My lab has an interest in determining the effects of cancer stem cell and tumor microenvironment in cancer progress, and in gaining an insight into the mechanisms driving tumorigenesis, drug resistance, metastasis, and in developing personalized targeted therapies and precision medicine to treat both drug resistance and metastasis in colon cancer, renal cell carcinoma, pancreatic cancer, bladder cancer, esophageal adenocarcinoma, and B cell lymphoma.
Cancer stemcell and tumor microenvironment
Recently, a new class ofcancer cells has been identified that may be responsible for tumor recurrence.Referred to as tumor initiating cells (TICs), these cells represent a smallpopulation within the original tumor that are resistant to conventional chemotherapeuticand radiation treatments. They also have the ability to produce new (recurrent)tumors that possess all the phenotypic features of the original tumors. We haveidentified such drug resistant TICs in colon cancer, bladder cancer, andfollicular lymphoma cells. These cells are dependent on the LN microenvironmentprovided by LNSCs. Some of the communication between the LNSCs and TICs mayoccur by the transfer of exosomal vesicles, small membrane-bound particlescontaining proteins, siRNAs and mRNAs which have been shown to form functionalsignaling pathways between cells in vivo. We have recently shown apositive effect of stromal cell exosomal vesicle-derived mRNAs and miRNAs ontumor progression.
Patient-derivedorthotopic xenograft models for combination including immune checkpointblockade therapies
To examine the role ofLNSCs in tumor progression and metastasis, we established both in vitro cellculture models and in vivo human-in-mouse orthotopic xenograftmodels using patient tumor specimens, tagged with optical reporter genes. Thesemodels recapitulate human cancer features and provide a useful platform forinvestigating major TIC/LN microenvironment-specific mechanisms of cancerresistance to chemotherapeutic agents in various cancers, such as solid tumorColorectal Cancer, Renal Cell Carcinoma, Bladder Cancer, EsophagealAdenocarcinoma, Pancreatic Cancer, and B Cell Lymphoma. With noninvasiveimaging approaches, the labeled tumor cells can be tracked in vivo,which permits both macroscopic and microscopic analysis of tumor progressionand metastasis. Thus, our models provide a powerful mammalian experimentalsystem to elucidate the mechanisms of cancer initiation, maintenance,progression, and provide platforms for combination including immune check pointinhibitory therapies.
Prognostic andpredictive biomarkers and translate preclinical discoveries into effective curefor cancer patients
The established invitro and in vivo xenograft models will be used asplatforms for dissecting the molecular mechanisms underlying the disseminationof cancer and for preclinical drug development to constitute an integratedbedside to bench approach. As supported by our recent data on renal cell cancerstudies, these models can lead to support identification of biomarkers,optimization of clinical candidate selection, and explore novel therapeuticstrategies targeting tumor microenvironment in general or to evaluateindividual patient tumor cells and predict their response to therapies in anAvatar style approach.
Education:
Shanghai Second Medical University, China
MD
1982
Pediatrics
Shanghai Second Medical University, China
MS
1987
Immunology
Lübeck Medical University, Germany
PhD
1990
Molecular Immunology
Alton Ochsner Medical Foundation, USA
Postdoc
1992
Cellular Immunology
