Karin Löw, Ph.D.
Assistant Project Scientist

Current Research

My research focuses on gene therapeutic approaches to modulate the internal growth state of adult central nervous system (CNS) neurons to promote axon regeneration after spinal cord injury.

Axons of adult CNS neurons do not spontaneously regenerate, whereas neurons readily grow axons during nervous system development. This is due in part to the altered expression pattern of growth promoting and inhibiting cues in the adult CNS environment as well as the altered expression pattern of axonal receptors interpreting these environmental cues. Axonal re-growth can also be observed in the adult CNS under certain circumstances. For example, proprioceptive sensory axons in the spinal cord show some regenerative capacity after a sciatic nerve pre-conditioning lesion and the concomitant alterations in gene expression in the dorsal root ganglion (DRG).

In a first step we therefore identified potential regeneration-promoting therapeutic genes by differential gene expression analyses in the above paradigms. Identified gene candidates comprise axonal receptors as well as transcription factors that might represent master control regulators of regeneration programs.

Candidate genes are evaluated for their axonal growth-promoting potential in neuronal cultures in vitro as well as in vivo after spinal cord injury. To this end, candidate genes are incorporated into dual-promoter lentiviral vectors expressing both the therapeutic gene and an axonal tracer. Recombinant lentiviruses are used to infect DRG neurons as well as CNS neurons with descending projections to the spinal cord (e.g. corticospinal and rubrospinal neurons) to over-express "regeneration associated" genes. Regenerative responses can be evaluated in "treated axons" identified by expression of the axonal tracer in the spinal cord lesion site.


Recent Publications:

Löw K, Culbertson M, Bradke F, Tessier-Lavigne M and Tuszynski M. Netrin-1 is a Novel Myelin-Associated Inhibitor to Axon Growth. Manuscript in revision, Journal of Neuroscience (2007).

Löw K, Crestani F, Keist R, Benke D, Brunig I, Benson JA, Fritschy JM, Rulicke T, Bluethmann H, Mohler H, and Rudolph U. Molecular and neuronal substrate for the selective attenuation of anxiety. Science (2000): 290, 131-4.

Löw K, Orberger G, Schmitz B, Martini R and Schachner M. The L2/HNK-1 carbohydrate is carried by the myelin associated glycoprotein and sulphated glucuronyl glycolipids in muscle but not cutaneous nerves of adult mice. European Journal of Neuroscence (1994): 6, 1773-1781.