REJJI KURUVILLA
Biology

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

The proper 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. Interest in understanding the biology of neurotrophins remains unabated due to their association with a wide spectrum of human diseases ranging from developmental disorders such as neuroblastoma and hereditary neuropathies, to psychiatric and neurological disorders in adults. We are employing molecular, cellular and genetic approaches to address fundamental aspects of neurotrophin signaling and function in neurons:

I. Regulation of neuronal development by trafficking of neurotrophins and their receptors: 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. Our long-term goal is to gain insight into how neurotrophins coordinate neuronal development by regulating the cell’s endocytic machinery. Using a combination of fluorescent, biochemical and electron microscopic assays, we are investigating molecular mechanisms of endocytosis, recycling and axonal transport of neurotrophins and their receptors in developing neurons. We are employing structure-function analyses to identify endocytic motifs in the neurotrophin receptors, the Trk receptor tyrosine kinases, that mediate distinct aspects of receptor trafficking. Finally, we are assessing the role of distinct modes of Trk trafficking on neurotrophin-dependent survival, axonal growth and neuronal morphology.

II. Identification of local and retrograde signaling mechanisms underlying neurotrophin-mediated axonal growth: A second project in the lab is focused on investigating the intracellular signaling pathways by which target-derived neurotrophins regulate multiple stages of axonal growth including axon initiation, projection along intermediate targets and innervation of final target tissues. We are employing in vitro and in vivo approaches to dissect the local signaling pathways activated in axon terminals, as well as transcriptional programs activated in remote neuronal soma by target-derived neurotrophins, that mediate unique aspects of axonal growth and morphology.

Representative Publications

Oscar Marcelo Lazo, Andres Gonzalez, Maria Ascano, Rejji Kuruvilla, Andres Couve, and Francisca Bronfman. BDNF regulates Rab11-mediated recycling endosome dynamics to induce dendritic branching. J. Neuroscience. In press.

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.