Rejji Kuruvilla is a professor of biology whose research focuses on the development and functions of the sympathetic nervous system. She received her BS from Calcutta University in India, her PhD from the University of Houston, and did her postdoctoral work at Johns Hopkins University School of Medicine.

Our laboratory studies the sympathetic nervous system, which is a key regulator of whole-body physiology in animals. The sympathetic nervous system is critical for triggering physiological responses to stress/danger and in maintaining body homeostasis under basal conditions. Sympathetic axons innervate diverse peripheral organs and tissues to control fundamental processes that affect our daily lives, including heart rate, body temperature, blood glucose levels, and immune function. We study sympathetic neurons because they serve as an excellent paradigm to understand how peripheral organs and tissues guide neuronal development, communication, and repair. We are also motivated by the growing awareness that sympathetic dysfunction underlies several pathologies including peripheral neuropathies, heart failure, hypertension, and diabetes. Our group has identified key molecular and cellular mechanisms by which peripheral organs instruct the development of sympathetic neurons through regulating neuron survival, axon growth, and target innervation. In recent work, we have addressed the contribution of sympathetic input to organ development and function by focusing on the pancreatic islets. Together, our studies of the sympathetic nervous system using mouse genetics, imaging, cellular, biochemical, and functional analyses provide new insights into the interplay between the nervous system and other organ systems.

a. Axonal transport of neurotrophin receptors regulates sympathetic neuron development and function

Ever since the pioneering studies of Rita Levi-Montalcini, Viktor Hamburger, and colleagues, neurobiologists have appreciated the importance of target tissues in neuronal development. Their work laid the foundation for a central tenet in developmental neuroscience, the ‘neurotrophic factor hypothesis’, that postulates that neurons are over-produced during development, and compete for limiting amounts of target-derived factors to grow, survive, and innervate target tissues. To date, the neurotrophin, nerve growth factor (NGF), is the best characterized target-derived instructive cue for sympathetic neuron development. As NGF is released by neuronal targets, a key cell biological problem is to understand how a signal impinging on axon terminals is relayed to trigger cellular responses necessary for neuronal development. We found that NGF signaling is communicated via vesicular transport of internalized NGF:TrkA receptor complexes in sympathetic neurons (Scott-Solomon et al., 2021). We have identified key mechanisms of NGF receptor endocytosis and axonal transport in sympathetic neurons. For example, we found that TrkA endocytosis in axons relies on the calcium-responsive phosphatase, calcineurin, and dephosphorylation of neuron-specific splicing isoforms of

dynamin1 (Bodmer et al., 2011). This finding led us to identify a role for dysregulated TrkA trafficking in Down syndrome, caused by trisomy of human chromosome 21. One of the genes that is triplicated in Down syndrome is Regulator of Calcineurin1 (RCAN1), an endogenous inhibitor of calcineurin. In a mouse model of Down syndrome, we observed impaired TrkA trafficking, loss of sympathetic neurons, and reduced innervation of targets, all of which could be alleviated by genetically reducing RCAN1 levels (Patel et al., 2015).

Neuronal responsiveness to target-derived factors also requires the precise axonal targeting of new receptors, synthesized in cell bodies. We discovered that TrkA receptors are delivered to sympathetic axons by a non-canonical transport mechanism called transcytosis (Ascano et al., 2009; Yamashita et al., 2017). Transcytosis is an atypical endocytosis-based mechanism, where newly synthesized proteins are first inserted on soma surfaces, internalized, and recycled long-distance to axons. Remarkably, transcytosis of TrkA receptors is regulated by NGF itself acting on axons, suggesting a positive feedback mechanism to scale up receptor availability in axons at times of need.

Current studies: We are using live imaging, confocal and electron microcopy, and cell biological/biochemical analyses to monitor the dynamic behavior and transport kinetics of receptor transcytosis, uncover the identity of the organelles responsible for TrkA transcytosis, and underlying regulatory mechanisms. An attractive hypothesis is that transcytosis is a more general mechanism than currently appreciated for the axonal delivery of pre-synaptic membrane proteins. We are testing this hypothesis using a biotinylation-based proteomic screen.

b. Sympathetic innervation promotes pancreatic islet maturation

The past decade has seen an exponentially growing interest in the sympathetic nervous system from the broader perspective of understanding how neural innervation affects target organ development and function. We have chosen to address this question by focusing on pancreatic islets, the functional units responsible for maintaining blood glucose levels. Islets are richly innervated by sympathetic nerves, and sympathetic input is known to modulate islet hormone release and influence glucose homeostasis in adult life (Lin et al., 2021). However, the developmental role(s) of innervation is far less defined. We provided the first evidence that early loss of sympathetic nerves disrupts islet morphology in neonatal mice and results in reduced insulin secretion and impaired glucose tolerance in adults (Borden et al., 2013).

Current studies: We are investigating anatomical, cellular, and functional interactions between sympathetic nerves and pancreatic cells using high resolution imaging, genomic and biochemical approaches, and genetic mouse models. To gain an unbiased view of islet transcriptional changes induced by de-innervation, we are using single-cell RNA sequencing. Viral tracing and transcriptional profiling allow us to map the neural circuits that regulate islet function and characterize the molecular identity of pancreas-projecting sympathetic neurons. We are also exploring a role for nerve-derived Neuropeptide Y (NPY) in islet organization and functional maturation. Such studies will provide critical information about the impact of sympathetic input on islet health and, potentially, lead to neuromodulation-based strategies for treatment of diabetes.

c. Satellite glial cells influence the activity of sympathetic neurons

Satellite glia are the major glial cell type present in the ganglia of the peripheral nervous system, where they envelop neuronal cell bodies. Despite this intimate association and emerging evidence implicating these cells in chronic pain and cardiac dysfunction, sateliite glial cells are one of the least understood cell types in the nervous system. Using single cell RNA sequencing and fluorescence in situ hybridization, we showed that satellite glia in sympathetic and sensory ganglia are remarkably diverse and transcriptionally tuned to accommodate the functions of associated neurons. Our genetic ablation studies in mice revealed that satellite glia play a key role in modulating the activity of sympathetic neurons (Mapps et al., 2022a). Mice lacking these glia exhibit enhanced sympathetic neurotransmission and perturbed autonomic responses such as elevated heart rate. This unexpected finding brings a new perspective to the basis of sympathetic hyperactivity in disorders such as cardiovascular disease and hypertension.

Current studies: Through single cell RNA-seq, we identified 4 distinct satellite glial populations in sympathetic ganglia and defined unique gene signatures for each population (Mapps et al., 2022b). We are thus poised to target individual satellite glial cell sub-types genetically for imaging and ablation studies. We are addressing how specific sub-types are specified during development, how they become intimately associated with their neuronal neighbors, and how glia-neuron interactions influence the formation, function, and maintenance of sympathetic circuits.

Kumari R, Boehm E, Pascalau R, Pfeiffer RL, Jones BW, Tampakakis E, Kuruvilla R. Retrograde control of sympathetic neuron-satellite glia interactions by target-derived NGF signaling. Cell Rep. 2025 Dec 12;44(12):116697.

Meriau P, Kuruvilla R, Cavalli V. Satellite glial cells: Shaping peripheral input into the brain-body axis? Neuron. 2025 Oct 15;113(20):3333-3351.

Chen X, Lin E, Haghightatian MM, Shepard LW, Hatter S, Kuruvilla R, Zhao H. Light modulates glucose and lipid homeostasis via the sympathetic nervous system. Sci Adv. 2024 Dec 11;10(50):eadp3284.

Kumari R, Pascalau R, Wang H, Bajpayi S, Yurgel M, Quansah K, Hattar S, Tampakakis E, Kuruvilla R. Sympathetic NPY controls glucose homeostasis, cold tolerance, and cardiovascular functions in mice. Cell Rep. 2024 Feb 27;43(2):113674.

Connor BM, Moya-Alvarado G, Yamashita Y, Kuruvilla R. Transcytosis-mediated anterograde transport of TrkA receptors is necessary for sympathetic neuron development and function. PNAS. 2023 Feb 7;120(6):e2205426120.

Mapps AA, Boehm E, Beier C, Keenan WT, Langel J, Liu M, Thomsen MB, Hattar S, Zhao H, Tampakakis E, Kuruvilla R. Satellite glia modulate sympathetic neuron survival, activity, and autonomic function. Elife. 2022 Aug 23;11:e74295.

Mapps AA, Thomsen MB, Boehm E, Zhao H, Hattar S, Kuruvilla R. Diversity of satellite glia in sympathetic and sensory ganglia. Cell Rep. 2022 Feb 1;38(5):110328.

Scott-Solomon E, Boehm E, Kuruvilla R. The sympathetic nervous system in development and disease. Nat Rev Neurosci. 2021 Nov;22(11):685-702.

Lin EE, Scott-Solomon E, Kuruvilla R. Peripheral Innervation in the Regulation of Glucose Homeostasis. Trends Neurosci. 2021 Mar;44(3):189-202.

Pascalau R, Kuruvilla R. A Hairy End to a Chilling Event. Cell. 2020 Aug 6;182(3):539-541.

Douglass SM, Fane ME, Sanseviero E, Ecker BL, Kugel CH 3rd, Behera R, Kumar V, Tcyganov EN, Yin X, Liu Q, Chhabra Y, Alicea GM, Kuruvilla R, Gabrilovich DI, Weeraratna AT. Myeloid-Derived Suppressor Cells Are a Major Source of Wnt5A in the Melanoma Microenvironment and Depend on Wnt5A for Full Suppressive Activity. Cancer Res. 2021 Feb 1;81(3):658-670.

Avraham O, Deng PY, Jones S, Kuruvilla R, Semenkovich CF, Klyachko VA, Cavalli V. Satellite glial cells promote regenerative growth in sensory neurons. Nat Commun. 2020 Sep 29;11(1):4891.

Scott-Solomon E, Kuruvilla R. Prenylation of Axonally Translated Rac1 Controls NGF-Dependent Axon Growth. Dev Cell. 2020 Jun 22;53(6):691-705.e7.

Kuruvilla R. Why brown fat has a lot of nerve. Nature. 2019 May;569(7755):196-197.

Ceasrine AM, Ruiz-Otero N, Lin EE, Lumelsky DN, Boehm ED, Kuruvilla R. Tamoxifen Improves Glucose Tolerance in a Delivery-, Sex-, and Strain-Dependent Manner in Mice. Endocrinology. 2019 Apr 1;160(4):782-790.

Crerar H, Scott-Solomon E, Bodkin-Clarke C, Andreassi C, Hazbon M, Logie E, Cano-Jaimez M, Gaspari M, Kuruvilla R, Riccio A. Regulation of NGF Signaling by an Axonal Untranslated mRNA. Neuron. 2019 May 8;102(3):553-563.e8.

Ceasrine AM, Lin EE, Lumelsky DN, Iyer R, Kuruvilla R. Adrb2 controls glucose homeostasis by developmental regulation of pancreatic islet vasculature. Elife. 2018 Oct 10;7:e39689.

Yamashita N, Joshi R, Zhang S, Zhang ZY, Kuruvilla R. Phospho-Regulation of Soma-to-Axon Transcytosis of Neurotrophin Receptors. Dev Cell. 2017 Sep 25;42(6):626-639.e5.

Chen CM, Orefice LL, Chiu SL, LeGates TA, Hattar S, Huganir RL, Zhao H, Xu B, Kuruvilla R. Wnt5a is essential for hippocampal dendritic maintenance and spatial learning and memory in adult mice. PNAS. 2017 Jan 24;114(4):E619-E628.

Houtz J, Borden P, Ceasrine A, Minichiello L, Kuruvilla R. Neurotrophin Signaling Is Required for Glucose-Induced Insulin Secretion. Dev Cell. 2016 Nov 7;39(3):329-345.

Yamashita N, Kuruvilla R. Neurotrophin signaling endosomes: biogenesis, regulation, and functions. Curr Opin Neurobiol. 2016 Aug;39:139-45.

Patel A, Yamashita N, Ascaño M, Bodmer D, Boehm E, Bodkin-Clarke C, Ryu YK, Kuruvilla R. RCAN1 links impaired neurotrophin trafficking to aberrant development of the sympathetic nervous system in Down syndrome. Nat Commun. 2015 Dec 14;6:10119.

Wang G, Rajpurohit SK, Delaspre F, Walker SL, White DT, Ceasrine A, Kuruvilla R, Li RJ, Shim JS, Liu JO, Parsons MJ, Mumm JS. First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic β-cell mass. 2015. Elife. Jul 28;4:e08261.

Houtz J, Kuruvilla R. VIP pipes up: neuronal signals direct tubulogenesis. Dev Cell. 2014 Aug 25;30(4):361-2.

Borden P, Houtz J, Leach SD, Kuruvilla R. Sympathetic innervation during development is necessary for pancreatic islet architecture and functional maturation. Cell Rep. 2013 Jul 25;4(2):287-301.

Chen SK, Chew KS, McNeill DS, Keeley PW, Ecker JL, Mao BQ, Pahlberg J, Kim B, Lee SC, Fox MA, Guido W, Wong KY, Sampath AP, Reese BE, Kuruvilla R, Hattar S. Apoptosis regulates ipRGC spacing necessary for rods and cones to drive circadian photoentrainment. Neuron. 2013 Feb 6;77(3):503-15.

Ryu YK, Collins SE, Ho HY, Zhao H, Kuruvilla R. An autocrine Wnt5a-Ror signaling loop mediates sympathetic target innervation. Dev Biol. 2013 May 1;377(1):79-89.

Lazo OM, Gonzalez A, Ascaño M, Kuruvilla R, Couve A, Bronfman FC. BDNF regulates Rab11-mediated recycling endosome dynamics to induce dendritic branching. J Neurosci. 2013 Apr 3;33(14):6112-22.

Ho HY, Susman MW, Bikoff JB, Ryu YK, Jonas AM, Hu L, Kuruvilla R, Greenberg ME. Wnt5a-Ror-Dishevelled signaling constitutes a core developmental pathway that controls tissue morphogenesis. PNAS. 2012 Mar 13;109(11):4044-51.

Ascano M, Bodmer D, Kuruvilla R. Endocytic trafficking of neurotrophins in neural development. Trends Cell Biol. 2012 May;22(5):266-73.

Bodmer D, Ascaño M, Kuruvilla R. Isoform-specific dephosphorylation of dynamin1 by calcineurin couples neurotrophin receptor endocytosis to axonal growth. Neuron. 2011 Jun 23;70(6):1085-99.

Armstrong A, Ryu YK, Chieco D, Kuruvilla R. Frizzled3 is required for neurogenesis and target innervation during sympathetic nervous system development. J Neurosci. 2011 Feb 16;31(7):2371-81.

Ascaño M, Richmond A, Borden P, Kuruvilla R. Axonal targeting of Trk receptors via transcytosis regulates sensitivity to neurotrophin responses. J Neurosci. 2009 Sep 16;29(37):11674-85.

Bodmer D, Levine-Wilkinson S, Richmond A, Hirsh S, Kuruvilla R. Wnt5a mediates nerve growth factor-dependent axonal branching and growth in developing sympathetic neurons. J Neurosci. 2009 Jun 10;29(23):7569-81.

Zweifel LS, Kuruvilla R, Ginty DD. Functions and mechanisms of retrograde neurotrophin signalling. Nat Rev Neurosci. 2005 Aug;6(8):615-25.

Valdez G, Akmentin W, Philippidou P, Kuruvilla R, Ginty DD, Halegoua S. Pincher-mediated macroendocytosis underlies retrograde signaling by neurotrophin receptors. J Neurosci. 2005 May 25;25(21):5236-47.

Chen X, Ye H, Kuruvilla R, Ramanan N, Scangos KW, Zhang C, Johnson NM, England PM, Shokat KM, Ginty DD. A chemical-genetic approach to studying neurotrophin signaling. Neuron. 2005 Apr 7;46(1):13-21.

Kuruvilla R, Zweifel LS, Glebova NO, Lonze BE, Valdez G, Ye H, Ginty DD. A neurotrophin signaling cascade coordinates sympathetic neuron development through differential control of TrkA trafficking and retrograde signaling. Cell. 2004 Jul 23;118(2):243-55.

Ye H, Kuruvilla R, Zweifel LS, Ginty DD. Evidence in support of signaling endosome-based retrograde survival of sympathetic neurons. Neuron. 2003 Jul 3;39(1):57-68.

Kuruvilla R, Ye H, Ginty DD. Spatially and functionally distinct roles of the PI3-K effector pathway during NGF signaling in sympathetic neurons. Neuron. 2000 Sep;27(3):499-512.

Research Scientists 

Guillermo Moya Alverado

Postdoctoral Fellows

Raniki Kumari

Riya Paul

Graduate Students

Jieying Li

Undergraduate Students

Kay Leen Soh

Anargya Ramamoorthy

Reynard Wongso

Hannah Kagan

Alumni