Regulation of Ovarian Cancer Metastasis
We study the regulation of metastatic colonization of ovarian cancer through the reciprocal interactions between cancer cells and the metastatic microenvironment
5/15/19: Yiming won the 1st prize for best poster at the IUSCC Cancer Research Day. He was also chosen to give a talk on his research. Congratulations Yiming!!!
1/7/19: Melissa Halprin joins the lab as an undergraduate researcher. Welcome Melissa!
12/15/18: First year CMCB graduate student Ishara Moulana joins the lab to pursue her Ph.D. Welcome Ishara!
11/7/18: Congratulations Yiming for passing your prelims with flying colors!
7/16/18: A warm welcome to Kartikeya who joins the group today as a postdoctoral scholar.
5/17/18: We are featured in a New York Times article by Susan Gubar: https://nyti.ms/2k1tEoS
5/3/18: Congratulations Yiming for being awarded the honorable mention prize in the IU Simon Cancer Center's Cancer Research Day!!!
5/1/18: A warm welcome to Mohamed who joins the group today as a visiting scholar.
Role of reciprocal interactions between cancer cells and their microenvironment in regulation of ovarian cancer metastasis.
Ovarian cancer is the most lethal of all gynecologic malignancies primarily because most ovarian cancer patients present with extensive metastasis when they are first diagnosed. There has been no significant improvement in survival rates over the last three decades. Metastasis is responsible for most cancer related deaths and is one of the least understood aspects of the disease. Therefore, it is imperative to understand the process of ovarian cancer metastasis and devise new therapies targeting metastatic disease. Ovarian cancer has a unique metastasis, which rarely takes the hematogenous route. During the process of abdominal dissemination, the cancer cells floating in the peritoneal fluid have to attach to the mesothelial cells lining the peritoneal organs and interact with the microenvironment at the site of metastasis to successfully establish metastatic colonies. The cross talk between the cancer cells with the microenvironment of the metastasis site and the regulation of the initial steps of colonization is crucial and largely unknown.
My laboratory seeks to understand the paracrine and juxtacrine interactions between cancer cells and their microenvironment that regulate metastatic colonization in ovarian cancer. We are using in vitro organotypic 3D culture models (Figure 1), live 3D time lapse microscopy and mouse xenograft models of metastasis along with cell and molecular biological approaches to study the reciprocal interactions between the metastasizing cancer cells with their microenvironment at the site of metastasis. We are specifically interested in the regulation of key microRNAs and transcription factors by these paracrine/juxtacrine interactions and the mechanism by which they drive metastatic colonization in ovarian cancer. We have developed novel assays like a plug homing assay, a 3D time-lapse confocal microscopy based assay for co-invasion of cancer cells along with stromal cells and a proximal culture method to study paracrine signaling.
Time lapse confocal imaging of invasion of ovarian cancer cells (green) through a monolayer of mesothelial cells (red)
Time lapse confocal imaging of co-invasion of ovarian cancer cells (green) and cancer associated fibroblasts (red) through matrigel.
Immunofluorescence imaging of cocultured OVCAR3 cells (green) and cancer associated fibroblasts (red).
Yiming's immunofluorescence image made it to the cover of "The Tumor Microenvironment of High Grade Serous Ovarian Cancer".
Proximal Culture Method: We have developed a novel Proximal Culture method to study paracrine signaling between cancer cells and their microenvironment (J. Vis. Exp. (138), e58144).
Subramanyam Dasari, Ph.D.
Ph.D., Dravidian University, India.
My long-term research interests involve the development of a comprehensive understanding of the interactions of microenvironment with ovarian cancer cells during establishment of ovarian cancer metastasis and devise new therapies targeting metastatic disease. Currently, we are seeking to understand the reciprocal interactions between ovarian cancer cells and the tumor microenvironment for the regulation of metastatic colonization in ovarian cancer through microRNAs.
Frank Cheng, Ph.D.
Ph.D., National Chung Cheng University, Taiwan.
I am interested in studying microenvironment regulated transcription factors in ovarian cancer that promote metastasis. I am also interested in the regulation of key microRNAs by the interactions with microenvironment that leads to ovarian cancer metastasis and stemness.
Yiming Fang, B.S.
Biochemistry Graduate Program Ph.D. Student
B.S., Sun Yat-sen University, China.
I am interested in understanding the role of the tumor microenvironment in providing a cancer stem cell niche and how that can lead to chemoresistance.
Ji Wang, M.D.
Cell, Molecular and Cancer Biology Ph.D. Student
M.D., Huazhong University of Science and Technology, China.
My research is mainly about epigenetic regulation of miRNAs and transcription factors regulating omental metastasis of ovarian cancer using Single-Cell Sequencing techniques. In addition to research, my everyday goal here is to lead a happy life in Bloomington.
Xue Xiao (Sherry), B.S.
Cell, Molecular and Cancer Biology Ph.D. Student
B.S., ShanghaiTech University, China.
The focus of my research is to understand the mechanism of ovarian cancer stem cells induction by cancer associate fibroblasts.
I'm a junior studying biology, concentrating in cell biology and molecular genetics. My focus in the lab is to study how microRNAs, specifically miR-193b, affect the metastasis of ovarian cancer .
Sunil Tomar (Postdoc)
Kartikeya Tiwari (Postdoc)
Mohamed A. Abd El Aziz, M.D. (Visiting Scholar)
Ishara Moulana (Graduate Student)
James Haley (MS Student)
Sen Xiong (Undergrad student)
Joshua Scantland (MD student)
Ovarian Cancer Academy Award
From the Department of Defense (DoD) Ovarian Cancer Research Program (OCRP)
Pilot Award from The Marsha Rivkin Center for Ovarian Cancer Research
Pilot Award from Colleen's Dream Foundation
Ralph W. and Grace M. Showalter Research Award
CTSI Core Pilot Grant
Mitra Lab Photos