Stem Cells In Cancer Research
Developing a better understanding of stem cell differentiation processes and the biology of cancer risk can help lead to better cancer treatments. Our lab is engaged in two research projects to study the origins of breast cancer and serous cancers.
Cellular and Mechanistic Origin of Breast Cancer
In this project, titled Cellular and Mechanistic Origin of Breast Cancer, our lab is studying cancer-initiating mechanisms in breast epithelial stem cells and progenitor cells from people with hereditary pathogenic mutations.
It has been known for decades that aging and hereditary pathogenic mutations make a woman increasingly susceptible to breast cancer. Yet the exact mechanism driving the increased susceptibility is unknown.
Given the increasing number of older women anticipated in the next decade, the burden of supporting breast cancer treatments will rise to unprecedented levels.
In this project, our overarching goal is to develop preventive treatments targeting early-stage breast cancer through insights into the normal process of mammary cell development and identifying age-related and mutation-related changes that predispose the development of breast cancer.
To help facilitate this project, Dr. Kannan has collaborated with Mayo Clinic breast surgeons and researchers to create a live breast organoid biobank from average-risk and high-risk people carrying such gene mutations as BRCA1, BRCA2, ATM, PALB2 and CHEK2.
Stem cells and progenitor cells of epithelial origin have been successfully isolated from healthy tissue. Scientists lack a detailed understanding of cell molecular states, transitions, properties, latent differentiation potential, and intrinsic or extrinsic regulators of transcriptional networks and how these change with age.
Dr. Kannan hopes to pinpoint age-specific and mutation-specific alterations that create high-risk normal cells as a first step toward creating new methods for their detection before overt cancer develops and for their elimination by new targeting approaches.
Another major focus in Dr. Kannan's lab is investigating DNA quality-control mechanisms in breast epithelial stem and progenitor cells. Human mammary glands have two distinct epithelial cell lineages. These cells differ in their epigenomic landscape, which reflects their divergent functions. The two lineages also differ in quality and quantity of telomere and mutagenic oxidative DNA lesions. It's plausible that cells of different mammary lineages experience different mutagenic stress.
The goal of this project in Dr. Kannan's lab is to identify novel, lineage-specific tumor suppressive mechanisms operating to counter the mutagenic stress and maintain a healthy mammary gland. Research in this project may allow early detection of breast cancer and could lead to preventive therapies for people at an increased risk of breast cancer.
Cellular and Mechanistic Origin of High-Grade Serous Cancers
In a project titled Cellular and Mechanistic Origin of High-Grade Serous Cancers, Dr. Kannan's lab is studying cancer-initiating mechanisms in fallopian tube epithelial stem cells from people with hereditary pathogenic mutations.
The origin of high-grade serous cancers is linked to fallopian tube cells, but its precise origin is unknown. We're interested in characterizing fallopian tube stem cells from fimbriated and ampullary regions of fallopian tubes from average-risk and high-risk people using the organoid culture system.
Our group has also developed orthotopic (oviduct and ovary) xenotransplantation models to investigate the long-term developmental fate of genome-edited human fallopian tube stem cells.
Dr. Kannan is collaborating with Mayo Clinic colleagues Mark E. Sherman, M.D., and Jamie N. Bakkum-Gamez, M.D. Our team hopes to pinpoint specific molecular alterations that create cancer precursor cells as a first step toward creating new methods for their detection before serous tubal in situ carcinoma (STIC) develops and for their elimination by new targeting approaches.