Sigrid P. Dubois, Ph.D.
- Center for Cancer Research
- National Cancer Institute
- Building 10 - Magnuson CC, Room 4B47
- Bethesda, MD 20892-1374
- 240-858-3486
- duboiss@mail.nih.gov
RESEARCH SUMMARY
One of the Dr. Dubois' major contributions has been the characterization of the mechanism of action of IL-15. Instead of acting as a soluble factor, IL-15Ralpha retains IL-15 via a high-affinity interaction on the cell surface and trans-presents it to neighboring NK and CD8+ T cells that express IL-2/15Rbeta and gammac. Studies conducted by Dr. Dubois have helped in understanding the regulation of IL-15 production and its role in the development of some CD8 populations as well as its contribution to the activation/proliferation of NK cells. Dr. Dubois has been involved in the use of IL-15 in the treatment of malignancies in mice, where it has been found to be effective. Ultimately, the work of Dr. Dubois contributed to the GMP production of IL-15 that has been used in a first-in-human clinical trial as a new therapy for patients with metastatic malignant melanoma and renal cell cancer. Currently, two main projects conducted by Dr. Dubois focus on: 1) the role of IL-15 in the development of T cell malignancy, and 2) the development of a new therapy supporting the anti-tumor activity of NK cells.
Areas of Expertise
Sigrid P. Dubois, Ph.D.
Research
The main focus of the laboratory of Dr. Thomas A. Waldmann is the role of Interleukin-2 (IL-2) and IL-15 on the regulation of human immune responses. One of the Dr. Dubois' major contributions has been the characterization of the mechanism of action of IL-15. Instead of acting as a soluble factor, IL-15Ralpha retains IL-15 via a high-affinity interaction on the cell surface and trans-presents it to neighboring NK and CD8+ T cells that express IL-2/15Rbeta and gammac. Studies conducted by Dr. Dubois have helped in understanding the regulation of IL-15 production and its role in the development of some CD8 populations as well as its contribution to the activation/proliferation of NK cells. Dr. Dubois has been involved in the use of IL-15 in the treatment of malignancies in mice, where it has been found to be effective. Ultimately, the work of Dr. Dubois contributed to the GMP production of IL-15 that has been used in a first-in-human clinical trial as a new therapy for patients with metastatic malignant melanoma and renal cell cancer. Currently, two main projects conducted by Dr. Dubois focus on: 1) the role of IL-15 in the development of T cell malignancy, and 2) the development of a new therapy supporting the anti-tumor activity of NK cells.
Publications
Interleukin-15 combined with an anti-CD40 antibody provides enhanced therapeutic efficacy for murine models of colon cancer
Preassociation of IL-15 with IL-15R alpha-IgG1-Fc enhances its activity on proliferation of NK and CD8+/CD44high T cells and its antitumor action
IL-15Ralpha recycles and presents IL-15 In trans to neighboring cells
Paracrine and transpresentation functions of IL-15 are mediated by diverse splice versions of IL-15Ra in human monocytes and dendritic cells
Selective dependence of H2-M3-restricted CD8 responses on IL-15
Biography
Sigrid P. Dubois, Ph.D.
Dr. Sigrid Dubois earned her Ph.D. degree in 1999 from the University of Sciences of Nantes, France. She obtained postdoctoral training in the NCI Lymphoid Malignancies Branch (formerly, Metabolism Branch) where she now serves as a staff scientist in the laboratory of Dr. Thomas A. Waldmann.