Research in the Yu Lab

Research in my lab primarily focuses on the study of neuroendocrine prostate cancer. Prostate cancer (PCa) is the most common non-skin cancer and the second leading cause of cancer-related deaths among American men. Androgen deprivation therapy is the gold standard treatment for advanced PCa. Patients initially respond well, resulting in tumor regression, but the tumors ultimately progress to castrate-resistant PCa. Moreover, once PCa becomes castrate-resistant, an aggressive neuroendocrine (NE) phenotype ensues with high morbidity and an average survival of less than 1.5 years. There is currently no effective treatment for PCa with a prominent NE phenotype. Identifying the mechanisms through which the NE phenotype arises is critical for the development of novel therapeutics against PCa.

Project 1: Androgen deprivation activates Wnt/beta-Catenin signaling in prostate cancer

The Wnt/beta-Catenin signaling pathway is prevalent in advanced PCa. We have previously shown that activation of Wnt/beta-Catenin signaling promotes the development of castrate-resistant PCa with an increased NE phenotype, thus linking the active Wnt/beta-Catenin signaling with castrate-resistant progression and the emergence of NE phenotype in PCa. In this project, we study the mechanisms that activate Wnt/beta-Catenin signaling in PCa and the involvement of stromal/epithelial interactions in this process.

Project 2: The involvement of FOXA2, a Wnt/beta-Catenin target gene, in PCa progression

We have previously shown that FOXA2, a Forkhead transcription factor, is expressed in NEPCa. We have also shown that SOX2, a well-established “stemness” gene, is expressed in NEPCa, linking the disease with stem cell features. Furthermore, our research indicates that activation of Wnt/beta-Catenin signaling in the prostate induces the expression of FOXA2 and SOX2. In this project, we study the implication of FOXA2 as well as other stemness genes in PCa progression

Project 3: Notch signaling in PCa progression

Notch signaling plays a critical role in both embryo development and cancer progression. In this project, we study the dynamic change of Notch signaling pathway during NEPCa progression and its crosstalk with Wnt/beta-Catenin and Hippo signaling pathways.

Project 4: HOXB13 in PCa progression

Homeobox-containing proteins (HOXs) regulates body segmentation and organogenesis during embryo development. HOXB13, the most posterior HOXB gene, is primarily expressed in prostate. In our study, we found that HOXB13 expression is reduced/lost in NEPCa. Additionally, we have evidence supporting that HOX code is changed in NEPCa.

Selected Publications

1. Siyuan Cheng, Nestor Prieto-Dominguez, Shu Yang, Zachary M. Connelly, Samantha StPierre, Bryce Rushing, Andy Watkins, Lawrence Shi, Meredith Lakey, Lyndsey Buckner Baiamonte, Tajammul Fazili, Aubrey Lurie, Eva Corey, Runhua Shi, Yunshin Yeh, & Xiuping Yu The expression of YAP1 is increased in high-grade prostatic adenocarcinoma but is reduced in neuroendocrine prostate cancer Prostate Cancer and Prostatic Diseases (2020) PMID: 32313141
2. Yunshin Yeh, Qiaozhi Guo, Zachary Connelly, Siyuan Cheng, Shu Yang, Nestor Prieto-Dominguez, Xiuping Yu Wnt/Beta-Catenin Signaling and Prostate Cancer Therapy Resistance Prostate Cancer Adv Exp Med Biol. 2019;1210:351-378
3. Siyuan Cheng and Xiuping Yu Bioinformatics analyses of publicly available NEPCa datasets, Am J Clin Exp Urol. 2019;7(5):327-340
4. Yunshin A Yeh, Shu Yang, Michael Constantinescu, Catherine Chaudoir, Anthony Tanner, Mishala Henry, Sheila Anderson, Juan-Sebastian Saldivar, Faye Serkin, Tajammul Fazili, Aubrey A Lurie, and Xiuping Yu Prostatic adenocarcinoma with novel NTRK3 gene fusion: a case report Am J Clin Exp Urol. 2019; 7(5): 341–345.
5. Connelly, Zachary M., Shu Yang, Fenghua Chen, Yunshin Yeh, Nazih Khater, Renjie Jin, Robert Matusik, and Xiuping Yu. "Foxa2 activates the transcription of androgen receptor target genes in castrate resistant prostatic tumors." Am J Clin Exp Urol. 6, no. 5 (2018): 172.
6. Yang S, Jiang M, Grabowska MM, Li J, Connelly Z, Zhang J, Hayward SW, Cates JM, Han G, Yu X. Androgen receptor differentially regulates the proliferation of prostatic epithelial cells in vitro and in vivo Oncotarget. 2016 Oct 25;7(43):70404-70419 PMID: 27611945
7. Yu X, Matusik RJ, Jin R RNASEL R4620 mutation in prostate cancer. Gene Cell Tissue. 2015 January; 2(1): e24411
8. Yu X, Cates JM, Morrissey C, You C, Grabowska MM, Zhang J, DeGraff DJ, Strand DW, Franco OE, Lin-Tsai O, Hayward SW, Matusik RJ. SOX2 expression in the developing and adult prostate, as well as in benign and malignant pathological states. Prostate Cancer and Prostatic Dis, 2014 Dec;17(4):301-9. PMID: 25091041
9. Gupta A, Yu X, Case T, Paul M, Shen MM, Kaestner KH, Matusik RJ. Mash1 expression is induced in neuroendocrine prostate cancer upon the loss of Foxa2. Prostate. 2013 May; 73(6): 582-9:  PMID: 23060003
10. Yu X, Wang Y, DeGraff DJ, Wills ML, Matusik RJ. Wnt/β-catenin activation promotes prostate tumor progression in a mouse model. Oncogene. 2011 Apr 21; 30(16): 1868-79. PMID: 21151173

Post-doctoral Fellows

While we are not currently recruiting Post-doctoral Fellows, quality candidates will always be considered.  To enquire about opportunities, contact Dr. Yu at xiuping.yu@lsuhs.edu.

Graduate Students

Graduate students interested in conducting research in the Yu lab should review the current laboratory research directions and contact Dr. Yu at xiuping.yu@lsuhs.edu.

Undergraduate Research Assistants

We are not currently hiring any additional undergraduates.