Pioneering Rehabilitation

Jian Zhong, Ph.D.

Director, Molecular Regeneration and Neuroimaging Laboratory

Center for Pain and Sensory Recovery

Associate Professor of Neuroscience
Brain and Mind Research Institute
Weill Cornell Medicine


(914) 368-3132

Research Focus

The primary focus of our laboratory is to delineate the molecular mechanisms that drive and direct axon growth, connectivity and regeneration in vivo

In mammalian embryos, axons grow vigorously and precisely to interconnect the nervous system, and form connections to sensory receptors, to muscles and to internal organs. In the mature nervous system, axon growth stops. After an injury, axons do regenerate (if imperfectly) in the peripheral nervous system, but no productive regeneration occurs in the central nervous system. Because of this lack of axon regeneration, spinal cord injuries, for example, result in permanent paralysis, and retinal axon degeneration in glaucoma causes irreversible loss of vision.

Two reasons have been suggested for why axons cannot re-grow in the mature CNS. First, cell-intrinsic growth pathways are downregulated as the nervous system matures, and second, the mature CNS expresses surface molecules that inhibit axon growth and thereby stabilize the mature configuration. Previous work has clearly shown that injured adult neurons in the CNS can in principle re-grow axons under certain circumstances. However, such axonal regrowth or sprouting have not been able to reach their targets due to limited length and density of regenerative growth. 

Our current major focus is to attempt driving axon regeneration in the injured optic nerve, which is a part of the CNS, by genetic activation in mature retinal neurons of pathways that we know can drive axon growth in embryonic neurons. We use several lines of genetically modified mice that allow us to selectively activate or inactivate specific signaling molecules in the nervous system shortly before nerve injury. We then assess regeneration phenotypes using high-resolution imaging, and we test for possible recovery of visual behaviors.

Additional current projects in our lab include the development of novel "transsynaptic tracer mice" that would enables us to visualize the entire network of neurons connected to an initial neuron or a population of neurons of interest, and to modulate gene activity in these neurons. This mouse model will be useful for a number of purposes, for example for the delineation of neuropathic pain circuitry, or to document axon regrowth and rewiring in a regeneration context.

Finally, we have developed several mouse models which mimic the neuronal aspects of human Neuro-Cardio-Facio-Cutaneous Syndromes (NCFCS). We plan to use these mice to devise and test possible therapeutic strategies targeting the very diverse symptoms associated with NCFCS.

In summary, our laboratory uses advanced genetically modified mouse models to dissect the signaling cascades directing axon growth, regeneration and neuronal functionality in vivo


Dr. Zhong received his Ph.D. (Dr. rer. nat) from the Ruhr University Bochum, Germany, in 1997.  He conducted postdoctoral research in the laboratories of Dr. Paul Patterson (Caltech, Pasadena, CA) and Dr. Bill Snider (University of North Carolina, Chapel Hill, NC). Dr. Zhong is an ad hoc reviewer for Nature Neuroscience, Neuron, Journal of Neuroscience, EMBO Reports and European Journal of Neuroscience as well as for the NIH "Neural Differentiation, Plasticity, Regeneration, and Rhythmicity (NDPR)" and "Cellular and Molecular Biology of Glia (CMBG)" study sections.


Karuppagounder SS, Alim I, Khim SJ, Bourassa MW, Sleiman SF, John R, Thinnes CC, Yeh TL, Demetriades M, Neitemeier S, Cruz D, Gazaryan I, Killilea DW, Morgenstern L, Xi G, Keep RF, Schallert T, Tappero RV, Zhong J, Cho S, Maxfield FR, Holman TR, Culmsee C, Fong GH, Su Y, Ming GL, Song H, Cave JW, Schofield CJ, Colbourne F, Coppola G, Ratan RR. (2016) Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models. Sci Transl Med. 8(328):328ra29. doi: 10.1126/scitranslmed.aac6008.

Zhong J. (2016) RAS and downstream RAF-MEK and PI3K-AKT signaling in neuronal development, function and dysfunction. Biol. Chem. 397: 215-222 ; PMID: 26760308

Huang S, O'Donovan KJ, Turner EE, Zhong J, Ginty DD. (2015) Extrinsic and intrinsic signals converge on the Runx1/CBFβ transcription factor for nonpeptidergic nociceptor maturation. Elife. 4:e10874.

Latremoliere A, Latini A, Andrews N, Cronin SJ, Fujita M, Gorska K, Hovius R, Romero C, Chuaiphichai S, Painter M, Miracca G, Babaniyi O, Remor AP, Duong K, Riva P, Barrett LB, Ferreirós N, Naylor A, Penninger JM, Tegeder I, Zhong J, Blagg J, Channon KM, Johnsson K, Costigan M, Woolf CJ. (2015) Reduction of Neuropathic and Inflammatory Pain through Inhibition of the Tetrahydrobiopterin Pathway. Neuron 86:1393-406.

Zhong J. (2015) RAFting the rapids of axon regeneration signaling. Neural Regen Res 10:341-3.

O’Donovan KJ, O’Keeffe C, Zhong J. (2014) Whole mount imaging of mouse embryo sensory axon projections. J Vis Exp (94). doi: 10.3791/52212

O’Donovan KJ, Ma K, Guo H, Wang C, Sun F, Han SB, Kim H, Wong J, Charron J, Zou H, Son Y-J, He Z, Zhong J. (2014) B-RAF kinase drives developmental axon growth and promotes axon regeneration in the injured mature CNS. J Exp Med 211:801-14. 
(Featured as a cover story and highlighted in an "Insights" article by V. Cavalli and D.M. Holtzman J Exp Med 211:746.) 

Zhong J, Zou H. (2014) BMP Signaling in Axon Regeneration. Curr Opin Neurobiol 27C:127-134.

Zhao Z, Huo F, Jeffry J, Hampton L, Demehri S, Kim S, Liu X, Barry DM, Wan L, Liu Z,  Li H, Turkoz A, Ma K, Cornelius LA, Kopan R, Battey JF Jr, Zhong J*, Chen Z* (*co-corresponding authors). (2013) Chronic itch development in sensory neurons requires BRAF signaling pathways. J Clin Invest 123:4769-4780.

Li X, Newbern JM, Wu Y, Morgan-Smith M, Zhong J, Charron J, Snider WD. (2012) MEK Is a Key Regulator of Gliogenesis in the Developing Brain. Neuron 75: 1035–1050.

Newbern JM, Li X, Shoemaker SE, Zhou J, Zhong J, Wu Y, Bonder D, Hollenback S, Coppola G, Geschwind DH, Landreth GE, Snider WD. (2011) Specific functions for ERK/MAPK signaling during PNS development. Neuron 69:91-105.

Newbern J, Zhong J, Wickramasinghe S, Li X, Wu Y, Samuels I, Cherosky N, Karlo J, O'Loughlin B, Wikenheiser J, Gargesha M, Doughman Y, Charron J, Ginty DD, Watanabe M, Saitta S, Snider WD, Landreth G. (2008) Mouse and human phenotypes indicate a critical conserved role for the ERK2 signaling pathway in neural crest development. Proc Natl Acad Sci USA 105:17115-20.

Zhong J, Li X, McNamee C, Chen A, Baccarini M, Snider WD. (2007) Raf kinase signaling functions in sensory neuron differentiation and axon growth in vivo. Nat Neurosci 10:598-607.
(Featured as a must-read paper by UCSD's The Signaling Gateway)

Zhong J, Pevny L, Snider WD. (2006) "Runx"ing towards sensory differentiation. Neuron 49(3), 325-7. 

Zhou FQ, Zhong J, Snider WD. (2003) Extracellular crosstalk: when GDNF meets N-CAM. Cell 113:814-5.

Markus A, Zhong J, Snider WD. (2002) Raf and Akt mediate distinct aspects of sensory axon growth. Neuron 35:65-76.

Snider WD, Zhou FQ, Zhong J, Markus A. (2002) Signaling the pathway to regeneration. Neuron 35:13-6.

Zhong J, Dietzel ID, Kopf M, Wahle P, Heumann R. (1999) Sensory Impairments and Delayed Regeneration of Sensory Axons in Interleukin-6-Deficient Mice. J Neurosci 19:4305-4313.

Current Projects

Identification of RAF Downstream Effectors that Drive Axon Growth
We have recently identified the B-RAF kinase signaling as a key player in embryonic axon growth signaling, and are testing B-RAF as a possible driver of regenerative growth. To identify the effectors that mediate B-RAF dependent growth, we mate B-RAF gain-of-function mice with mice carrying effector loss-of-function alleles, and analyze axon growth in the offspring.  To complement this approach, we also screen gene expression specifically induced or suppressed by B-RAF in nervous system tissues.

Development of a Novel Transsynatic Tracer Mouse Line
The reliable tracing of axonal connections is essential for any deeper understanding of nervous system function. Many tracing methods are available, but none allow reliable tracing beyond the second synaptic connection in vivo. We have designed a genetic strategy to enable multi-synaptic tracing of axonal connectivity in vivo, starting with any given neuron or neuron population of interest.

Mouse Models for Neuro-Cardio-Facio-Cutaneous Syndromes (NCFCS)
The NCFCS, which include Leopard Syndrome, Noonan Syndrome and Neurofibromatosis type I, are linked to loss- and gain-of function mutations in the RAF signaling pathway. We have observed phenotypes reminiscent of NCFCS in several of our mouse lines that carry RAF-related genetic manipulations. We are investigating and comparing these phenotypes in depth, and devising genetic strategies to counteract the NCFCS-like symptoms in vivo.

Lab Members

From left to right: Panos, Fra, Jian, Catherine, Caitlin, Mariel

Current Lab Members

Jian Zhong, Ph.D.
Jian Zhong, Ph.D.

Francesco Boato, Ph.D.
Francesco Boato, Ph.D.

Caitlin Malone
Caitlin Maloe, B.Sc.

Mariel Voutounou, Ph.D.
Mariel Voutounou, Ph.D.


Former Lab Members

Panagiotis Athanasopoulos
Panagiotis Athanasopoulos

Matthew Burrow

Hengchang Guo, Ph.D.

Andrew Katz

Kaijie Ma, BM

Kevin O’Donovan, Ph.D.

Catherine O'Keeffe
Catherine O'Keeffe


Wings for Life Foundation
PI: Jian Zhong
Title: Modulating cell-intrinsic growth signaling as a means to promote corticospinal tract axon regeneration
Dates: 06/2014 — 05/2017 

Craig H. Neilsen Foundation
PI: Jian Zhong
Title: A combinatory approach to elevating intrinsic growth capacity of CST axons
Dates: 06/2014 — 05/2017 

National Institutes of Health
1R01EY022409-01, National Eye Institute
PI: Jian Zhong
Title: B-RAF Drives Regenerative Axon Growth in the Optic Nerve in vivo
Dates: 05/2012 — 04/2017

National Institutes of Health
PI: Jian Zhong
Supplement to RO1

Whitehall Foundation
Three-year research grant, 2010-08-61
PI: Jian Zhong
Title: RAF Signaling in Sensory-Motor Circuit Formation
Dates: 08/2010 — 07/2013

Christopher & Dana Reeve Foundation
PI: Jian Zhong
Title: Enabling axon regeneration by turning the neurons back to their youth
Dates: 2012


April 2016
Wings for Life Research Foundation, Salzburg, Austria.

December 2015
16th International Symposium on Neural Regeneration, Asilomar, CA. (Francesco Boato, short talk)

December 2015
Oregon Health & Science University and Vollum Institute, Portland, OR.

September 2015
Invited Talk
Centre for Integrative Biology, University of Trento, Italy

September 2015
Invited Talk
Spinal Cord Injury Research Workshop, Italy

July 2015
Invited Talk
Shanghai Jiao Tong University, School of Medicine, Shanghai, China

June 2015
Francis Crick Symposium: Advances in Neuroscience, Suzhou, China

May 2015
Gotham Society for Mouse Development meeting. New York, Invited by Philippe Soriano. (presenter: Mariel Voutounou)

April 2015
Invited Talk
Neurosurgery Grand Rounds, Mount Sinai School of Medicine, New York

November 2014
Progress in Neuroscience seminar series, The Feil Family Brain and Mind Research Institute, Weill Cornell Medical College.

September 2014
International Conference of the GBM section “Molecular Neurobiology“, Bochum, Germany.

June 2014
Cold Spring Harbor Asia/NGF 2014, Suzhou, China.

May 2014
Joint Seminar of the Max Planck Institute of Molecular Physiology and Ruhr University International Graduate School of Neuroscience, Bochum, Germany.

October 2013
Shriners Hospitals Pediatric Research Center, Temple University School of Medicine.

July 2012
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiaotong University, School of Medicine.

July 2012
School of Life Science, Shanghai Tongji University.

July 2012
School of Medicine, Shanghai Tongji University.

June 2012
Symposium for Chinese Neuroscientists Worldwide 2012, Xi’an, China.

February 2011
Gotham Society for Mouse Development meeting. New York, Invited by Philippe Soriano. (presenter: Kevin O'Donovan)

January 2011
“Neuronal Mechanisms of Vision” Seminar, Ruhr University Bochum, Germany.