Periasamy Selvaraj, PhD
Pathology & Laboratory Medicine
Email Address: email@example.com
B.S. Chemistry, 1975 - 1975
M.S. Biochemistry, 1977 - 1977
Ph.D. Biochemistry, 1984 - 1984
Post Doc Immunology, 1984 - 1988
- Structure and function on Fc receptors Fc receptors for IgG (FcgR) are involved in phagocytosis, antibody-dependent cellular cytotoxicity, and removal of immune complexes from blood circulation. FcgR III (CD16) is expressed in macrophages, granulocytes and NK cells. CD16 on granulocytes is phosphatidyl inositol glycan (GPI) anchored whereas the CD16 expressed on NK cells and macrophages is polypeptide anchored. These two membrane anchor isoforms of CD16 differ in triggering signals for tumor cell cytotoxicity and phagocytosis. Further structure-function studies will be carried out on membrane isoforms of CD16. We have also identified that the avidity state of FcgRII is regulated by cell activation. Future studies will focus on the defining the molecular mechanisms involved in regulation of affinity of FcgRII molecule expressed on human neutrophils.
- Development of 'artificial cancer cell vaccines' using protein transfer Tumors modified by transfecting genes for immunostimulatory molecules such as B7 and cytokines are now considered as a potential therapeutic tumor vaccine. However, transfection is not always efficient and can be difficult with many cell types, especially freshly isolated tumor cells from patients. Moreover, transfection of genes requires the introduction of vectors of viral origin which is not desirable for human therapeutic purposes. Studies have shown that purified GPI-anchored cell surface proteins can be spontaneously incorporated into membranes by incubating the proteins with the cells or cell membranes (Protein Transfer). This unique property can be used to reconstitute cell surface expression receptors on cell membranes without the use of gene transfection. Using recombinant techniques, we have developed many immunostimulatory molecules including B7-1, IL-2, GM-CSF and IL-12 as GPI-anchored form. Currently we are using protein transfer to express these molecules to develop cancer vaccines for breast cancer and melanoma. In the long term the knowledge obtained from this study could be used to develop an 'artificial cell vaccine' to treat cancer.
Honors / Awards:
- Research Fellow, Harvard Medical School, 1988-1990
- Instructor, Department of Pathology, Harvard Medical School, 1988-1990
- Research Fellow, Wellcome Research Unit, Christian Medical College, 1979-1984
Selected/Most Recent Publications:
Published and Accepted Research Articles -
- 44. Bumgarner GW, Shashidharamurthy R, Nagarajan S, DÕSouza MJ, and Selvaraj P. Surface engineering of microparticles using a novel protein transfer technique: Potential applications in targeted drug delivery and vaccine adjuvant development. J. Contrl. Release 2009; 137:90-97 PMID: 19328830
- 41. Shashidharamurthy R, Hennigar RA, Fuchs A, Palaniswami P and Selvaraj P. Extravasation and emigration of neutrophils tothe inflammatory site depend on the interaction of imjmune-complex with Fcy receptors and can be effectively blocked by decoy Fcy receptors. Blood 111: 894-904.
- 42. Selvaraj P, Yerra A, Tien L., Shashidharamurthy R. Custom designing therapeutic cancer vaccines: Delivery of immunostimulatory molecule adjuvants by protein transfer. Hum. Vaccin. 4: (5).
- 37. SkountzouI, Quan FS, Gangadhara S, Ye L, Vzorov A, Selvaraj P, Jacob J, Compans RW, Kang SM. Incorporation of glycoslphosphatidylinositol-anchored granulocyte-macrophage colony-stimulating factor or CD40 ligad enhances immunogenicity of chimeric simian imunodeficiency virus-like particles. J. Virol. 81:1083-94.
- 40. Shashidharamurthy R, Amaro A, Ezekwudo E and Selvaraj P. Analysis of competitive interaction of H and R allelic forms of CD32A with rabbit IgG immune-complex. Proc. Intl. Cong. Immunol. p 513-522.
- 38. LiP, Jiang N, Nagarajan S, Wohlhueter R, Selvaraj P and zhu C. Affinity and Kinetic Analysis of Fcy Receptor IIIa (CD16a) Binding to IgG Ligands. J. Biol. Chem. 282:6210-21.
- 35. Long M, Chen J, Jiang N, Selvaraj P, McEver RP and Zhu, C. Probabilistic modeling of rosette formation mediated by CD16B-hIgG and selectin-ligand interactions. Biophys J. 91:352-363
- 36. Wang YC, Sashidharamurthy R, Nagarajan S and Selvaraj P. B7-1-HSA (CD80-CD24), a recombiant hybrid costimulatory molecule retains ligand binding and costimulatory functions. Immunol Lett. 105:185-192
- 34. Nagarajan S and Selvaraj P. Human tumor membrane vesicles modified to express glycolipid-anchored IL-12 by protein transfer induce T cell proliferation in vitro: a protential approach for local delivery of cytokines during vaccination. Vaccine 14:2264-74.
- 30. Bumgarner GW, Zampell JC, Nagarajan S, Poloso NJ, Dorn AS, D'Souza MJ, Selvaraj P. Modified cell ELISA to determine the solubilization of cell surface proteins:Applications in GPI-anchored protein purification. J Biochem Biophys Methods. 64:99-109.
- 31. Nagarajan S, Fifadara NH, Selvaraj P. Signal-specific activation and regulation of human neutrophil Fc gamma receptors. J Immunol.174:5423-32.
- 33. Zhang F, Marcus WD, Goyal NH, Selvaraj P, Spring TA and Zhu C. Two-dimensional kinetics regulation of &alphaL&Beta2-ICAM-1 interaction by conformational changes of the &alphaL insterted domain. J. Biol. Chem. 280:42207-18.
- 32. Bumgarner, GW, Nagarajan, S, Poloso, N.J., Dorn, AS, D'Souza MJ, and P. Selvaraj. Modified cell ELISA to determine the solubilization of cell surface proteins: Applications in GPI-anchored protein purification. J. Biochem. Biophs. Methods 65:99-109.
- 28. Nagarajan, S, Li, P., C. Zhu and P. Selvaraj. Recombinant CD16A-Ig forms a homodimer and cross-blocks the ligand binding functions of neutrophil and monocyte Fcg Receptors. Mol. Immunol. 38:527-38.
- 29. Poloso NJ, Nagarajan S, Meji-Oneta JM and Selvaraj P. GPI-anchoring of GM-CSF results in active membrane-bound and partially shed cytokine. Mol Immunol. 38:803-16.
Books Edited and Written -
- 39. Selvaraj P. T cell Response. Encyclopedia of Cancer (Edited by Dr. Manfred Schwab, Springer-Verlag Berlin and Heidelberg GmbH & Co).
Other Publications -
- 43. Ezekwudo D, Shashidharamurthy R, Devineni D, Bozeman E, Palaniappan R and Selvaraj P. Inhibition of expression of anti-apoptotic protein Bcl-1 and induction of cell death in radioresistant human prostate adenocarcinoma cell line (PC-3) by methyl jasmonate. Cancer Letters (In Press).