Triple-negative breast cancer (TNBC) represents one of the most biologically and clinically heterogeneous diseases. It has long been considered as a difficult unmet need because of the lack of any receptors that can be targeted for breast cancer treatment as well as its aggressive behavior and poor prognosis. The complexities and technical challenges require extensive collaborations with multidisciplinary teams and experts. This is a jointed research effort from both basic and clinical health sciences that combines different tools for the improved understanding of the mechanism and the development of effective therapies in the treatment of triple negative breast cancer.
Dr Brian S DeDecker
Synthetic Biology
CU-Boulder team from University of Colorado supervised by Dr. Brian S DeDecker is working on the production of paclitaxel (Taxol) in soy plants. In addition to the known action of paclitaxel on microtubule stabilization, paclitaxel can promote antitumor immunity through the transformation of M2-polarized macrophages to the M1-like phenotype in a TLR4-dependent manner. Our team is focused on the remodeling of acidic and hypoxia tumor microenvironment with genetically engineered bacteria that carry with chemical nano-immunomodulators. The expected clearance of lactic acid and relief of hypoxia are aimed to stop the non-inflammatory polarization of tumor associated macrophages in acidic environment and thus re-boost macrophage driven anti-tumor immune responses. We both teams are exploring ways that can intervene the macrophage M1-M2 polarization.
The genetic engineering is based on the expression of SIRPα that can recognize CD 47 on surfaces of tumor cells. We are collaborating on GoldenBraid to facilitate the engineering of genetic modules in E. coli. Nissle 1917. Dr. Brian helps us establish a system for surface display of proteins on E. coli Nissle 1917.
In molecular biology, we have been investigating the metabolic evolution of E. coli Nissle 1917 that live on lactatic acid. With mass spectrometry, adaptive changes in proteomic and metabolomic networks have been investigated in E. coli Nissle 1917 cells that evolve on lactic acid environment.
Dr Xiaoyun Liu
Microbiology
Dr. Xiaoyun Liu is a professor in school of basic medical science of Peking University. His research focuses on the mechanism of host–microbe interactions that are crucial for normal physiological and immune system development. As we know, most late-stage cancers are either insensitive to chemotherapies or develop resistance later. Live tumour-targeting bacteria provides a unique alternative tool to tackle with these challenges. Compared with other therapeutics, engineered bacteria with tumour-targeting capability can be self-driven to the deep solid tumors that may be inaccessible to conventional passive treatments. They also initiate cascades of innate and adaptive anti-tumor immune responses. In order to better design tumor targeting bacteria, we are interested in the interactions between the host and the bacteria as well as virulence factors catalyzed covalent modifications of proteins.
We have discussed the occurrence of protein modifications in infection and immunity through online Tencent Meeting.
Dr Bifeng Yuan
Public Health
Dr. Bifeng Yuan is a professor and vice dean in School of Public Health of Wuhan University. His group has been working on epigenetic modifications, nucleic acid damage and repair in cancer development and progression. His research makes us to think over the mechanism of triple negative breast cancer from a different direction. Not like genetic changes, epigenetic modifications include DNA methylation, chromatin remodeling and non-coding RNAs without the changes in DNA sequences. It has been demonstrated that TNBC pathogenesis is closely related with epigenetic modifications. Lots of cancer are driven by epigenetic events, which highlights the role of the epigenetic network in TNBC. In fact, the progression of breast cancer involves complex and multi-step processes that represent the accumulation of not only genetic but also epigenetic alterations. Both external and internal factors may drives tumorigenesis.
We discuss techniques of experimental trouble shooting through online Tencent Meeting.
Dr Ping Wang
Hardware Development
Dr. Ping Wang is a professor in Changping laboratory. His group has been working on ultrafast optics and instrumentation as well as the application to molecular imaging of tumors. Ultrafast optics refers to the generation, amplification and manipulation of ultrashort pulses of light in a time scale of the order of femtosecond and below. With the aid of such ultrafast light pulses, it is possible to investigate ultrafast phenomena that are unexplored with conventional techniques. We are inspired by Dr. Ping Wang’s interesting research achievements including (1) near-resonance enhanced label-free stimulated Raman scattering microscopy with spatial resolution near 130 nm; (2) far-field transient absorption nanoscopy with sub-50 nm optical super-resolution; (3) polydiacetylene-based ultrastrong bioorthogonal Raman probes for targeted live-cell Raman imaging.
We discuss techniques of experimental trouble shooting through online Tencent Meeting.