Human iPS cell derived hepatocyte transplantation studies in mice
Liver is involved in regulation of multiple metabolic pathways and also in metabolism of xenobiotic substances. Until recently, primary human hepatocytes were used to gain insight into liver biology and also to study hepatic drug metabolism. However, limited availability of primary human hepatocytes has necessitated the need for developing alternative sources of human hepatocytes. Several labs have reported directed differentiation of human ES/iPS cells into hepatocytes that closely resemble primary human hepatocytes morphologically and functionally. Additionally, transplantation of human ES cell derived hepatocytes has been shown to engraft and expand in livers of mice models, albeit at much lower efficiency compared to repopulation of mice liver by primary human hepatocytes. My project involves identification of cell surface markers that characterize subset of cells generated during directed differentiation of human ES/iPS cells, specifically at specified hepatic endoderm and immature hepatocyte stage, that can efficiently replace the parenchymal cells of the mouse liver. This will enable expansion of human ES/iPS cell derived hepatocytes and ensure unlimited supply of hepatocytes for research community and also for drug toxicity testing. Additionally, repopulation of mice liver with hepatocytes generated from human iPS cells will make it possible to generate animal models of heritable hepatic disorders.
Education and Training
2005-2010 PhD, University of Nebraska Medical Center, Omaha, USA
2002-2005 MVSc, Indian Veterinary Research Institute, Bareilly, India
1996-2001 BVSc, Veterinary College, University of Agricultural Sciences, Bangalore, India
Noto, F.K., Determan, M.R., Cai, J., Cayo, M.A., Mallanna, S.K., and Duncan, S.A. Aneuploidy is Permissive for Hepatocyte-like Cells Differentiation from Human Induced Pluripotent Stem Cells. BMC Research Notes 2014; 7: 437.
Mallanna, S.K., and Duncan, S.A. Differentiation of Hepatocytes from Pluripotent Stem Cells. Current Protocols in Stem Cell Biology 2013; 1G.4.1-1G.4.13
Mallanna, S.K., and Rizzino, A. Systems Biology Provides New Insights Into the Molecular Mechanisms that Control the Fate of Embryonic Stem Cells. Journal of Cellular Physiology 2012; 227(1): 27-34.
Wuebben E.L., Mallanna, S.K., Cox, J.L., and Rizzino, A. Musashi2 is Required for the Self-renewal and Pluripotency of Embryonic Stem Cells. PLoS ONE 2012; 7(4): e34827.
Gao, Z., Cox, J.L., Gilmore, J.M., Ormsbee, B.D., Mallanna, S.K., Washburn, M.P., and Rizzino, A. Determination of Protein Interactome of Transcription Factor Sox2 in Embryonic Stem Cells Engineered for Inducible Expression of Four Reprogramming Factors. Journal of Biological Chemistry 2012; 287 (14): 11384-97.
Cox, J.L., Mallanna, S.K., Ormsbee, B.D., Desler, M., Wiebe, M.S., and Rizzino, A. Banf1 is Required to Maintain the Self-renewal of Both Mouse and Human Embryonic Stem Cells. Journal of Cell Science 2011. 124(15). 2654-65.
Chakravarthy, H., Ormsbee, B.D., Mallanna, S.K., and Rizzino, A. Rapid Activation of the Bivalent Gene Sox21 Requires Displacement of Multiple Layers of Gene Silencing Machinery. The FASEB Journal 2011; 25(1). 206-218.
Mallanna, S.K., Ormsbee, B.D., Iacovino, M., Gilmore, J.M., Cox, J.L., Kyba, M., Washburn, M., and Rizzino, A. Proteomic Analysis of Sox2-associated Proteins During Early Stages of Mouse Embryonic Stem Cell Differentiation Identifies Sox21 as a Novel Regulator of Stem Cell Fate. Stem Cells 2010; 28(10): 1715-27. # Equal Contribution
Mallanna, S.K., and Rizzino, A. Emerging Roles of microRNAs in the Control of Embryonic Stem Cells and the Generation of Induced Pluripotent Stem Cells. Developmental Biology 2010; 344(1): 16-25.
Cox, J.L., Mallanna, S.K., Luo, X., and Rizzino, A. Sox2 Uses Multiple Domains to Associate with Proteins Present in Sox2-protein Complexes. PLoS ONE 2010; 5(11): e15486.
Mondal, B., Rasool, T.J., Ram, H., and Mallanna, S. Propagation of Vaccine Strain of Duck Enteritis Virus in a Cell Line of Duck Origin as an Alternative Production System to Propagation in Embryonated Egg. Biologicals 2010; 38(3). 401-406.
Boer, B., Cox, J.L., Claassen, D., Mallanna, S.K., Desler, M., and Rizzino, A. Regulation of the Nanog Gene by Both Positive and Negative Cis-regulatory Element in Embryonal Carcinoma Cells and Embryonic Stem Cells. Molecular Reproduction and Development 2009; 76(2): 173-182.
Mallanna, S.K., Boer, B., Desler, M., and Rizzino, A. Differential Regulation of the Oct-3/4 Gene in Cell Culture Model Systems that Parallel Different Stages of Mammalian Development. Molecular Reproduction and Development 2008; 75(8): 1247-1257.
Chakravarthy, H., Boer, B., Desler, M., Mallanna, S.K., McKeithan, T., and Rizzino, A. Identification of DPPA4 and Other Genes as Putative Sox2: Oct-3/4 Target Genes Using a Combination of In silico Analysis and Transcription Based Assays. Journal of Cellular Physiology 2008; 216(3): 651-662.
Boer, B., Kopp, J., Mallanna, S., Desler, M., Chakravarthy, H., Wilder, P., Bernadt, C. and Rizzino, A. Elevating the Levels of Sox2 in Embryonal Carcinoma Cells and Embryonic Stem Cells Inhibits the Expression of Sox2:Oct-3/4 Target Genes. Nucleic Acids Research 2007; 35: 1773-1786.
Mallanna, S.K., Rasool, T.J., Sahay, B., Aleyas, A.G., Ram, H., Mondal, B., Nautiyal, B., Premraj, A., Sreekumar, E., and Yadav, M.P. Inhibition of Anatid Herpes Virus-1 Replication by Small Interfering RNAs in Cell Culture System. Virus Research 2006; 115(2): 192-197.