1. Cancer metabolism

Reprogrammed cellular metabolism iscrucial for tumor cells to sustain rapid cell growth and proliferation. Proliferating cells switch to aerobic glycolysis, also known as the Warburg effect, and utilize glucose carbon to generate biosynthetic precursors. To maintain TCA cycle and oxidative phosphorylation, cancer cells increase their consumption of glutamine and divert this alternative carbon source. However, insolid tumors, increased glutamine usage and hypovascularized microenvironment result in limited glutamine availability. Importantly, by using metabolomicsanalysis, glutamine has been shown to be the most strongly depleted metabolites in pancreatic tumors. My previous data demonstrated that in pancreatic cancer cells, microRNA represses aerobic glycolysis promote cell survival upon glutamine deficiency through promoting the utilization of glucose to support the tricarboxylic acid cycle and decreasing glutamine dependence. Thus, I am interested in targeting cellular metabolism as an alternative strategy for pancreatic cancer treatment.

2. Cancer stem cells

The similarities between tumorigenesis and embryonic development have been noticed for some time and are receiving increasing attention, then the cancer stem cell hypothesishas been postulated. I found in ECCs, Akt phosphorylate the master pluripotency factor Oct4, and that the levels of phosphorylated Oct4 correlated with resistance to apoptosis and tumorigenic potential. My data showed that the Aktserine/threonine protein kinase phosphorylated Oct4 at threonine 235 enhanced transcription of core stemness genes and cell survival genes, which tipped the fate of the pluripotent stem cells toward tumorigenesis. I am interested in the strategies to target cancer stem cells for cancer treatment.

3. Type 2 Diabetes

Type 2 diabetes mellitus (T2D), characterized by persistent hyperglycemia, affects over 400 million people worldwide and continues to be a major health problem. Uncontrolled increased blood glucose concentration has been a clinical hallmark of T2D, and can lead to long-term complications including cardiovascular complications, neuropathy, and kidney failure. Despite recent studies elucidating the molecular characterization of T2D, the understanding of the metabolic dysregulation in T2D is still limited, and many diabetic patients still require multiple medications to lower blood glucose. It highlighted the need for more effective T2D therapies. Additionally, some evidence suggests hyperactivation of protein phosphatases in diabetic patients.Thus, my interest is to identify the aberrant changes of protein phosphatase activity in cellular metabolism in T2D and develop potential inhibitors as an ovel and effective therapeutic approach for T2D treatment.

1.Xazmin H. Lowman, Eric A. Hanse, Ying Yang, Mari B. Ishak Gabra, Thai Q.Tran, Haiqing Li, Mei Kong. p53 promotes cancer cell adaptation to glutamine deprivation by upregulating Slc7a3 to increase intracellular arginine levels. Cell Report, 2019, 26: 3051-3060.

2. YingYang, Mari B. Ishak Gabra, Eric A. Hanse, Xazmin H. Lowman, Thai Q. Tran, Haiqing Li, Neta Milman, Juan Liu, Michael A. Reid, Jason W. Locasale, Ziv Giland Mei Kong. MiR-135 suppresses glycolysis and promotes pancreatic cancer cell adaptation to metabolic stress by targeting phosphofructokinase-1. Nature Communications, 2019, 10: 809.

3.Chunjing Bian, Chao Zhang, Aditi Vyas, Shih-Hsun Chen, Chao Liu, Ying Yang,Mei Kong, Tao Luo and Xiaochun Yu. NADP+ is an endogenous PARP inhibitor in DNA damage response and tumor suppression. Nature Communications, 2019, 10: 693.

4.Mari B. Ishak Gabra, Ying Yang, Xazmin H. Lowman, Michael A. Reid, ThaiQ. Tran, and Mei Kong. IKKβ activates p53 to promote cancer cell adaption to glutamine deprivation. Oncogenesis, 2018, 7: 93.

5.Tharindumala Abeywardana, Myungeun Oh, Lei Jiang, Ying Yang, Mei Kong,Jikui Song and Yanzhong Yang. CARM1 suppresses de novo serine synthesis by promoting PKM2 activity. Journal of Biological Chemistry, 2018 Aug 21.

6. ThaiQ. Tran, Mari B. Ishak Gabra, Xazmin H. Lowman, Ying Yang, Michael A.Reid, Min Pan, Timothy R. O’Connor, Mei Kong. Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes. Plos Biology, 2017 Nov 6;15 (11): e2002810

7. Wenxin Li, Yanwen Zhou, Xiaoqian Zhang, Ying Yang, Songsong Dan, TongSu, Shiqi She, Weilai Dong, Qingwei Zhao, Jia Jia, Hangping Yao, Min Zheng, BoKang, Yingjie Wang. Dual inhibiting OCT4 and AKT potently suppresses the propagation of human cancer cells. Scientific Reports 7, 46246 (2017)

8.Thai Q Tran, Xazmin H Lowman, Michael A Reid, Mendez-Dorantes C, Min Pan, YingYang, Mei Kong. Tumor-associated mutant p53 promotes cancer cell survivalupon glutamine deprivation through p21 induction. Oncogene 10/2016: onc.2016.360.

9.Pan M, Reid MA, Lowman XH, Kulkarni RP, Tran TQ, Liu X, Yang Y,Hernandez-Davies JE, Rosales KK, Li H, Hugo W, Song C, Xu X, Schones DE, Ann DK, Gradinaru V, Lo RS, Locasale JW, Kong M. Regional glutamine deficiency in tumours promotes dedifferentiation through inhibition of histone demethylation. Nature Cell Biology 10/2016; 18(10):1090-101.

10.Reid MA, Lowman XH, Pan M, Tran TQ, Warmoes MO, Ishak Gabra MB, Yang Y, Locasale JW, Kong M. IKK beta promotes metabolic adaptation to glutamine deprivation via phosphorylation and inhibition of PFKFB3. Gene and Development 08/2016; 30(16):1837-51.

11.Rosales KR, Reid MA, Yang Y, Tran TQ, Wang WI, Lowman X, Pan M, Kong M.TIPRL inhibits protein phosphatase 4 activity and promotes H2AX phosphorylationin the DNA damage response. Plos One12/2015; 10(12): e0145938.

12.Jenny Davies, Thai Tran, Kimberly Rosales, Michael Reid, Xazmin Lowman, MinPan, Ying Yang, Wu Jun, Roger S. Lo, Mei Kong. Vemurafenib resistance reprograms melanoma cells towards glutamine dependence. Journal of Translational Medicine 7/2015; 13:210.

13.Jie Cheng, Wenxin Li, Bo Kang, Jiasheng Song, Yanwen Zhou, Songsong Dan, YingYang, Xiaoqian Zhang, Jingchao Li, Shengyong Yin, Hongcui Cao, HangpingYao, Chenggang Zhum Wen Yi, Qingwei Zhao, Min Zheng, Shusen Zheng, Lanjuan Li,Binghui Shen, Yingjie Wang. Tryptophan derivatives regulate the transcription of Oct4 in stem-like cancer cells. Nature Communications. 6/2015; 6:7209.

14.Ning Zhou, Jianzhou Li, Yimin Zhang, Juan Lu, Ermei Chen, Weibo Du, Jie Wang,Xiaoping Pan, Danhua Zhu, Ying Yang, Yu Chen, Hongcui Cao, Lanjuan Li. Efficacyof coupled low-volume plasma exchange with plasma filtration adsorption intreating pigs with acute liver failure: A randomised study. Journal of Hepatology, 8/2015;63(2):378-87.

15.Qingwei Zhao, Yanwen Zhou, Wenxin Li, Bo Kang, Xiaoqian Zhang, Ying Yang,Jie Cheng, Sheng Yong Yin, Ying Tong, Jianqin He, Hangping Yao, Min Zheng,Yingjie Wang. Akt-mediated phosphorylation of Oct4 is associated with theproliferation of stem-like cancer cells. Oncology Reports, 2015 April 33(4): 1621-1629

16.Ying Yang*, Jianzhou Li*, Xiaoping Pan, Pengcheng Zhou, Xiaopeng Yu,Hongcui Cao, Yingjie Wang, Lanjian Li. Co-culture with mesenchymal stem cellsenhances metabolic functions of liver cells in bioartificial liver system. Biotechnology and Bioengineering, 2013 Mar;110(3):958-68. (*co-first authors)

17.Yuanji Lin*, Ying Yang*, Weihua Li*, Qi Chen*, JieLi, Xiao Pan, Lina Zhou, Changwei Liu, Chunsong Chen, Jianqin He, Hongcui Cao,Hangping Yao, Li Zheng, Xiaowei Xu, Zongping Xia, Jiangtao Ren, Lei Xiao,Lanjuan Li, Binghui Shen, Honglin Zhou, and Yingjie Wang. Reciprocal regulationof Akt and Oct4 promotes the self-renewal and survival of embryonal carcinomacells. Molecular Cell, 2012. Nov30;48(4):627-40. (*co-first authors)

18. YingYang, Jianzhou Li, Xiaoping Pan, Pengcheng Zhou, Xiaopeng Yu, Hongcui Cao,Yingjie Wang, Lanjuan Li. The study on hepatocytes culture model based on microsphere suspension fluidized bed bioreactor. Second National Severe chronicviral hepatitis of basic and clinical research progress in academic conferences. Chongqing, China. Jan 1, 2012.

19.Lifu Zhao, Jianzhou Li, Guoliang Lv, Anye Zhang, Pengcheng Zhou, Ying Yang,Xiaoping Pan, Xiaopeng Yu, Yimin Zhang, Shusen Zheng, Yu Chen, Yuemei Chen,Chengbo Yu, Weibo Du, Tao Song, Jiansheng Xu, Yang Yu and Lanjuan Li.Evaluation of a reversibly immortalized human hepatocyte line in bioartificial liver in pigs. African Journal of biotechnology,2012. Feb 28; 11(17): 4116-4128.

20.Lifu Zhao, Guoliang Lv, Yimin Zhang, Anye Zhang, Jianzhou Li, Pengcheng Zhou,Xiaoping Pan, Yuemei Chen, Xiaopeng Yu, Chengbo Yu, Wei Xu, Ying Yang, LanjuanLi. Development of a Novel Artificial Liver Support System. 4^TH International Conference on Biomedical Engineering and Informatics (BMEI),(2011)

21. Ying Yang, Jun Yang.Construction of the Plasmid Encoding the Fusion Protein of Hepatocyte GrowthFactor and Red Fluorescent Protein. Journal of Biomedical Engineering, 2009 Dec;26(6):1286-90.

22. Guoguang Niu, Ying Yang,Hongbin Zhang, Jun Yang, Li Song, Zhou Yang, Hui Cao, Yudong Zheng, Siquan Zhu,Huai Yang. Synthesis and Characterization of Acrylamide / N-vinylpyrrolidone Copolymer with Pendent Thiol Groups for Ophthalmic Applications. Acta Biomater, 2009,5(4):1056-63