About

Jiyuan "Jane" Yang is a faculty member in the College of Pharmacy at the University of Utah, associated with the Department of Molecular Pharmaceutics. The page does not provide specific details about her research focus, background, or key contributions. Therefore, no further biographical information is available from the provided content.

Research topics

• Medicine
• Biology
• Immunology
• Biochemistry
• Cancer research
• Chemistry
• Pharmacology
• Molecular biology
• Cell biology
• Materials science
• Computational biology
• Internal medicine
• Nanotechnology
• Organic chemistry
• Combinatorial chemistry

Selected publications

• CD38-targeted antibody-polymer drug conjugates for enhanced treatment of multiple myeloma

  Biomaterials · 2025-06-04 · 8 citations

  articleOpen accessSenior authorCorresponding

  Multiple myeloma (MM) remains a formidable disease, especially in relapsed or refractory cases when there are limited treatment options. In this study, we introduce two polymer-antibody drug conjugates (pADCs), ISA-P-EPI (U6244-021) and DARA-P-EPI (U6244-031), which contain semitelechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-epirubicin (EPI) conjugate attached to CD38-targeting antibodies Isatuximab (ISA) and Daratumumab (DARA). These pADCs enhance therapeutic efficacy by combining the specificity of ISA and DARA with the cytotoxic potency of EPI while preserving antibody function. The EPI is linked to the HPMA polymer backbone via a tetrapeptide spacer cleavable by lysosomal enzymes, enabling drug release upon endocytosis within tumor cells. This design achieves a higher drug-to-antibody ratio than conventional ADCs for safer delivery of drug payload. In vitro studies demonstrate efficient binding, internalization, and cytotoxic efficacy of these pADCs in MM cell lines. Mechanistic investigations revealed significant therapeutic effects, including cell cycle arrest, immunogenic cell death, and preserved antibody-dependent cellular cytotoxicity (ADCC). In addition, pADCs were effective in 5 out of 8 primary samples, with their efficacy closely correlating with CD38 surface expression levels. To enhance therapeutic outcomes, we employed panobinostat to upregulate CD38 expression, which further improved pADC efficacy. In a preclinical NRG mouse model inoculated with MM.1S-luc cells, pADC treatment significantly delayed tumor progression and prolonged survival, with all treated mice remaining alive at the 100-day endpoint. These findings underscore the potential of CD38-targeted pADCs as a novel approach to combining chemotherapy with immunotherapy for MM treatment, warranting further investigation into their optimization and clinical application.

  PublisherDOI

• Two-component T-cell immunotherapy enables antigen pre-targeting to reduce cytokine release without forfeiting efficacy

  Nanomedicine Nanotechnology Biology and Medicine · 2025-04-30 · 2 citations

  articleOpen access

  Contemporary T-cell immunotherapies, despite impressive targeting precision, are hindered by aberrant cytokine release and restrictive targeting stoichiometry. We introduce a two-component T-cell immunotherapy targeting B-cell malignancies: Multi-Antigen T-Cell Hybridizers (MATCH). This split antibody technology differs from current therapies by separating cancer cell-targeting components from T cell-engaging components. We demonstrate that this two-component structure facilitates tunable T-cell activation. αCD19 and αCD20 MATCH, administered in two steps, are both compared to the clinical standard bispecific antibody, blinatumomab. In vitro two-dimensional dose analysis and cytokine release data indicate MATCH improves cancer clearance with reduced cytokine release. Cytolytic mechanisms of action are evaluated. αCD20 MATCH anti-cancer efficacy is assayed using a human lymphoma murine model. Decreasing T-cell engager dose 10-fold yields comparable efficacy to non-reduced doses. Ultimately, this split-antibody paradigm may enhance antigen targeting while reducing cytokine release, with such safety and efficacy advantages augmented by the future possibility of multi-antigen targeting with MATCH.

  PublisherDOI

• Preparation of K-carrageenan /polylactic acid nanofiber membranes encapsulating Vitamin C/ Hydroxypropyl-beta-cyclodextrin inclusion complexes by electrostatic spinning for blueberry preservation

  Food Bioscience · 2025-05-20 · 10 citations

  article
  PublisherDOI

• DDEL-09. Therapeutic activation of primary CNS lymphoma immunity by BBB-penetrant c-Myc targeted biopolymer, and anti-PD-1: artificial intelligence guided pathway insights

  Neuro-Oncology · 2025-11-01

  articleOpen accessSenior author

  Abstract Primary central nervous system lymphoma (PCNSL) is a lethal cancer with poor survival, especially in its recurrent form. This is mainly due to low penetrance of therapeutic agents across the blood brain barrier (BBB). We created a novel nano immunodrug (nanodrug) that can cross the BBB and deliver anti-cancer agents directly to the tumor. The RNA therapeutics based on N-(2-hydroxypropyl)methacrylamide copolymer nanoplatform that was designed to block lymphoma’s cell c-Myc protein synthesis and to ensure brain tumor targeting and BBB crossing. Inhibiting of c-Myc protein synthesis played a dual role as anti-tumor proliferative factor and immune stimulator. Angiopep-2 peptide is conjugated to the nano platform to provide BBB crossing and brain lymphoma cell targeting via LRP-1 receptor. The nanodrug also contains H6 (6 histidines for endosome escape) to release into lymphoma cell cytoplasm. We tested the nanodrug in a A20 intracranial brain lymphoma mouse model alone, and in combination with anti-PD-1 antibody. Treatment with nanodrug resulted in a significant survival advantage compared to control. Survival was significantly enhanced when the nanodrug was co-injected with anti-PD-1. Spectral flow cytometry and RNA-seq analysis of treated tumors showed robust activation of tumor-infiltrating T lymphocytes with enhanced interferon γ signaling and polarization to M1-type macrophages. Artificial Intelligence-assisted analysis of gene expression data from RNA-seq revealed novel immune pathways, molecular targets, and suggested effective multifunctional drugs. Overall, we created a novel nano therapeutic drug delivery system that inhibits tumor c-Myc protein to treat PCNSL. When used in conjunction with anti-PD-1 checkpoint inhibitor, the treatment results in enhanced survival of tumor bearing animals by activating both adaptive and immune responses. SUPPORT NIH grants: R01 CA246716, R01 CA206220, R01 CA209921, R01 CA284247

  PublisherOA PDFDOI

• Immune cell tumor engagers (SITE) via morpholino-guided self-assembly for precision immunotherapy of multiple myeloma

  Blood · 2025-11-03

  article

  Abstract Introduction: Bispecific T cell engagers have shown significant clinical efficacy and are currently FDA approved for the treatment of relapsed and refractory multiple myeloma (RRMM). However, challenges remain, including targeting flexibility, immune-related toxicity, and durability of response. To overcome these limitations, we developed Self-Assembled Immune Cell-Tumor Engagers (SITE), a two-component system that targets both immune cell and MM cell surface antigens; each component is tagged with a complementary morpholino oligonucleotide (M1 or M2). Upon administration, these components hybridize in situ via M1-M2 pairing to form bispecific complexes to redirect immune cells to MM cells. Utilization of this pre-targeting approach enables the sequential engagement of immune cells, including T cells, NK cells, and macrophages. Additionally, by simultaneously targeting of multiple antigens (i.e. BCMA, GPRC5D and CD38), this strategy minimizes the risk of antigen loss and immune escape. Herein, we report the efficacy of SITE across multiple models, including in vitro cell lines, ex vivo patient-derived samples, and in vivo mouse models, demonstrating its potential as an innovative, cost-effective platform for orchestrating a coordinated and robust anti-tumor immune response. Methods: Anti-MM antibodies were digested enzymatically to F(ab')2 fragments, further reduced with tris(2-carboxyethyl)phosphine to generate Fab'MM-thiols. A pair of 25 bp M1/M2 was customized from Genetools. Following 3'-end maleimido modification, a panel of Fab'MM-M1 targeting BCMA, GPRC5D and CD38 was obtained. Similarly, α-hCD3 and α-hCD314 were used to generate immune cell targeting Fab'immune-M2. Stability of M1-M2 hybrids was assessed using circular dichroism (CD) spectroscopy in PBS, and size-exclusion chromatography (SEC) following incubation in mouse serum. Primary human T cells and NK cells were isolated from healthy donor blood. In vitro cytotoxicity and immune activation of SITE were assessed by flow cytometry on MM.1S and RPMI-8226 cells. To assess therapeutic efficacy, both patient-derived bone marrow mononuclear cells and a preclinical NRG mouse model were utilized. Mice were sub-lethally irradiated and i.v. injected with 3×106 MM.1S-Luc cells. Human T cells (9×106,3×106, or1×106) were administered to study the influence of T cells. Different dosing regimens (premix vs. consecutive) of T cell-specific SITE constructs (Fab'BCMA-M1/Fab'CD3-M2) were evaluated and compared with conventional teclistamab treatment. Cytokine production (IL-2, IFN-γ, TNF-α) was analyzed, and immune cell subsets were profiled by flow cytometry. Results: Conjugates Fab'MM-M1 and Fab'immune-M2 were successfully synthesized; hybridization of Fab'MM-M1/Fab'immune-M2 upon 1:1 mixing was confirmed by a shift in elution profiles in SEC. Complexes remained stable in 10% mouse serum for over 24 h. CD spectra showed a positive peak at 260 nm and a negative minimum at 210 nm, indicating formation of A-form double helices under physiological conditions. In vitro, SITE constructs successfully engaged T cells and NK cells, triggering potent cytotoxicity towards MM.1S and RPMI-8226 cells. Flow cytometry demonstrated increased expression of activation markers and induction of apoptosis in target cells. Ex vivo studies using patient-derived samples confirmed significant clearance of MM cells by patient's own T cells. In vivo, NRG mice bearing MM.1S-Luc and treated with SITE-T cell therapy extended survival and inhibited tumor growth compared to teclistamab-treated groups. Flow cytometric analysis of bone marrow confirmed a marked reduction in MM.1S cell populations in SITE-treated mice. T cell-related toxicity was found to be associated with injected T-cell numbers: reducing the dose from 9×106 to 3×106 or lower, no body weight loss occurred, highlighting the advantageous flexibility of two-component SITE. Overall, SITE demonstrated a superior anti-tumor effect compared to teclistamab, highlighting its potent efficacy in controlling MM progression in vivo. Conclusion: The SITE platform represents a promising advance in immunotherapy for MM, offering a versatile, potent, and modular approach to address the disease's complex antigenic landscape. By enabling multi-antigen targeting and the orchestration of diverse immune effectors, the platform effectively overcomes challenges such as antigenic heterogeneity, immune escape, and cytokine release syndrome.

  PublisherDOI

• Polymer-based chemo-immunotherapy: Combining immunogenic cell death induction and PD-L1 blockade enhances antitumor immunity in melanoma

  Journal of Controlled Release · 2025-09-02 · 3 citations

  articleOpen accessSenior authorCorresponding

  Melanoma remains a challenging malignancy despite the significant outcomes achieved with immune checkpoint inhibitor (ICI) monotherapy. Here, we investigated a polymer-based chemo-immunotherapy strategy combining KT-1, a backbone-degradable N -(2-hydroxypropyl)methacrylamide (HPMA) copolymer–epirubicin conjugate that induces immunogenic cell death (ICD), with MPPA, a multivalent HPMA copolymer–peptide antagonist of PD-L1 (PPA: (NYSKPTDRQYHF). In B16F10 melanoma, a 3-day dosing schedule significantly outperformed 7-day dosing. KT-1 monotherapy induced CD8 + T cell–mediated immunity through increased infiltration and upregulation of effector genes (Prf1, Gzmk, Eomes, Xcl1, Cxcl10), with depletion studies confirming CD8 + T cell dependence. Concurrent KT-1 + MPPA administration proved superior to sequential dosing. Single-cell RNA sequencing revealed that KT-1 promoted dendritic cell maturation and CD8 + T cell activation, while MPPA selectively reversed KT-1–induced PD-L1 upregulation on tumor cells. The combination enhanced dendritic cell activation, CD8 + T cell cytotoxicity, and reduced regulatory T cell immunosuppression. Importantly, MPPA did not induce autoimmune diabetes in NOD mice, in contrast to conventional anti–PD-L1 antibodies, and showed no observed immune-related adverse effects highlighting the safety. These findings support HPMA copolymer-based chemo-immunotherapy as a safer, effective alternative to traditional ICI regimens for treating immune-excluded tumors.

  PublisherDOI

• Chronic Ethanol Drinking Alters Medial Prefrontal Cortex and Nucleus Accumbens Astrocyte Translatome and Extracellular Matrix Glycosaminoglycans

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-02

  preprintOpen access

  Alcohol Use Disorder is a leading preventable cause of morbidity and mortality, yet knowledge of mechanisms driving ethanol-related neuroplasticity remains incomplete. While research has traditionally focused on neuronal signaling, emerging evidence implicates astrocytes in addiction-related adaptations. Here, we investigated the astrocyte-specific molecular consequences of chronic ethanol consumption in the prefrontal cortex and nucleus accumbens, two brain regions critical for executive control and reward processing. Using Translating Ribosome Affinity Purification RNA-seq and bulk RNA-seq in Aldh1l1-EGFP/Rpl10a mice, expressing an EGFP tag on astrocyte ribosomes, we identified hundreds of differentially translated astrocytic genes following chronic continuous two-bottle choice ethanol drinking. Sex-specific analyses revealed greater astrocytic changes in the female PFC and male NAc. Pathway enrichment highlighted extracellular matrix remodeling, synaptic signaling, mitochondrial function, and immune-related pathways. Analyses of individual drinking levels further demonstrated distinct correlations between ethanol intake and astrocytic translation. The major components of the brain extracellular matrix are chondroitin sulfate proteoglycans, produced primarily by astrocytes and covalently bound to chondroitin sulfate glycosaminoglycan chains. Complementary mass spectrometry/liquid chromatography analyses of chondroitin sulfate, heparan sulfate, and hyaluronic acid glycosaminoglycan disaccharides revealed ethanol-induced alterations in chondroitin sulfate glycosaminoglycan sulfation patterns, with additional baseline differences identified between selectively bred high- and low-ethanol preference lines. Together, these findings indicate that astrocytes undergo profound sex- and region-specific adaptations to chronic ethanol, implicating extracellular matrix and glycosaminoglycan remodeling as key risk-factors for and mediators of chronic ethanol-related neuroplasticity.

  PublisherOA PDFDOI

• Arylsulfatase B induces melanoma apoptosis by the ubiquitin ligase COP1

  Journal of Biological Chemistry · 2025-06-23 · 1 citations

  articleOpen access

  Previous experiments in the syngeneic, murine, and subcutaneous model of malignant melanoma and human melanoma cells showed that treatment by recombinant human (rh) Arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) markedly reduced the volume of tumors, improved survival, and inhibited invasiveness. In this report, the impact of ARSB on the progression of metastatic, pulmonary B16F10 melanomas in C57BL/6J mice is addressed, and the underlying apoptotic mechanism by which ARSB inhibits melanoma growth is identified. Exogenous ARSB, which has mannose 6-phosphate attachments, acts through insulin-like growth factor 2 receptor (IGF2R), a cation-independent mannose-6-phosphate receptor, and increases expression of constitutive photomorphogenic protein (COP)1. Expression of COP1, an E3 ubiquitin ligase, is increased by a decline in phospho(Ser473)-AKT1 and an increase in nuclear FOXO3a. ARSB-induced declines in carbohydrate sulfotransferase (CHST)15 expression and in transmembrane receptor tyrosine kinase-like orphan receptor 1 (ROR1) activation mediate the decline in phospho(Ser473)-AKT1. Inverse effects of rhARSB and ARSB knockdown on phospho(Ser473)-AKT1 indicate that ARSB acts as a tumor suppressor and that a decline in ARSB is pro-oncogenic. COP1, which inhibits ultraviolet-B stimulated growth in plants, suppresses nuclear ETS1 and ETS1-mediated expression of BCL2 in the murine melanomas and in human melanoma cells. These effects increase cytoplasmic cytochrome c, caspase-3/7 activation, and apoptosis. Since UVB exposure is recognized as a significant etiological factor in melanoma, identification of COP1 as an inhibitor of melanoma growth suggests the underlying presence of an ARSB-initiated growth inhibitory mechanism, analogous to that in plants, which contributes to the regulation of melanoma progression.

  PublisherOA PDFDOI

• PD-L1 targeted antibody-polymer-Epirubicin conjugate prolongs survival in a preclinical murine model of advanced ovarian cancer

  Journal of Controlled Release · 2025-04-04 · 7 citations

  articleOpen accessSenior author

  T cell activation contributed to a more effective antitumor response. Repeated dosing amplified immunomodulatory effects, leading to durable immunity. These results highlight U6244-051 as a next-generation pADC with high translational potential, offering enhanced efficacy and reduced on-target, off-tumor toxicity.

  PublisherDOI

• Blood-brain barrier crossing biopolymer targeting c-Myc and anti-PD-1 activate primary brain lymphoma immunity: Artificial intelligence analysis

  Journal of Controlled Release · 2025-03-13 · 5 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

Recent grants

• Drug-Free Macromolecular Therapeutics

  NIH · $2.1M · 2011–2031

Frequent coauthors

• Jindřich Kopeček

  University of Utah

  90 shared

• Paul J. Shami

  Huntsman Cancer Institute

  15 shared

• Patrick Keller

  Institut Curie

  12 shared

• D. Christopher Radford

  University of Utah

  12 shared

• Pierre‐Antoine Albouy

  Laboratoire de physique des Solides

  12 shared

• Jiawei Wang

  Yangzhou University

  10 shared

• Douglas W. Sborov

  Huntsman Cancer Institute

  10 shared

• Kuangshi Wu

  9 shared

Labs

• Molecular PharmaceuticsPI

Education

• Ph. D, Molecular and Chemical Engineering

  Peking University

  2001

• B.S, Department of Chemical Engineering

  Tsinghua University

  1986