Research Faculty

Address
630 W 168th Street
Black Bldg. 1210A
New York, NY 10032

Phone: 212-305-9334
Fax: 646-426-0059

uh2112@cumc.columbia.edu
Education and Training
Ph.D., University of Basel, 2003

Affiliations
Integrated Program
MD-PhD Program
Neurobiology & Behavior
Pathobiology
Taub Institute
Affiliations
Taub Institute

Collaborations
At Columbia: C. Troy, P. Nagy, J. Crary

Intl Collaborations
Ramiro Almeida, PhD
University of Coimbra, Portugal
Andreia Battista, Vitor Pinto, PhD, Hugo Almeida, PhD University of Minho, Portugal

Ulrich Hengst, Ph.D
Assistant Professor of Pathology and Cell Biology (in the Taub Institute)
Research Summary

Work in our laboratory focuses on the role of intra-axonal mRNA translation in development and neurodegenerative disorders.

Traditionally, protein synthesis has been considered to occur exclusively in the cell body, but in highly polarized cells such as neurons some mRNAs are selectively transported to the periphery. Over the last couple of years, several axonal mRNAs as well as stimuli that trigger their translation have been described: the guidance cue Semphorin3A causes growth cone collapse in sensory neurons by triggering the local synthesis of RhoA; the mRNA for the transcription factor CREB is locally translated in response to NGF, and CREB then translocates to the nucleus and supports neuronal survival. We also found that netrin-1 and NGF trigger axonal elongation via the local translation of Par3, a key component of the PAR polarity complex. Despite increasing evidence for the existence of local translation in many questions remain unanswered: What is the in vivo relevance of local translation? Why are some proteins locally translated? What is the role of local translation in neurodegenerative disorders?

In order to address these questions we are currently working on several closely related projects:

Local protein synthesis and neurodegeneration. Intra-axonal mRNA translation is necessary for axon development and regeneration. Additionally, various neurodegenerative disorders are linked to axonally localized mRNAs, axon transport or potentially the intra-axonal protein translation machinery. We are studying the relevance of axonal protein synthesis for neurodegeneration on the example of Alzheimer’s disease. We have identified mRNAs that are axonally recruited and locally translated in response a neurodegenerative stimulus, oligomeric beta-amyloid. In several projects we are investigating the role of these mRNAs in the pathogenesis of Alzheimer’s disease using both in vitro and in vivo approaches.

Integration of signaling pathways through local translation. During the development of the central nervous system many seemingly separate pathways govern different aspects of axon growth and pathfinding. Several of these pathways are at least partially regulated through local translation of rate-limiting proteins. We are hypothesizing that local translation can serve to ensure temporal and spatial coincidence in the activation of signaling pathways that control different aspects of axonal development. We are employing cell biological and molecular biological approaches to characterize the mechanisms of the coordinated translational activation of specific sets of localized mRNAs.
Service Activities

Member - Doctoral Program in Neurobiology and Behavior Admissions Committee (2012 – present)

Selected Publications

1. Walker, B.A., Hengst, U., Kim, H.J., Jeon, N.L., Schmidt, E.F., Heintz, N., Milner, T.A., and Jaffrey, S.R. (2012). Reprogramming axonal behavior by axon-specific viral transduction. Gene Ther. 19, 947-955.

2. Hengst, U., Deglincerti, A., Kim, H.J., Jeon, N.L., and Jaffrey, S.R. (2009). Axonal elongation triggered by stimulus-induced local translation of a polarity complex protein. Nat. Cell Biol. 11, 1024-1030.

3. Cox, L.J., Hengst, U., Gurskaya, N.G., Lukyanov, K.A., and Jaffrey, S.R. (2008). Intra-axonal translation and retrograde trafficking of CREB promotes neuronal survival. Nat. Cell Biol. 10, 149-159.

4. Hengst, U., and Jaffrey, S.R. (2007). Function and translational regulation of mRNA in developing axons. Semin. Cell Dev. Biol. 18, 209-215.

5. Wu, K.Y., Zippin, J.H., Huron, D.R., Kamenetsky, M., Hengst, U., Buck, J., Levin, L.R., and Jaffrey, S.R. (2006). Soluble adenylyl cyclase is required for netrin-1 signaling in nerve growth cones. Nat. Neurosci. 9, 1257-1264.

6. Hengst, U., Cox, L.J., Macosko, E.Z., and Jaffrey, S.R. (2006). Functional and selective RNA interference in developing axons and growth cones. J. Neurosci. 26, 5727-5732.

7. Wu, K.Y.,Hengst, U., Cox, L.J., Macosko, E.Z., Jeromin, A., Urquhart, E.R., and Jaffrey, S.R. (2005). Local translation of RhoA regulates growth cone collapse. Nature 436, 1020-1024.

8. Kvajo, M., Albrecht, H., Meins, M., Hengst, U., Troncoso, E., Lefort, S., Kiss, J.Z., Petersen, C.C., and Monard, D. (2004). Regulation of brain proteolytic activity is necessary for the in vivo function of NMDA receptors. J. Neurosci. 24, 9734-9743.

9. Murer, V., Spetz, J.F.,Hengst, U., Altrogge, L.M., de Agostini, A., and Monard, D. (2001). Male fertility defects in mice lacking the serine protease inhibitor protease nexin-1. Proc. Natl. Acad. Sci. U. S. A. 98, 3029-3033.

10. Hengst, U., Albrecht, H., Hess, D., and Monard, D. (2001). The phosphatidylethanolamine-binding protein is the prototype of a novel family of serine protease inhibitors. J. Biol. Chem. 276, 535-540.

11. Hengst, U., and Kiefer, P. (2000). Domains of human respiratory syncytial virus P protein essential for homodimerization and for binding to N and NS1 protein. Virus Genes 20, 221-225.

Current Projects

R01 MH 096702-02 Hengst (PI) 04/01/2012 – 03/31/2017
NIH/NIMH
Intra-axonal signaling pathways triggered by attractive guidance cues.


Honors and Awards

1993 - 1998
Scholarship of the German National Academic Foundation (Studienstiftung des deutschen Volkes)

2006 - 2007
Postdoctoral Fellowship of the Paralysis Project of America

2007 - 2012
NIH Pathway to Independence Award (K99/R00)

2010 - 2012
New Investigator Award of the Alzheimer’s Association

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