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Research

Research

Dr. Zheng’s primary research interests:

  1. Type II endometrial carcinogenesis. Dr. Zheng is one of the world's pioneer investigators for this area. In the last 12 years, together with colleagues, collaborators, and trainees, Dr. Zheng has defined the precancer lesions and latent precancers (p53 signature) for type II endometrial cancers. Based on his group’s recent findings, Dr. Zheng has proposed a new model of endometrial serous carcinoma (ESC) development, this model has ESC originating from p53 signature endometrial epithelia to endometrial glandular dysplasia (EmGD) through serous endometrial intraepithelial carcinoma (EIC) and then to ESC. Recently, in collaboration with Dr. Beihua Kong, Dr. Zheng’s group has developed a p53 knockout mouse model by using ksp1.3 and Lox-P system. This mouse model reproduces the exact sequence of the process of endometrial serous carcinoma development. Such a model provides an excellent tool for the study of endometrial serous carcinogenesis and sets the basis for future development of early detection, intervention, and possible prevention of cancer.  
  2. Cell origin of ovarian epithelial cancers. It is known that majority of ovarian high-grade serous carcinomas are derived from the fallopian tubes.  Recently, Dr. Zheng’s group has obtained strong evidence that low-grade ovarian serous carcinoma is mainly derived from tubal epithelial cells.  Zheng’s group has found that tubal epithelia have a tendency to attach to the ovarian surface.  Due to an unclear cause, the attached tubal epithelia can either stay on the ovarian surface (mimicking ovarian surface epithelia morphologically) or get into ovarian stroma forming “endosalpingiosis”.  It is the cells of endosalpingiosis gradually developing into serous cystadenoma, serous borderline tumor, and low-grade serous carcinoma.  Based on their studies, it is also the secretory cells, not ciliated cells, which become serous neoplastic cells including cancers.   Currently, Zheng’s group is studying to determine what molecular basis is required for secretory cells to have the potential of neoplasia.  These updates may have a positive impact in ovarian cancer prevention and management in the near future. 
  3. Cell origin of ovarian endometriosis. There is a long running controversy regarding what is the source for endometriosis. Dr. Zheng defined the earliest morphologic changes of ovarian endometriosis called as initial endometriosis in 2005. This work leads his group to study the etiology of endometriosis and the relationship between endometriosis and endosalpingiosis, and endocervicosis. Based on their recent findings that majority of ovarian endometriosis is derived from tubal fimbria, which forms endosalpingiosis first, then through a metaplastic process to form foci of endometriosis. However, the exact course or initiating factors for this disease process are unknown. At the present, the initial endometriosis provides a useful morphologic model to study the disease mechanism. To extend their work on endometriosis, the cell origin of ovarian clear cell carcinoma and endometrioid carcinoma, which are known to be associated with ovarian endoemtriosis, become a relevant issue. Zheng’s group believes that at least part of these cancers are actually derived from the fallopian tube since approximately 60% of ovarian endometriosis comes from fallopian tube epithelia. 
  4. Cervical cancer early diagnosis and treatment. From a practice perspective, Dr. Zheng has been interested in cervical cancer early diagnosis and one-stop treatment for many years.  Current drawbacks of cervical cancer management modality are the cumbersome lengthy diagnostic procedures and ineffective treatment methods.  Dr. Zheng and his collaborators including Drs. Beihua Kong of Qilu Hospital, Yiying Wang and Yue Wang of Henan Provincial People’s hospital, are currently developing a clinic named "One-Stop Cervical Care" (OSCC) in China.  This program is mainly designed for those patients living in a mobile condition.  They believe that a single visit to such clinics will be adequate for them to identify and treat those precancerous lesions efficiently.  Such new models may contribute to improving overall cervical cancer prevention and control in China.  If this kind of model works well, in 5 years they believe it can be applied to similar populations worldwide. 
  5. Molecular and cellular mechanisms of progestin resistance in patients with endometrial hyperplasia or well differentiated cancers. This is another area of interest for Dr. Zheng’s group.  They have studied the mechanisms of progestin resistance in this setting for more than 10 years.  One advantage for pathologists is to have the priority to use and study human tissue samples.  Zheng’s group has used pre- and post-progestin treated endometrial hyperplasia or cancer samples as the tissue source to address this interesting question.  They have recently identified a unique signal transduction pathway involving Nrf2-AKR1C1 in progestin resistance.  Their continuous studies in this field may improve the overall progestin response rate for estrogen sensitive endometrial neoplastic lesions.