2023 Mentored Investigator Grant Recipient — Andres Valdivia, PhD
Andres Valdivia, PhD
Northwestern University
Complement Activation at the Interface Between Cancer Cells and Adipocytes
Project Summary
Ovarian Cancer (OC) is the fifth leading cause of cancer death among women in the US and the most common cause of gynecologic cancer death. OC cells have a predilection to form metastasis in the in the fat-rich tissue protecting the organs called omentum. This organ is primarily form by adipocytes and it has been previously reported that the cytokines and lipids secreted by these cells can enhance the survival of invading OC cells. Using a model of co-culture system we generate in our lab we found using RNAseq analysis, that the interaction with adipocytes increase the expression of complement proteins C3 and C5 in OC cells. These proteins that belong to the innate immune system normally play a role during viral and bacterial infections, however their role in cancer remains controversial. In our project we hypothesize that during the interaction of OC and adipocytes, the lipid transfer between adipocytes and tumor cells upregulates C3 and C5, contributing to the increased invasive characteristics of OC cells and that this signaling pathway is critical for OC metastasis and progression. Successful completion of this project will result in a better understanding of the interaction between the OC cells and adipocytes and a new mechanistic understanding of the roll of C3 and C5 during the process of metastasis of cancer cells to the peritoneum. These findings could in turn lead to potential targets to combat cancer in early stages of metastatic progression.
Bio
Dr. Andres Valdivia is currently a postdoctoral researcher in the laboratory of Dr. Daniela Matei in the Robert H Lurie Medical Research Center of Northwestern University. Andres graduated with an undergraduate degree in Biology from the Pontificia Universidad Catolica de Chile. Later he obtained a Masters in Biological science and Ph.D. in Physiology from the same university. During his Ph.D. thesis Andres work focused on understanding the process of tumor irrigation and metastasis in ovarian cancer, with an emphasis on the process of angiogenesis and vasculogenic mimicry. Later in 2019, Andres Joined the laboratory of Dr. Daniela Matei. Here, his work focusses mainly on the study of the interaction between cancer cells and adipocytes and the design of new co-culture models for the study of the metastatic process. With OCRA support, Andres is interested in further understanding the mechanism of the interaction between cancer and adipocytes and aims to determine the ways in which the immune system complement proteins C3 and C5 play a critical role in the interface of the two cell type interaction.