Primary research interest in the lab lies in the basic biology of stem cells. We are also keen on exploring translational applications in humans, domestic animals and wildlife species.
Cloning: It was discovered that undefined factors present in the oocyte cytoplasm can reprogram the epigenome of a transplanted somatic cell nucleus to a totipotent state and develop into live offspring. This process, termed somatic cell nuclear transfer (SCNT) or simply cloning is a prototypic example for the process of cellular dedifferentiation. Although quite extraordinary, the mechanisms underlying this nuclear reprogramming are not understood and the process is extremely inefficient.
Embryonic Stem (ES) Cells: Undifferentiated cells derived from a preimplantation embryo (inner cell mass of a blastocyst) that are capable of self-renewal, and can develop into cells and tissues of the three primary germ layers. Although murine ES cells were derived more than two decades ago, authentic ES cells are yet to be derived for different farm animal species. The reason behind this is that the self-renewal factor(s) required for in vitro ES cell culture that appears to be different for each species is yet to be identified for farm animals.
Induced-Pluripotent Stem (iPS) Cells: It was recently demonstrated that using a defined set of embryonic and facilitative transcription factors it is possible to reprogram adult somatic cells to a primordial embryonic stem cell-like state. These cells called induced pluripotent stem (iPS) cells were phenotypically identical to ES cells. This approach for generating isogenic pluripotent cells has significant potential for regenerative therapies in human medicine. Moreover, the generation of iPS cells from humans with genetic diseases can allow the study of human disease and can also be useful for drug discovery. In domestic and wild mammals, generation of iPS cells will help decipher species differences in the maintenance of the pluripotent state. Moreover, the establishment of an iPS cell-based biomaterial resource bank for vulnerable/endangered species may offer an extremely powerful tool for genome resource banking.
By understanding fundamental mechanisms of underlying nuclear reprogramming and maintenance of the pluripotent state in the above contexts, we believe that we will be able to effectively generate isogenic pluripotent stem cells for multifarious applications and also increase the efficiency of reproductive cloning.
The major objectives of my research program are to:
Understand the epigenetic reprogramming events and mediators during activation of development in the fertilized egg.
Examine the signaling events leading to the establishment of the pluripotency network and the ‘genesis’ of embryonic stem cells in the developing blastocyst.
Dissecting the process of nuclear reprogramming during the generation of iPS cells and also understanding oocyte factors after somatic cell nuclear transfer or ‘cloning.’
Identify the extracellular factors required for maintenance of pluripotency in ES and iPS cells from different species.
Develop applications for stem cells in humans and animals.
To develop novel stem cell-based tools for wildlife preservation.
Selvaraj V. (2012). Biomedical applications of induced pluripotent stem cells. In: Stem cells and cancer stem cells, Vol 3. M.A. Hayat (Ed.), Springer-Verlag, Berlin, Germany. pp. 265-275.
Ambrose W. and Selvaraj V†. (2011). iPS cells: born-again stem cells for biomedical applications. In: Biomedical Engineering, Book 3. B. Ghista (Ed.), Intech Publisher, Rijeka, Croatia.pp. 679-696. †Corresponding author
Cooke PS, Selvaraj V, Yellayi S (2005) [Phytoestrogen effects on immunity.] In: Endocrine Disruptors in Life Science-Molecular Mechanism of Health Effects. T Iguchi and T Inoue (Eds.), Springer-Verlag, Japan, Ltd., Tokyo, Japan, pp. 255-261.
Selvaraj V, Jiang P, Chechneva O, Lo U and Deng W. (2012). Differentiating human stem cells into neurons and glial cells for neural repair. Frontiers in Bioscience. 17:65-89.
Selvaraj V, Wildt D and Pukazhenthi B. (2011). Induced pluripotent stem cells for conserving endangered species? Nature Methods. 8(10): 805-807.
Selvaraj V†, Plane JM, Williams AJ and Deng W. (2010). Switching cell fate: the remarkable rise of iPS and lineage reprogramming technologies. Trends in Biotechnology. 28(4): 214-23. †Corresponding author
Cooke PS, Selvaraj V and Yellayi S. (2006). Genistein, estrogen receptors and the acquired immune response. The Journal of Nutrition. 136(3):704-8.
Soundarapandian M, Selvaraj V, Lo U, Golub M, Feldman D, Pleasure DE and Deng W. (2011). Zfp488 promotes oligodendrocyte differentiation of neural progenitor cells in adult mice after demyelination. Scientific reports. 1:2 doi:10.1038/srep2.
Shanmugam AS, Jadav KK, Illayaraja S and Selvaraj V. (2011). Effects of body weight and season on serum lipid concentrations in sloth bears (Melursus ursinus ursinus). Journal of Zoo and Wildlife Medicine. 42(3): 373-381.
Jiang P, Selvaraj V and Deng W. (2010). Differentiation of embryonic stem cells into oligodendrocyte precursors. Journal of Visualized Experiments. (39). pii: 1960.
Selvaraj V†, Asano A, Page J, Kumar K, Foster J, Nelson JL, Brenna T, Weiss RS and Travis AJ (2010). Mice lacking FABP9/PERF15 develop sperm head abnormalities but are fertile. Developmental Biology. †Corresponding author
Selvaraj V, Soundarapandian M, Williams AJ, Sidorov MK, Soulika A, Pleasure DE and Deng W. (2009). PARP-1 deficiency increases the severity of disease in a mouse model for multiple sclerosis. Journal of Biological Chemistry. 284(38):26070-84.
Selvaraj V, Asano A, Sengupta P, Weiss RS and Travis AJ. (2009). Mechanisms underlying the micron-scale segregation of sterols and GM1 in live mammalian sperm. Journal of Cellular Physiology. 218(3): 522-36.
Asano A, Selvaraj V, Buttke DE, Nelson JL, Green KM, Evans JE and Travis AJ. (2009). Biochemical characterization of membrane fractions in murine sperm: Identification of three distinct sub-types of membrane rafts. Journal of Cellular Physiology. 218(3): 537-48.
Shanmugam AS, Jadav KK, Illayaraja S and Selvaraj V†. (2008). Hematology of sloth bears (Melursus ursinus ursinus) from two locations in India. Journal of Wildlife Diseases. 44(2): 509-18. †Corresponding author
Kim Y, Selvaraj V and Travis AJ. (2007). Effect of donor age on success of spermatogenesis in feline testis xenografts. Reproduction, fertility and development. 19(7): 869-876.
Selvaraj V*, Buttke DE*, Asano A, McElwee JL, Wolff CA, Nelson JL, Klaus AV, Hunnicutt GR and Travis AJ. (2007). GM1 dynamics as a marker for membrane changes associated with the process of capacitation in murine and bovine spermatozoa. Journal of Andrology. 28(4): 588-599. *Equal contributors.
Selvaraj V*, Asano A*, Buttke DE, McElwee JL, Nelson JL, Wolff CA, Merdiushev T, Fornes MW, Cohen AW, Lisanti MP, Rothblat GH, Kopf GS and Travis AJ. (2006). Segregation of micron-scale membrane sub-domains in live murine sperm. Journal of Cellular Physiology. 206(3): 636-646. *Equal contributors.
Kim Y, Selvaraj V, Dobrinski I, Lee H, McEntee MC and Travis AJ. (2006) Recipient preparation and mixed germ cell isolation for spermatogonial stem cell transplantation in domestic cats. Journal of Andrology. 27(2): 248-256.
Selvaraj V, Bunick D, Johnson RW, Liu L, Hwang H and Cooke PS. (2005). Gene expression profiling of 17-beta estradiol and genistein effects on the mouse thymus. Toxicological Sciences. 87(1): 97-112.
Selvaraj V, Zakroczymski MA, Naaz A, Mukai M, Helferich WG, Doerge DR and Cooke PS. (2004). Estrogenicity of equol on reproductive and non-reproductive organs in mice. Biology of Reproduction. 71(3): 966-972.