conserved residues (Ser57, Arg84, Thr115, Lys150, and His223) essential for regulating regioselective decarboxylation. This study not only clarifies the catalytic mechanism of DhpD but also outlines a potential biosynthetic route for PCA.

  PublisherDOI

• Transcriptomic profile of Lutraria sieboldii larvae: Insights into the molecular mechanisms of attachment and metamorphosis

  Comparative Biochemistry and Physiology Part D Genomics and Proteomics · 2025-06-19

  articleCorresponding
  PublisherDOI

• Synthesis and Pharmacology of a Morphinan-Derived Dual Mu–Kappa Opioid Receptor Agonist Analgesic

  ACS Chemical Neuroscience · 2025-06-26 · 2 citations

  article

  We present the synthesis and pharmacological characterization of 3′-iodobenzoylamido epoxymorphinans, with a saturated ring C and devoid of 14-OH, based on a dihydronormorphine backbone with various N-17 alkyl substitutions. All synthesized compounds were characterized pharmacologically in radioligand binding assays, [35S] GTPγS functional assays, and for antinociception in mice. Among these analogues, MP1202, a pan-opioid receptor analogue, was characterized further in β-arrestin1/2 studies, G-protein recruitment and Gα-subtype profiling, as well as by evaluation of opioid-mediated effects in mice. MP1202 exhibits potent antinociceptive effects in mice without causing typical opioid side effects, such as respiratory depression and physical dependence. However, it displays conditioned place preference and aversion behaviors similar to those of classical mu and kappa agonists.

  PublisherDOI

• Efficacy of different modes of exercise-based cardiac rehabilitation delivery for patients with heart failure: a systematic review and network meta-analysis

  Cardiovascular Diagnosis and Therapy · 2025-06-01 · 2 citations

  reviewOpen access

  Background: Cardiac rehabilitation (CR) has been shown to be an effective treatment for patients with heart failure (HF). However, the effect of different modes of CR delivery on HF remains unclear. The purpose of this study is to perform a large-scale pairwise and network meta-analysis (NMA) on the impact of various exercise types on patients with HF using multiple indicators. Methods: , six-minute walk test (6MWT), maximum workload, left ventricular ejection fraction (LVEF), maximum heart rate (MHR), and Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores. All relevant studies reported well-defined or accessible exposures and presented clear data on any one or more of the six items above before and after exercise rehabilitation. Results: , was HIIT (SUCRA: 90.8%), strength training (ST) (74.7%), AT (64.4%), combined training (CT) (41.7%) and inspiratory muscle training (IMT) (18.3%). The order of effectiveness for LVEF based on SCURA values was HIIT (90.5%), AT (77.8%), CT (50.3%), ST (49.9%) and IMT (7.7%). Conclusions: Various types of exercise, especially HIIT, can improve QoL, cardiac function, LVEF, and exercise tolerance in patients with HF. The results of this analysis should inform future exercise guideline personalized recommendations and prescriptions for HF patients.

  PublisherDOI

• Elevating levels of the endocannabinoid 2-arachidonoylglycerol blunts opioid reward but not analgesia

  Science Advances · 2024-11-29 · 11 citations

  articleOpen access

  Converging findings have established that the endocannabinoid (eCB) system serves as a possible target for the development of new treatments as a complement to opioid-based treatments. Here, we show in male and female mice that enhancing levels of the eCB, 2-arachidonoylglycerol (2-AG), through pharmacological inhibition of its catabolic enzyme, monoacylglycerol lipase (MAGL), either systemically or in the ventral tegmental area (VTA) with JZL184, leads to a substantial attenuation of the rewarding effects of opioids in mice using conditioned place preference and self-administration paradigms, without altering their analgesic properties. These effects are driven by cannabinoid receptor 1 (CB1R) within the VTA, as VTA CB1R conditional knockout counteracts JZL184's effects. Using fiber photometry with fluorescent sensors for calcium and dopamine (DA), we find that enhancing 2-AG levels diminishes opioid reward-related nucleus accumbens (NAc) activity and DA neurotransmission. Together, these findings reveal that 2-AG diminishes the rewarding properties of opioids and provides a potential adjunctive therapeutic strategy for opioid-related analgesic treatments.

  PublisherDOI

• Targeting Exon 7-associated 7TM C-Terminal Variants of the Mu Opioid Receptor Gene for Mitigating Adverse Effects of Mu Opioids Without Altering Analgesia in Pain Management

  Journal of Pharmacology and Experimental Therapeutics · 2024-05-13

  article1st authorCorresponding
  PublisherDOI

• Associations of Digital Ulcers in Patients with Systemic Sclerosis: An 8-Year Retrospective Study

  Dermatology · 2024-01-01

  articleSenior authorCorresponding

  INTRODUCTION: This study aimed to investigate the associations of digital ulcers (DUs) in patients with systemic sclerosis (SSc). METHODS: This retrospective study investigated the demographic characteristics, specific autoantibodies, organ involvement, and laboratory tests in patients with SSc from our hospital. RESULTS: This study enrolled 144 patients with SSc. The DU+ group consisted of 15 (10.4%) patients. Patients with SSc having DUs have longer disease duration, higher fibrinogen, higher fibrin degradation product, and lower cholesterol. None of the patients used cholesterol-lowering drugs before onset of DUs. The study also demonstrated a higher prevalence of anti-dsDNA and anti-histone antibodies in patients with SSc with DUs. Anti-dsDNA antibody is a specific antibody for SLE with a specificity of 96-99%. A total of 86.1% (124/144) of patients suffered from diffuse cutaneous SSc, and 28.5% (41/144) of patients suffered from overlap syndrome. CONCLUSION: Our study indicated that patients with SSc with fibrinogen of >2.895 g/L (p = 0.043) and cholesterol of <3.340 mmol/L (p = 0.036), which is equal to 129.258 mg/dL, are at high risk of developing DUs.

  PublisherDOI

Recent grants

• Arylepoxamides: A new class of potent, safer analgesics

  NIH · $6.8M · 2020–2021

• Alternative pre-mRNA splicing of mu opioid receptor gene and mu opioid actions

  NIH · $1.9M · 2020–2023

• Exploring function of mu opioid receptor splice variants in rat by gene targeting

  NIH · $471k · 2016–2019

• NIH Grant R01DA013997

  NIH · $3.3M · 2014

• Pharmacology of opioid actions in vivo

  NIH · $6.9M · 2020–2023

Frequent coauthors

• Gavril W. Pasternak

  Kettering University

  96 shared

• Jin Xu

  Rutgers, The State University of New Jersey

  62 shared

• Susruta Majumdar

  Washington University in St. Louis

  44 shared

• Yimin Li

  Guangzhou Medical University

  42 shared

• Grace C. Rossi

  University of Washington

  27 shared

• Tao Che

  Washington University in St. Louis

  23 shared

• Ling Sang

  22 shared

• Xiaoqing Liu

  State Key Laboratory of Respiratory Disease

  20 shared

Education

• M.D.

  Shanghai University of Traditional Chinese Medicine

  1982

• M.S., Biochemistry

  Shanghai University of Traditional Chinese Medicine

  1986

• Ph.D., Physiology & Biophysics

  University of Cincinnati

  1993