Nil Ratan Saha, PhD, Staff Scientist
Benaroya Research Institute at Virginia Mason
1201 9th Avenue, Seattle, WA 98101
Phone: (206) 341-1312 (Office) , (206) 583-6400 (Lab)
Fax: (206) 583-2297
E-mail: nsaha@benaroyaresearch.org
Research Interests
Evolutionary development and molecular genetics of the vertebrate adaptive immune system, interactions between adaptive and innate immune systems and immune-endocrine interactions.
Ongoing Research
A novel system of lymphocyte receptors capable of producing enormous diversity by somatic rearrangement of leucine rich repeat (LRR) motifs has been discovered in the lamprey, a primitive vertebrate that exhibits adaptive immunity without having any of the hallmark components of adaptive immunity in higher vertebrates, namely, rearranging genes of the immunoglobulin superfamily, and goes against dogma concerning the origins and function of adaptive immunity. These receptors are named variable lymphocyte receptors (VLRs). We have also discovered variable lymphocyte receptors genes in hagfish, which is the most primitive living member of vertebrates and together with lampreys, make up the subphylum ‘agnatha’. All of these lymphocyte receptors are hypervariable and capable of generating tremendous receptor diversity by virtue of an entirely different molecular and genetic toolkit in which large banks of accessory LRRs are used as cassettes in the “diversity” region. These cassettes are being actively inserted into the germline gene from the other part of the genome during lymphocyte development. By implication to other known LRR-containing proteins such as the Toll-like receptors, the ectodomains of the VLRs, largely comprised of the LRRs, are assumed to be capable of pathogen recognition. There are many fundamental questions yet to be worked out. Most recently we have shown that the VLRs are also implicated in developmental processes in addition to their importance in the immune system.
I am also working on the CD4 and CD8 molecules of zebrafish. As we know, CD4 and CD8 are co-receptor molecules which cooperate with the T-cell receptor in recognizing antigens presented by MHC II and MHC I molecules, respectively. My research mainly focused on the overall structural composition, genomic organization, chromosomal mapping, expression and preparation of CD4 and CD8 transgenic zebrafish.
Lastly, I am working on characterization of immune molecule genes in the genomes of various vertebrates, including the coelacanth and the lamprey.
Publications
Saha, N. R., Smith, J. J., and Amemiya, C. T. 2010. Evolution of adaptive immune recognition in jawless vertebrates. Seminars in Immunology 22: 25-33.
Amemiya, C.T., Saha, N.R., Zapata, A. (2007). Evolution and development of immunological structures in the lamprey. Current Opinion in Immunology 19:535-541.
Saha, N.R., Bei, J-X, Suetake, H., Araki, K., Kai, W., Kikuchi, K., Lin, H-R., Suzuki, Y. (2007). Description of a fugu CXC chemokine and two CXC receptor genes, and characterization of the effects of different stimulators on their expression. Mol. Immunol. 23: 1324-1332.
Hamuro, K., Suetake, H., Saha, N.R., Kikuchi, K., Suzuki, Y. (2007). A teleost polymeric Ig receptor exhibiting two Ig-like domains transports tetrameric IgM into the skin. J Immunol 178: 5682-5689.
Saha, N.R., Suetake, H., Kikuchi, K., Suzuki, Y. (2006). Effects of steroid hormones on the apoptosis and IgM production of LPS-stimulated lymphocytes in the fugu, Takifugu rubripes. Fish. Sci. 72: 136-142.
Suetake, H., Saha, N.R., Araki, K., Akatsu, K., Kikuchi, K., Suzuki, Y (2006). Lymphocyte surface marker genes in fugu. Comp. Biochem. Physiol. Part D1: 102-108.
Saha, N.R., Suetake, H., Suzuki, Y. (2005). Analysis and characterization of the expression of the secretory and membrane forms of IgM heavy chains in the puffer fish, Takifugu rubripes. Mol. Immunol. 42: 113-124
Pancer, Z., Saha, N.R, Kasamatsu, J., Suzuki, T., Amemiya, C.T., Kasahara, M., Cooper, M.D. (2005). Variable lymphocyte receptors in hagfish. Proceedings of the National Academy of Sciences USA 102: 9224-9229.
Saha, N.R., Usami, T., Suzuki, Y. (2004). In vitro effects of steroid hormones on IgM-secreting cells and IgM secretion in common carp (Cyprinus carpio). Fish Shellfish Immunol. 17: 149-158
Saha, N.R., Suetake, H., Suzuki, Y. (2004). Characterization and expression of the immunoglobulin light chain in the fugu: evidence of a solitaire type. Immunogenetics 56: 47-55
Saha, N.R., Suetake, H., Kikuchi, K., Suzuki, Y. (2004). Fugu immunoglobulin D: a highly unusual gene with unprecedented duplications in its constant region. Immunogenetics 56: 438-447
Saha, N.R., Usami, T., Suzuki Y (2003). A double staining flow cytometric assay for the detection of steroid induced apoptotic leucocytes in common carp (Cyprinus carpio). Dev. Comp. Immunol. 27: 351-363
Saha, N.R., Usami, T., Suzuki, Y. (2002). Relationship between immune and reproductive endocrine systems in fish. Fish. Sci. 68 (supl II): 1135-1138
Saha, N.R., Usami, T., Saito T, Suetake H, Suzuki Y (2002). Seasonal changes in the immune activities of common carp (Cyprinus carpio). Fish Physiol. Biochem. 26: 379-387