Our lab is honored to recognize our benefactors for their commitment to strengthen medical education and research at Mayo Clinic for the coming generations. Our laboratory space is named for Verdell and Harry Siegel of Albuquerque, New Mexico.
Dr. Gendler was recognized for distinction in her field by the appointment of the David F. and Margaret T. Grohne Research Professorship in Therapeutics in Cancer Research. We thank our generous donors for sponsorship of our research program.
Our laboratory is interested in the role of the MUC1 mucin in cancer. MUC1 is over-expressed and aberrantly glycosylated in most adenocarcinomas of the mammary gland, lung, colon, pancreas, stomach, endometrium, ovary and multiple myelomas; and other hematopoietic malignancies and cells.
Alterations in MUC1 expression or glycosylation accompany the development of cancer and influence cellular growth, transformation,adhesion, invasion, and immune surveillance. Our primary research goals are to determine the function of the transmembrane MUC1 mucin in cell adhesion, tumor progression, metastasis, and modulation of the immune system and to characterize tumor antigens as tumor vaccines. Over-expression of MUC1 in the mouse mammary gland results in tumor formation, indicating that MUC1 is an oncogene.
The tumorigenic function of MUC1 is dependent on the cytoplasmic tail, which is tyrosine phosphorylated and binds to many proteins capable of transducing signals and/or interacting with the cytoskeleton. MUC1 acts as a scaffolding protein to coordinate and enhance multiple growth-promoting and oncogenic signals. In bone marrow cells, lack of Muc1-regulated beta-catenin stability results in aberrant expansion of Cd11b+Gr1+ myeloid-derived suppressor cells, which allows allogeneic tumor growth.
The ubiquitous and aberrant expression of MUC1 on most solid tumors and some hematological tumors suggests that MUC1 is an immunotherapeutic target. We are testing powerful new approaches to immunize animals to MUC1 and other tumor antigens. The goal is the prevention and treatment of spontaneous tumors and metastases of mammary gland, pancreas, and colon. Clinical trials in breast cancer patients,utilizing MUC1/HER-2 peptides, are open.
See my publications