We are interested in many targets.
Thanks to the SMM, we have the power to decode many 'undruggable' protein targets and solve medical problems in a novel way!
T cell Exhaustion
T cell exhaustion is a dysfunctional state of T cells that arises during chronic infections and cancer, where persistent antigen exposure and immunosuppressive signals from the tumor microenvironment impair T cell function. In cancer, exhausted T cells (Tex) show reduced cytokine production (e.g., IFN-γ, TNF-α), diminished proliferative capacity, and sustained expression of inhibitory receptors such as PD-1, TIM-3, and LAG-3. This state limits the immune system’s ability to eliminate tumors and is a major barrier to effective immunotherapy. Understanding and reversing T cell exhaustion—through checkpoint blockade or transcriptional/epigenetic reprogramming—is a key focus in cancer immunotherapy research.
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We realize that many transcription factors could affect the CD8+ T cell fate in the tumor. In the figure above, NFAT de-phosphorylation followed by translocating to nuclear forms a triplex as NFAT-IRF4-BATF, which inhibits TCF1, a T cell activator of the process. Instead, the TOX and NR4As are upregulated, which increases the inhibitory receptors expression and decreases the cytokine level. In addition, EOMES upregulation is also a sign of T cell exhaustion, which brings the increase of inhibitory receptors.​ Our goal is to seek small molecule regulators of the proteins in this diagram, and recover the T cells from the exhausted stage. ​
Epigenetic Regulation in TME
Epigenetic regulation plays a critical role in shaping the tumor microenvironment (TME) by modulating gene expression without altering the DNA sequence. In cancer, epigenetic changes such as DNA methylation, histone modifications, and non-coding RNA expression affect both tumor and immune cells, influencing processes like immune evasion, inflammation, and stromal remodeling. These alterations contribute to immunosuppression, tumor progression, and resistance to therapy, making epigenetic modifiers promising targets for reprogramming the TME and enhancing anti-tumor immunity.
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We focus on regulating the histone modifications to control the gene alterations in the tumor, leading to anti-cancer activities. We aim to make novel drugs which contains tissue/cell type selectivity to reduce the systematic toxicity and improve the potency and tumor penetration.
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Anti-fibrosis Drug Discovery
We developed liver/lung selective templates to help small molecule to accumulate in these target tissues. Our goal is to improve the systematic toxicity of the current medicines in liver fibrosis and lung fibrosis and overcome the low efficacy. Our project is under collaboration with Dr. Oyelere lab in Georgia Tech, and the in vivo data is promising in reversing the fibrosis process.
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Our goal is to develop this series of drugs into a pre-clinical study and optimize the structure to a bioavailable chemical with optimized PK/PD properties.
Anti-thrombosis Drug Discovery
Thrombosis is the key reason for heart attack. The current anti-thrombosis medicines are either too strong or too weak to control the level of thrombosis, leading to hemorrhage (not able to stop bleeding), or no effect on thrombosis process.
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With the Dr. Chen collaboration in University of Texas Medical Branch, we are actively seeking for promising anti-thrombosis drug which could strongly but not completely inhibit the vWF-A1::GP1B-alpha interaction. With this strategy, we found a lead candidate with promising anti-thrombosis effect at the maximum effect of 80% in high dosage. Our goal is to optimize the drug and move forward to pre-clinic study.