Scientific Publications

The success of passive immunotherapies targeting Calcitonin gene-related peptide (CGRP) for managing migraine has prompted our efforts towards developing an active immunotherapy that induces the production of endogenous antibodies against CGRP. Achieving efficacious antibody titers via immunization could provide a more convenient and cost-effective treatment alternative to anti-CGRP monoclonal antibody (mAb) therapies. However, immunization against endogenous CGRP faces multiple challenges such as breaking immune tolerance, inducing sufficient antibody titers, and avoiding immune response-associated toxicity.

• Link: https://www.nature.com/articles/s43856-025-00870-2

Celastrol (CEL) is a natural pentacyclic triterpenoid demonstrating significant therapeutic properties against various diseases. However, the ambiguity of target information poses a significant challenge in transitioning CEL from a traditional remedy to a modern pharmaceutical agent. Recently, the emerging target discovery approaches of natural products have broadened extensive avenues for uncovering comprehensive target information of CEL and promoting its drug development. Herein, diverse target discovery strategies are overviewed for the pharmacological and toxicological studies of CEL, including chemical proteomics, protein microarray, degradation-based protein profiling, proteome-wide label-free approaches, network pharmacology, target-based drug screening, multi-omics analysis, and hypothesis-driven target confirmation.

• Link: https://onlinelibrary.wiley.com/doi/10.1002/EXP.20240247

A high proliferation rate of cancer cells requires increased protein synthesis leading to ER stress, a condition characterized by accumulation of unfolded or misfolded proteins in the ER lumen. Three interconnected Unfolded Protein Response (UPR) pathways, IRE1, PERK, and ATF6 pathways, are activated to relieve ER stress or to initiate apoptosis if prolonged strong ER stress remains unsolved. Thus, the chronically elevated ER stress levels in cancer cells constitute an Achilles’ heel and provide a window of opportunity for development of therapeutic regimens.

• Link: https://aacrjournals.org/cancerres/article/85/8_Supplement_1/3045/755540/Abstract-3045-Development-of-a-first-in-class

Despite the success of immune checkpoint blockers (ICBs), predicting which patients will respond to treatment remains a significant challenge, particularly in those with advanced NSCLC. Some circulating antibodies may serve as indicators of a pre-existing antitumor adaptive immune response. This study investigated the potential of baseline serum antibodies as predictors of response and survival in patients with advanced NSCLC undergoing ICB, chemotherapy, or ICB + chemotherapy.

• Link: https://aacrjournals.org/cancerres/article/85/8_Supplement_1/6042/759856/Abstract-6042-Baseline-serum-level-of-IgG

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo.

• Link: https://www.sciencedirect.com/science/article/pii/S2211383525000656?via%3Dihub

Metastasis remains the leading cause of cancer mortality. The natural product brusatol (Bru) has exhibited promising anticancer activity; however, the target proteins of Bru and the underlying mechanisms in suppressing tumor metastasis remain unclear.

• Link: https://www.sciencedirect.com/science/article/abs/pii/S0944711325001096?via%3Dihub

At the convergence point of multiple cytokine signals, signal transducer and activator of transcription 3 (STAT3) is a highly promising therapeutic target for diabetic nephropathy. Isoquercitrin, a natural small-molecule inhibitor of STAT3, may have beneficial effects on diabetic nephropathy; however, the underlying mechanism remains unclear. Isoquercitrin significantly mitigated renal inflammation and fibrosis by inhibiting STAT3 activity in mice with diabetic nephropathy.

• Link: https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202414587

Current HIV vaccine strategies are hampered by difficulty with recapitulating heavily mutated broadly neutralizing antibodies. We have previously isolated a highly mutated antibody termed “group C 76-Q13-6F5” (6F5) that uses immunoglobulin heavy chain variable region (VH)1-02. 6F5 targets a conformational epitope on HIV gp41 and mediates Ab-dependent cell cytotoxicity (ADCC). Reverting the group C 76 antibodies’ variable chain to VH1-02 germline in antibody 76Canc showed retained ADCC activity. A vaccine targeting an epitope functionally recognized by germline antibodies offers a distinct advantage.

• Link: https://journals.asm.org/doi/10.1128/spectrum.01911-24

To describe the use of high-throughput whole-human proteome phage immunoprecipitation sequencing (PhIP-Seq) in identifying potential antigens for antibody-negative autoimmune limbic encephalitis (ALE).

• Link: https://link.springer.com/article/10.1007/s00415-025-13039-7

Histidine triad nucleotide-binding protein 1 (HINT1) is related to depression. However, the underlying mechanisms and whether HINT1 is a therapeutic target for depression remain unclear. In this study, we report that loganin, an antidepressant candidate from our previous research, directly targets HINT1 to alleviate depressive-like behaviors. Overexpression of HINT1 in the hippocampus induces depressive-like behaviors.

• Link: https://www.nature.com/articles/s41380-025-02959-5