The laboratory of Virginia M. Shapiro, Ph.D., focuses on the molecular machinery that regulates the development and activation of T cells, a type of blood cell that specializes in fighting pathogens. Defects in this developmental process can leave patients more susceptible to infections or burdened by T cells that attack healthy tissue, resulting in autoimmune disease.
Dr. Shapiro and her colleagues also study the earliest steps in hematopoiesis, the process by which all cells of the blood are generated. All of these processes are guided by transcriptional regulators that control expression of genes critical for the development or function of blood cells at each stage. In addition, Dr. Shapiro is studying how changes in the incorporation of sialic acid into cell surface glycoproteins alter the immune response.
- Regulation of T cell development. As T cells develop, they progress through a tightly regulated series of developmental stages with associated quality control checkpoints. The transition between stages is controlled by transcriptional regulators. Dr. Shapiro's lab is studying the role of several molecules that bind to and modify specific genomic sequences during these steps.
- Regulation of T cell maturation and activation. In the final step of their development, T cells progress from an inert state to one in which they can respond to pathogens. Dr. Shapiro's lab is investigating the regulation of this step by several molecules that control gene expression, as well as by a pathway that alters proteins on the cell surface.
- Regulation of the immune response by sialylated proteins. Proteins on the cell surface are modified by glycosylation, with the terminal modification consisting of sialic acid. Sialic acids on the cell surface interact with receptors on neighboring cells. Engagement of a family of sialic acid receptors (Siglecs) inhibit the activation of the immune system, which is being studied in Dr. Shapiro's lab.
Significance to patient care
The progression of T cells through a series of developmental stages ensures the production of a large repertoire of T cells able to respond to pathogens, while eliminating those with the potential to attack healthy tissues. Failures in T cell development lead to self-reactive T cells that cause diseases, including arthritis, diabetes and asthma. Early hematopoiesis produces all the cells in the blood, and defects in hematopoiesis result in anemias and cytopenias.
Dr. Shapiro's lab is investigating several of the key genetic regulators of T cell processes, which will help uncover novel molecular targets for treating diseases involving immune and hematopoietic failures. Dr. Shapiro is also investigating how changes in sialic acid present on the cell surface alter the immune response to cancer.
- Associate dean for Faculty Affairs, Mayo Clinic Graduate School of Biomedical Sciences, 2019-present
- Platform leader, Infection, Immunity, Inflammation and Fibrosis, Center for Biomedical Discovery, Mayo Clinic, 2015-present
- Vice chair, Department of Immunology, 2015-present
- Recipient, Dean's Recognition Award, Mayo Clinic Graduate School of Biomedical Sciences, 2019
- Standing member, Molecular and Cellular Hematology Study Section, National Institutes of Health, 2018-2024
- Chair, Nominating Committee, American Association of Immunologists, 2018-2020
- Executive council, Autumn Immunology Conference (workshop chair 2015, secretary 2016 and chair 2017, councilor 2018)
- Chair, Committee on the Status of Women, American Association of Immunologists 2014-2017
- Teacher of the Year, Mayo Clinic Graduate School of Biomedical Sciences, 2012