Charles L. Sentman, Ph.D.
Title(s):
Professor of Microbiology and Immunology
Department(s):
Microbiology and Immunology
Education:
University of Texas Southwestern Medical Center, Ph.D. 1990
University of Illinois, B.S., 1985
Dr. Sentman did postdoctoral training at Washington University Medical School in St. Louis, MO on the role of cell death in T cell development. From 1992 to 1995, he conducted postdoctoral research at the Microbiology and Tumor Biology Center at the Karolinska Institute in Stockholm, Sweden on natural killer (NK) cell recognition mechanisms. In 1995 he joined the medical faculty and became an investigator at the Umeå Center for Molecular Pathogenesis at Umeå University, Umeå, Sweden where he continued his research program on NK cell receptors. In 1997, Dr. Sentman received a docentur in molecular immunology from Umeå University. From 1998 to 2001, Dr. Sentman worked as a team leader and section leader at AstraZeneca R&D in Lund, Sweden with the aim to develop new pharmaceuticals against respiratory and inflammation diseases, including asthma and rheumatoid arthritis. In 2001, Dr. Sentman joined the faculty of the department of Microbiology and Immunology at Dartmouth Medical School as an assistant professor.
Programs:
Molecular and Cellular Biology Graduate Programs
Websites:
http:
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Contact Information:
Dartmouth Medical School
Borwell Research Building - HB 7556
1 Medical Center Drive
Lebanon NH 03756
Phone: 603-653-0611
Fax: 603-650-6223
Email: Charles.L.Sentman@Dartmouth.Edu
Professional Interests:
Natural killer (NK) cells are an important part of the innate immune system and have the ability to kill tumor cells and some virus-infected cells while sparing nearby normal cells. Dr. Sentman's research interests have focused on natural killer (NK) cell recognition mechanisms and the role of NK cells as a part of the immune defenses. His laboratory has three major areas of research: chimeric NK cell receptors as immunotherapy, NK cells in tumor immunity, and human NK cell function in the female reproductive tract.
Chimeric NK cell receptors as immunotherapy: NK cells express a number of different receptors that can recognize tumor cells, and it may be possible to use these as a means to target tumors selectively. Dr. Sentman’s lab has developed a novel immunotherapy targeting strategy using chimeric NKG2D receptors. These chimeric NKG2D receptors are formed by a fusion of NKG2D with a cytoplasmic signaling molecule, CD3zeta. NKG2D recognizes several ligands that are often expressed on tumor cells but not normal tissues. Almost 70% of human cancers are of tumor types that have been shown to express ligands for NKG2D. When expressed in T cells by viral transduction, these chimeric NKG2D bearing T cells are able to recognize tumor cells in an MHC independent manner, and they produce proinflammatory cytokines and kill tumor cells upon recognition of their ligands. Dr. Sentman’s laboratory is using this approach to target ovarian cancer, lymphoma, and myeloma, and this approach has the potential to be applied to other tumors such as breast cancer, melanoma, and osteosarcoma.
NK cells in tumor immunity: Dr. Sentman's laboratory is investigating the role of NK cells and NK Ly49 receptors in the development of anti-tumor immune responses. It is known that NK cells are important part of immune responses against tumor cells that have lost expression of MHC class I molecules. However, many tumors express MHC class I molecules. Although NK cells can directly kill tumor cells, long term control of tumor growth likely requires the development of an anti-tumor T cell response. There is a growing appreciation that innate immune recognition is an important early event that helps shape the development of adaptive immune responses. Dr. Sentman's lab is studying how Ly49-MHC class I interactions regulate NK cell responses to syngeneic tumors and how these NK cell responses (or lack of responses) alter the development of anti-tumor T cell responses. The hypothesis under investigation is that tumor cells may interact with NK cells and prevent an effective anti-tumor immune response. This implies that by altering the NK-tumor interaction, it may be possible to promote better long term anti-tumor immunity.
Biology of human NK cell subsets: NK cells are found in the human endometrium in increasing numbers as the menstrual cycle progresses. Data indicate that NK cells play an important role in the development of a proper placental environment during pregnancy. The NK cells found in the uterus (uNK cells) appear to be closely related to the CD56bright subset of blood NK cells, although uNK cells express unique markers not found on blood NK cells. There may be a selective recruitment of cytokine producing NK cells to the uterus in a hormone regulated fashion. Dr. Sentman's laboratory is studying how sex hormones and different cell types in the uterus regulate the recruitment and function of these uNK cells. As a part of the innate immune system, NK cells participate in responses against infectious microorganisms and promote adaptive immune responses. In collaboration with other research groups at Dartmouth, Dr. Sentman is investigating the interaction of NK cells with epithelial cells, macrophages, dendritic cells, and other stromal cells in response to infectious organisms, such as HIV. The results from this project will provide an understanding of NK cell biology within the human mucosa and how sex hormones alter innate immune responses.
Selected Publications: |
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Spear P, Barber A, Rynda-Apple A, Sentman CL Zhang T, Sentman CL Meehan KR, Talebian L, Tosteson TD, Hill JM, Szczepiorkowski Z, Sentman CL, Ernstoff MS Zhang T, Wu MR, Sentman CL Spear P, Barber A, Rynda-Apple A, Sentman CL Iyori M, Zhang T, Pantel H, Gagne BA, Sentman CL Talebian L, Wu JY, Fischer DA, Hill JM, Szczepiorkowski ZM, Ernstoff MS, Sentman CL, Meehan KR Barber A, Sentman CL Zhang T, Sentman CL Meehan KR, Talebian L, Wu J, Hill JM, Szczepiorkowski ZM, Sentman CL, Ernstoff MS |
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