Chintan Kikani

cki266's picture
  • Assistant Professor
  • Biology
314 Thomas Hunt Morgan Bldg
859-562-2695
Research Interests:
Research Interests: Signaling and transcriptional control of stem cell fate

We are looking for graduate students and post-doctoral fellows to join our team! Please contact us via email.  

We are broadly interested in the study of cellular signaling network and how that shapes animal physiology. Defective regulation of signaling network is an underlying cause of many of the human diseases and is targeted for their interventions. My research group is specifically interested in the study of signaling network in adults stem cells. Adult stem cells are embedded within tissues and in this niche they are continually sampling their environment to choose between self-renewal, proliferation (symmetric or asymmetric), and differentiation. Failure to coordinate these processes could result in regenerative failure, excessive growth, or tissue malfunction. Our group is interested in discovering new pathways, new players, and new mechanisms that control the regenerative functions of adult stem cells. Our multidisciplinary approaches have allowed us to dive deeper into understanding the molecular mechanisms of regeneration. Ultimately, we aspire to translate our findings to develop the next generation of therapeutic approaches to combat diseases such as muscle wasting. 

  1. Signaling and transcriptional control of stem cell fate during regeneration: We have discovered a new signaling pathway in muscle stem cells that connects nutrient signaling to chromatin architecture in muscle stem cells to regulate the myogenesis program. In this pathway, PAS kinase is activated by nutrients such as amino acids and glucose by a mechanistic Target of Rapamycin (mTOR) protein kinase. This activation of PASK is required for the myogenin transcription and the subsequent onset of the myogenesis program during muscle regeneration. We are currently investigating the molecular mechanism by which PASK signals to transcription regulatory network at the myogenin promoter to activate its transcription in muscle stem cells. Our studies have identified WD repeat 5 (Wdr5), a core member of the MLL/Set family of histone H3 Lys4 methyltransferase as a substrate of PASK. Building on these data, we are testing a hypothesis that PASK-Wdr5 signaling facilitates chromatin remodeling to activate the molecular program of myogenesis using cell culture and animal models of muscle regeneration. 
  2. Metabolic network in cancer: Alteration in metabolism is both a necessity and a liability for human cancers. In order to satisfy the demand for accelerated cellular growth, cancer cells rewire their metabolism to divert metabolites into generating biosynthetic precursors, sometimes at the expense of net ATP generation. Amongst many approaches cancer cells employ to achieve metabolic rewiring, we are interested in the study of altered subcellular distribution of signaling and metabolic proteins in cancers. We are pursuing a hypothesis that by altering the subcellular distribution of signaling and metabolic proteins, new pathways and new metabolite pools are being generated to fuel the metabolic rewriting. We have shown that nuclear translocation of a metabolic protein kinase, 3’-Phosphoinositide Dependent Kinase-1 (PDK-1) triggers an oncogenic transformation of fibroblasts and that nuclear PDK1 is accumulated in human prostate cancers. PDK-1 is normally cytoplasmic but accumulates in the nucleus when oncogenic pathways are activated. We are continuing to investigate the mechanistic underpinning of PDK-1 nuclear translocation process and subsequent cellular transformation due to nuclear PDK-1.
PubMed Publications*: 
  • Kikani, CK ;Wu, X.;Fogarty, S ;Kang, SAW ;Dephoure, N ;Gygi, SP ;Sabatini, DM ;Rutter, J "Activation of PASK by mTORC1 is required for the onset of the terminal differentiation program." Proceedings of the National Academy of Sciences of the United States of America 116, 21 (2019): 10382-10391. Details. Full text
  • Kikani, CK ;Wu, X.;Paul, L ;Sabic, H ;Shen, Z ;Shakya, A ;Keefe, A ;Villanueva, C ;Kardon, G ;Graves, B ;Tantin, D ;Rutter, J "Pask integrates hormonal signaling with histone modification via Wdr5 phosphorylation to drive myogenesis." eLife 5, (2016): Details. Full text
  • Wu, X.;Romero, D ;Swiatek, WI ;Dorweiler, I ;Kikani, CK ;Sabic, H ;Zweifel, BS ;McKearn, J ;Blitzer, JT ;Nickols, GA ;Rutter, J "PAS kinase drives lipogenesis through SREBP-1 maturation." Cell reports 8, 1 (2014): 242-55. Details. Full text
  • Kikani, CK ;Verona, EV ;Ryu, J ;Shen, Y ;Ye, Q ;Zheng, L.;Qian, Z.;Sakaue, H ;Nakamura, K.;Du, J ;Ji, Q ;Ogawa, W ;Sun, LZ ;Dong, LQ ;Liu, F. "Proliferative and antiapoptotic signaling stimulated by nuclear-localized PDK1 results in oncogenesis." Science signaling 5, 249 (2012): ra80. Details. Full text
  • Kikani, CK ;Antonysamy, SA ;Bonanno, JB ;Romero, R ;Zhang, FF ;Russell, M ;Gheyi, T ;Iizuka, M ;Emtage, S ;Sauder, JM ;Turk, BE ;Burley, SK ;Rutter, J "Structural bases of PAS domain-regulated kinase (PASK) activation in the absence of activation loop phosphorylation." The Journal of biological chemistry 285, 52 (2010): 41034-43. Details. Full text
  • Wang, C.;Xin, X ;Xiang, R ;Ramos, FJ ;Liu, M.;Lee, HJ ;Chen, H.;Mao, X.;Kikani, CK ;Liu, F.;Dong, LQ "Yin-Yang regulation of adiponectin signaling by APPL isoforms in muscle cells." The Journal of biological chemistry 284, 46 (2009): 31608-15. Details. Full text
  • Wang, L.;Balas, B ;Christ-Roberts, CY ;Kim, RY ;Ramos, FJ ;Kikani, CK ;Li, C.;Deng, C ;Reyna, S ;Musi, N ;Dong, LQ ;DeFronzo, RA ;Liu, F. "Peripheral disruption of the Grb10 gene enhances insulin signaling and sensitivity in vivo." Molecular and cellular biology 27, 18 (2007): 6497-505. Details. Full text
  • Riojas, RA ;Kikani, CK ;Wang, C.;Mao, X.;Zhou, L ;Langlais, PR ;Hu, D ;Roberts, JL ;Dong, LQ ;Liu, F. "Fine tuning PDK1 activity by phosphorylation at Ser163." The Journal of biological chemistry 281, 31 (2006): 21588-93. Details. Full text
  • Mao, X.;Kikani, CK ;Riojas, RA ;Langlais, P ;Wang, L.;Ramos, FJ ;Fang, Q ;Christ-Roberts, CY ;Hong, JY ;Kim, RY ;Liu, F.;Dong, LQ "APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function." Nature cell biology 8, 5 (2006): 516-23. Details. Full text
  • Kikani, CK ;Dong, LQ ;Liu, F. ""New"-clear functions of PDK1: beyond a master kinase in the cytosol?" Journal of cellular biochemistry 96, 6 (2005): 1157-62. Details. Full text
  • Lim, MA ;Kikani, CK ;Wick, MJ ;Dong, LQ "Nuclear translocation of 3'-phosphoinositide-dependent protein kinase 1 (PDK-1): a potential regulatory mechanism for PDK-1 function." Proceedings of the National Academy of Sciences of the United States of America 100, 24 (2003): 14006-11. Details. Full text
* Publications are automatically pulled from pubmed.gov based on a user-specific query. Results may include incorrect citations. See: Tutorial on improving PubMed results.
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