The Pq Laboratory of BiomeDx/Rx
Dx to Rx: The Key to Advancing Precision Medicine
Our research is focused on Translational Medicine. Through working at the interface of medicine, material, and engineering our interdisciplinary team aims to develop groundbreaking technologies for the detection of biofluid biomarkers and drug delivery. Ultimately, we hope that by working in close partnership with medical practitioners, these techniques can be implemented in clinical practice. On the other hand, leveraging clinical data mining we are interested in exploring, identifying, and validating potential biomarkers for disease diagnosis and therapy. We will further bring them back to the patient's bedside to improve outcomes. Currently, our team focuses on lung cancer early diagnosis, treatment monitoring, and drug delivery systems.
Bench-to-Bedside: Lung Cancer Diagnostics
Extracellular vesicles (EVs) are lipid bilayer-enclosed vesicles with sub-micrometer size that are released by cells. EVs contain a tissue-specific signature wherein a variety of proteins and nucleic acids are selectively packaged. Incontestably, growing evidence has shown important biological roles and clinical relevance of EVs in cancers. In particular, recent studies validate that EV can be used for non-invasive repetitive cancer (early) diagnostics, staging, and treatment monitoring. In previous studies, we confirmed the existence of EV DNA. We found EV DNA represents the entire genome, reflects the mutational status, and show identical copy number variation of parental cells. Compared with cell free DNA (cfDNA, average ~160 bp), EV DNA is relatively intact (average ~15 kbp) due to protection of the lipid envelop against DNase. In our cohort study, KRAS and EGFR mutations were identified from plasma EVs isolated from patients with advanced non-small cell lung cancer (NSCLC) and advanced pancreatic cancer. In a pivotal study, we further demonstrated EV DNA is superior to cfDNA for EGFR mutation detection in stage I/II NSCLC. Currently, we are conducting a clinical trial to investigate the role of EV-DNA in early diagnosis of malignant single pulmonary nodule (MSPN). Through the comprehensive investigation of concordance between EV-DNA and tissue DNA, accumulated mutation burden, and mutation hallmark, we would be able to understand the evolution of MSPN. The potential findings including mutation hallmark and sequencing panel could be translated to clinical use for liquid biopsy of MSPN. To further provide a more powerful diagnostic strategy for patients with MSPN, a deep learning artificial intelligence is under development, which can quickly raise a red flag on patients with high risk of MSPN. Subsequently, physicians would recommend these patients take EV-based liquid biopsy. The combination of medical imaging and molecular detection would significantly improve diagnostic accuracy of MSPN with a five-day turnaround time. In contrast, a definitive diagnosis of MSPN generally takes 3 to 12 months, and it heavily relies on follow-up CT scans. The other ongoing project is focusing on the transcriptome of MSPN and its microenvironment. We observed the immunosuppression of major anti-tumor effector cells, such as T cells, B cells, NK cells, and dendritic cells. Moreover, the dynamic changes of the immune cell composition and their molecular characteristics were analyzed as well. Our findings would shed light on the immune evolution from preneoplasia to invasive lung adenocarcinoma. The transcriptome signature of EVs derived from peripheral immune cells could facilitate MSPN screening and early detection.
Bench-to-Bedside: Drug Delivery Nanocarriers
In addition to cancer diagnostics, EVs have also been exploited as drug vehicles for drug delivery. EVs as a natural delivery system can evade phagocytosis, have extended blood half-life, and exhibit optimal biocompatibility without potential long-term safety issues. EVs can fuse with the cell membrane and deliver drugs directly into the cytoplasm. By evading the engulfment by lysosomes, EVs remarkably enhance the delivery efficiency of vulnerable molecules. Additionally, the small size of EVs facilitates their extravasation, translocation through physical barriers, and passage through the extracellular matrix. Recently, we developed engineered EVs for tumor-targeted drug delivery, which can be massively prepared by mechanical extrusion or sonication. We also used engineered EVs derived from mesenchymal stem cells to promote soft tissue wound healing and skin rejuvenation. Later, we developed genetically engineered universal EVs for concurrent cancer immune checkpoint therapy and chemotherapy. Currently, we are developing the next-generation of therapeutic EVs which can specifically bind to receptors on tumor cell membranes and then deliver drugs to the cytosol via highly efficient membrane fusion. Therefore, unprecedentedly high efficacy would be achieved in cancer therapy. Given that clinical-grade EVs for cancer treatment have been produced on a large scale under GMP standards, it is highly possible that our engineered EVs can be translated into clinical use in the future. In addition to EV-based drug delivery nanocarriers, we developed chimeric nanobodies that can spontaneously assemble into lipid bilayers and form cancer-targeting vesicles in one step. This new technology shows promise for industrial manufacturing and clinical translation.
Bedside-to-Bench: Clinical Data Mining
We mine big data in order to find new diagnostic biomarkers, search for new therapeutic targets, and measure the current therapeutic interventions. We extract, analyze, and interpret published clinical data, such as NGS data, efficacy data on drug treatment, and epidemiological data. Nevertheless, in our finished and ongoing studies, we classified lung adenocarcinoma based on gene mutation and immune phenotypes, found potential therapeutic targets for lung cancer patients, demonstrated the significance of statins in the treatment of lung cancer, and observed the role of EOMES+CD8+ T cells in lung cancer EGFR-targeted therapy. Indeed, based on our findings we are designing relevant clinical trials to further validate the identified biomarker and target for lung cancer treatment.
[2023-06] Our paper is accepted to be published in Nature Communication. In this study, we developed virus-mimicking vesicles. These vesicles are equipped with targeting moieties and binding-defective fusogens which can trigger membrane fusion and achieve cytoplasmic drug delivery.
[2022-12] Guosheng's paper is accepted to be published in Drug Resistance Updates with an impact factor of 20+. He reported EOMES+CD8+ T cells could be a marker for the prediction of acquired EGFR-TKI resistance. His hard work and perseverance have paid off. Congratulations!
[2022-11] Leihui Tong's conference paper was accepted by the upcoming 2023 SPIE Medical Imaging: Digital and Computational Pathology for Oral Presentation. Many Congratulations! An awesome achievement for a high school student.
[2022-08] Our perspective is published in the British Journal of Cancer. We speculate that ruptured circulating tumor cells in capillaries could release a large number of small extracellular vesicle-like vesicles, which can encapsulate chromosomal DNA fragments. These vesicles may promote cancer metastasis.
[2021-09] Guosheng's paper is accepted to be published in Clinical and Translational Medicine (with an impact factor of 10+). He reported that anti-cholesterol therapy could benefit NSCLC patients with wild-type EGFR and low-expression of PD-L1.
[2021-09] We have received notice-of-awards for an R37 grant (MERIT Award) from NCI entitled "liquid biopsy of solitary pulmonary nodule with extracellular vesicles".
[2021-07] Our technical paper is accepted to be published in Bioactive Materials (with an impact factor of 10+). The genetically engineered extracellular vesicles can perform concurrent immunotherapy and chemotherapy.
[2019-10] We are excited to publish our first technical paper in Analytical Chemistry.
[2019-08] Miss. Bordenave won the 2nd Place Poster Presentation with "EVs Derived from Cells Cultured in Artificial Microgravity".
[2019-06] The invited News & Views, Enhanced Detection of Tumor-Secreted Vesicles, was published in Nature Biomedical Engineering
[2019-03] Yi's poster got the 1st Prize Poster Award at UNYTE Un-Meeting at the University of Rochester on March 13, 2019.
[2018-08] The Pq Lab of BiomeDx/Rx in Binghamton Univeristy-SUNY was established.