Wei-Hsiung Yang, Ph.D. - Internal Medicine

contact information:  meowy100@yahoo.com

 

Graduate Training: Mechanisms and Application of Hormone-Toxin Conjugates

I earned my Ph.D. in Dr. Terry Nett’s laboratory at Colorado State University studying the gonadotropin-releasing hormone (GnRH) and GnRH receptors. I focused on three aspects of the applications of GnRH and GnRH receptor: internalization rates of GnRH receptors (i.e., characterization and comparison of the murine and ovine GnRH receptors), cytotoxic activity and stability of GnRH-toxin conjugates (i.e., examination of GnRH-toxin conjugate’s cytotoxicity, stability, and application in GnRH receptor-positive cell lines), and quantitative assessment of GnRH-toxin conjugates (i.e., establishment and development of ELISA for measurement of GnRH-toxin conjugates). These results directly indicate that GnRH-toxin conjugate is a new class of biomedicines that provide a novel approach for inhibiting reproduction and treating cancers, which are dependent on reproductive hormones (such as breast, endometrial, ovarian, and prostate cancers). This work has contributed to the development of GnRH-Pokeweed antiviral protein (GnRH-PAP) conjugate as a reproductive sterilant currently on the clinical trial.

 

Postdoctoral Training: Analysis of Nongenomic Androgen-Mediated Signaling

I finished my first postdoctoral training in Dr. Stephen Hammes’s laboratory at University of Texas Southwestern Medical Center at Dallas studying the role of nongenomic androgen-mediated signaling in oocyte (meiotic) maturation. I focused on three aspects of androgen-mediated oocyte maturation: selective modulation of genomic and nongenomic androgen responses by androgen receptor ligands (i.e., evidence that steroid-induced signal may depend on the type of target cell, the receptor location within cells, as well as ligand itself), ovarian CYP17 expression in oocyte maturation (i.e., evidence that oocytes play a critical role in Xenopus ovarian androgen production), Xenopus CYP17-medicated androgen biosynthesis independent of the cofactor cytochrome b5 (i.e., evidence that CYP17 may therefore have evolved from a general producer of sex steroids in lower vertebrates to a more tightly regulated producer of both sex steroids and glucocorticoids in mammals). This work has contributed to support the new mechanism of oocyte maturation that androgen, as well as progesterone, can promote oocyte maturation and androgen may serve as a physiologic mediator in oocyte maturation in vivo.

 

Current Research Project in Dr. Gary Hammer's lab: Analysis of Transcriptional Activation by Post-Translational Protein Modifications

I study the underlying mechanisms of nuclear receptors’ cyclic recruitment and promoter clearance at University of Michigan. My research focuses on SUMO modification and phosphorylation of orphan nuclear receptor 5A family members.

SF-1, a member of orphan nuclear receptors, is expressed throughout adrenal cortex, testis, ovary, hypothalamus, and anterior pituitary where it regulates a number of genes involved in the biosynthesis of steroid hormones together with genes encoding the insulin/IGF/relaxin family of hormones. Previously, the former graduate student Jon Winnay, by using chromatin immunoprecipitation assay (ChIP) has shown that membrane initiated signals mediated the cyclic recruitment of SF-1-dependent complexes coincident with SF-1 phosphorylation and activation of RNA polymerase II-mediated transcriptional activation (please see Molecular Endocrinology paper). Recent reports demonstrate that SF-1 is SUMOylated and SUMOylated SF-1 attenuates transcriptional activity of SF-1’s target genes. However, the physiological function of post-translational modifications of SF-1 remains to be elucidated. Currently, we further investigate the underlying mechanism(s) of cyclic recruitment and promoter clearance of SF-1-dependent complexes. Our current work aims to establish a working model for the post-translational regulation (SUMOylation and phosphorylation) of SF-1 activity during both the regulated cell growth mediated by ACTH and the ACTH-independent activation of SF-1 evident in adrenal neoplasms. Given the number of oncogenes and tumor suppressor genes that have been defined as targets for SUMOylation, studies on protein SUMOylation may shed light on the mechanism of tumorigenesis and metastasis. I propose that results may provide a foundation for the rational design of novel therapeutic approaches for cancer prevention and treatment.