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REJJI KURUVILLA
Biology

Rejji Kuruvilla

Associate Professor

 
224A Mudd Hall
Department of Biology
Johns Hopkins University
3400 N. Charles Street
Baltimore, MD 21218-2685
 
Email: rkuruvilla@jhu.edu
Office 410 516-2366
Lab 410 516-7641
Departmental fax 410 516-5213
 

B.S.

Calcutta University, India

Ph.D.

University of Houston, Texas, USA

Postdoctoral

Johns Hopkins University - School of Medicine, USA

Research Interests

Trafficking of neurotrophins and their receptors in nervous system development: The functioning of the nervous system relies on the establishment of precise neuronal circuits. These neuronal circuits are largely formed during early development. To form functional neuronal circuits, neurons receive specific information in the form of extracellular cues from the target tissues that they innervate. To date, the family of neurotrophins provides the best example of these target-derived instructive cues that regulate diverse developmental events in the vertebrate nervous system, including survival, axonal and dendritic growth and synapse formation. Using a combination of cell biological, biochemical and imaging techniques as well as mouse genetics, we are actively pursuing two lines of research:
  1. How neurotrophic factors coordinate neuronal development by regulating the neuronal endocytic machinery, and
  2. Growth factor signaling pathways underlying axonal growth, morphology and innervation of target tissues during development.
For decades, it has been known that neurotrophins and their receptors undergo long-range trafficking in neurons, but how neurotrophins utilize the trafficking machinery to regulate distinct aspects of neuronal development remains poorly characterized. Using a combination of fluorescent, biochemical and electron microscopic assays, we are currently investigating molecular mechanisms of endocytosis, recycling and long-distance axonal transport of neurotrophins and their receptors in developing neurons.

Role of sympathetic innervation in pancreas development: Post-ganglionic sympathetic neurons innervate a variety of peripheral targets to regulate tissue homeostasis. Sympathetic dysfunction is associated with prevalent diseases including peripheral neuropathies, diabetes and congestive heart failure, which may originate from developmental perturbations in the innervation of sympathetic target tissues. We recently found that sympathetic innervation is necessary for the formation of the pancreatic islets of Langerhans and for their functional maturation (Borden et. al, Cell Reports, 2013). Our study reveals that islet architecture requires extrinsic inductive cues from neighboring tissues such as sympathetic nerves, and suggests that early perturbations in sympathetic innervation might underlie metabolic disorders. The immediate directions for this project are to identify the nerve-derived signals and characterize the signaling pathways activated in islet cells that regulate islet structure and acquisition of functional maturation. These studies will provide new insight into islet development, and will have important implications for current translational efforts to identify factors critical for the onset of pancreatic dysfunction.

Representative Publications

Philip Borden, Jessica Houtz, Steven D. Leach, Rejji Kuruvilla.  Sympathetic innervation during development is necessary for pancreatic islet architecture and functional maturation. Cell Reports. 2013. July 25;4(2):287-301.

Oscar Marcelo Lazo, Andres Gonzalez, Maria Ascano, Rejji Kuruvilla, Andres Couve, and Francisca Bronfman. BDNF regulates Rab11-mediated recycling endosome dynamics to induce dendritic branchingJ. Neuroscience. 2013. Apr 3;33(14):6112-22.

Shih-Kuo Chen, Kylie S. Chew, David S. McNeill, Patrick W. Keeley, Jennifer L. Ecker, Buqing Q. Mao, Johan Pahlberg, Bright Kim, Sammy C.S. Lee, Michael Fox, William Guido, Kwoon Y. Wong, Alapakkam P. Sampath, Benjamin E. Reese, Rejji Kuruvilla,* and Samer Hattar*. Apoptosis regulates ipRGC spacing necessary for rods and cones to drive circadian photoentrainment. Neuron. 2013 Feb 6;77(3):503-15.
*co-corresponding authors.

Yun Kyoung Ryu, King Yu Lo, Sarah Collins, Haiqing Zhao* and Rejji Kuruvilla*. An autocrine Wnt5a-Ror signaling loop mediates sympathetic target innervation. Developmental Biology. 2013 Feb 27.
*co-corresponding authors.

Henry Ho, Michael Susman, Jay Bikoff, Yun Kyoung Ryu, Andrea Jonas, Linda Hu, Rejji Kuruvilla and Michael E. Greenberg. Wnt5a-Ror-Dishevelled signaling constitutes a core developmental pathway that controls tissue morphogenesis. Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4044-51. Epub 2012 Feb 17

Maria Ascano, Daniel Bodmer and Rejji Kuruvilla. Endocytic trafficking of neurotrophins in neural development. Trends Cell Biol. 2012 Mar 21. [Epub ahead of print]

Daniel Bodmer*, Maria Ascaño* and Rejji Kuruvilla, 2011. Isoform-specific dephosphorylation of dynamin1 by calcineurin couples neurotrophin receptor endocytosis to axonal growth. Neuron 70, 1085-1099.
* Equal authors.

Alissa Armstrong, Yun Kyoung Ryu, Deanna Chieco and Rejji Kuruvilla. 2011. Frizzled3 is required for neurogenesis and target innervation during sympathetic nervous system development. J. Neuroscience 31 (7):2371–2381

Ascaño, M., Richmond, A., Borden, P., and Kuruvilla, R.. 2009. Axonal Targeting of Trk Receptors via Transcytosis Regulates Sensitivity to Neurotrophin Responses. J. Neuroscience 29:11674-11685

Daniel Bodmer, Seamus Levine-Wilkinson, Alissa Richmond, Sarah Hirsh and Rejji Kuruvilla, 2009. Wnt5a mediates NGF-dependent axonal branching and growth in developing sympathetic neurons. J. Neuroscience 29 (23):7569-7581

Larry S. Zweifel, Rejji Kuruvilla, and David D. Ginty, 2005. Functions and Mechanisms of Retrograde Neurotrophin Signaling. Nature Reviews Neuroscience 6, 615-625.

Gregorio Valdez, Wendy Akmentin, Polyxeni Philippidou, Rejji Kuruvilla, David D. Ginty and Simon Halegoua, 2005. Pincher-mediated macroendocytosis underlies retrograde signaling by neurotrophin receptors. J. Neuroscience 25 (21), 5236-5247.

Chen, X., Haihong, Y., Kuruvilla R., Ramanan, N., Scangos, K.W., Zhan, C., Nicolas M. Johnson, N.M., Pamela M. England, Kevan M. Shokat and David D. Ginty. 2005. A chemical–genetic approach to studying neurotrophin signaling. Neuron 46, 13-21.

Rejji Kuruvilla * , Larry Zweifel * , Natalia Glebova, Bonnie Lonze, Haihong Ye and David Ginty. 2004. A neurotrophin signaling cascade coordinates sympathetic neuron development through differential control of TrkA trafficking and retrograde signaling. Cell 118, 1-20.
* Equal authors.

Haihong Ye * , Rejji Kuruvilla * , Larry Zweifel and David Ginty. 2003. Evidence in support of signaling endosome-based retrograde survival of sympathetic neurons. Neuron 39, 57-68.
* Equal authors.

Cristinel Miinea, Rejji Kuruvilla, Houra Merrikh and Joseph Eichberg. 2002. Altered arachidonic acid biosynthesis and antioxidant protection mechanisms in Schwann cells grown in elevated glucose. J. Neurochem. 81:1253-1262.

Rejji Kuruvilla, Haihong Ye and David Ginty. 2000. Spatially and functionally distinct roles of the PI3-K effector pathway during NGF signaling in sympathetic neurons. Neuron 27:499-512.

Rejji Kuruvilla and Joseph Eichberg. 1998. Depletion of phospholipid arachidonoyl-containing molecular species in a human Schwann cell line grown in elevated glucose and their restoration by an aldose reductase inhibitor. J. Neurochem. 71:775-783.

Lab Members

Post-doctoral fellow:

Naoya Yamashita, Ph.D

Graduate Students:

Chantal Bodkin-Clarke
Chih-Ming Chen
Jessica Houtz
Ami Patel
Emily Scott-Solomon

Undergraduate Students:

Muhammed Hamza