The Gynecologic Oncology (G.O.) Discovery Lab, directed by Dr. Sanaz Memarzadeh, focuses on two poorly understood and under studied epithelial gynecologic malignancies: endometrial and ovarian carcinoma. Even though both cancer subtypes pose a serious health risk to women little is known about what cells give rise to each tumor subtype, how these tumors initiate or strategies for targeted therapy. The goal of the laboratory is to identify ovarian and endometrial cancer initiating cells and targeting genetic pathways essential for their survival as part of the treatment for these gynecologic cancers. The G.O. Discovery team hypothesizes that the normal stem cells in the endometrium or ovary/fallopian tube could be the target cell for formation of endometrial or ovarian papillary serous carcinoma, respectively. The normal epithelial stem of these gynecologic organs may also be precursors for ovarian and endometrial cancer stem cells. The lab aims to pinpoint the genetic changes that prompt normal gynecologic epithelial stem cells to convert into cancer cells and identify the chemical and biologic molecules that can be used to stop their growth. Such new therapies could be better tolerated with fewer side effects and better chances of eradicating these women’s cancers.
Selected Cancer-Related Publications:
Janzen DM, Tiourin E, Salehi JA, Paik DY, Lu J, Pellegrini M, Memarzadeh S. An apoptosis-enhancing drug overcomes platinum resistance in a tumour-initiating subpopulation of ovarian cancer. Nat Commun. 2015 Aug 3;6:7956. doi: 10.1038/ncomms8956.
Janzen DM, Cheng D, Schafenacker AM, Paik DY, Goldstein AS, Witte ON, Jaroszewicz A, Pellegrini M, Memarzadeh S. Estrogen and progesterone together expand murine endometrial epithelial progenitor cells. Stem Cells. 2013 Apr;31(4):808-22. doi: 10.1002/stem.1337.
Janzen DM, Rosales MA, Paik DY, Lee DS, Smith DA, Witte ON, Iruela-Arispe ML, Memarzadeh S. Progesterone receptor signaling in the microenvironment of endometrial cancer influences its response to hormonal therapy. Cancer Res. 2013 Aug 1;73(15):4697-710. doi: 10.1158/0008-5472.CAN-13-0930. Epub 2013 Jun 6.
Paik DY, Janzen DM, Schafenacker AM, Velasco VS, Shung MS, Cheng D, Huang J, Witte ON, Memarzadeh S. Stem-like epithelial cells are concentrated in the distal end of the fallopian tube: a site for injury and serous cancer initiation. Stem Cells. 2012 Nov;30(11):2487-97. doi: 10.1002/stem.1207.
Memarzadeh S, Zong Y, Janzen DM, Goldstein AS, Cheng D, Kurita T, Schafenacker AM, Huang J, Witte ON. Cell-autonomous activation of the PI3-kinase pathway initiates endometrial cancer from adult uterine epithelium. Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17298-303. Epub 2010 Sep 20.