Research
Research projects in the Kannan lab focus on stem cells in regenerative medicine and stem cells in cancer.
Development of Salivary Regenerative Therapy to Treat Xerostomia
This project studies the use of stem cells in regenerative medicine to better manage treatment-related complications in head and neck cancers.
The current standard of care for head and neck cancers is a combination of surgery and radiation therapy. In about 70% of people undergoing this treatment, radiation therapy leads to chronic hyposalivation (xerostomia, also called dry mouth). Radiation therapy causes extensive damage to salivary parenchyma and decreases gland function. The complications of hyposalivation include impaired taste, dental caries, reduced quality of life, and difficulties with speech, food mastication and retaining dentures.
Pharmacotherapy in the form of saliva substitutes or cholinergic agents, such as pilocarpine, an M2 agonist, and cevimeline, an M3 agonist, are often used to stimulate salivary secretion and improve the symptoms but don't offer a durable long-term treatment to this condition.
Dr. Kannan and Jeffrey R. Janus, M.D., an otorhinolaryngologist at Mayo Clinic in Florida, have launched a two-site initiative funded by the Center for Regenerative Biotherapeutics to develop stem cell-based salivary regenerative therapy. Our team is using a chronic hyposalivation mouse model to test functionally intact salivary gland regeneration.
Cellular and Mechanistic Origin of Breast Cancer
In this research project, 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 increase susceptibility to breast cancer. Yet the exact mechanism driving the increased susceptibility is unknown.
Our main goal in this project is to develop preventive treatments that target early-stage breast cancer. We hope to do this through insights into the normal process of mammary cell development and by 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.
We hope 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 the Kannan 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 is to identify novel, lineage-specific tumor suppressive mechanisms operating to counter the mutagenic stress and maintain a healthy mammary gland. Our research may enable 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 this project, we're 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 people at average risk and high risk using the organoid culture system.
Our team 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.