Current Projects In the Lab
There are several projects that are available which will be scaled for undergrad students, grad students, or post-docs. Without getting bogged down with too much detail, here are a few potential projects available for people to work on. Of course these will evolve as we move forward.
1. Examine neuronal competition for survival in complex populations of neurons.
Our previous work exploited the relative simplicity of the sympathetic nervous system to delineate the rules for competition. Other populations of neurons, such as those in the dorsal root ganglia, are more complex. We hypothesize that in these more complex systems the sensitization process is likely to remain very similar to what we observe in the sympathetic nervous system. Punishment signaling may function differently however, as the punishment cues identified in sympathetic neurons — BDNF-induced p75 signaling for instance — would actually have trophic effects in some neighboring TrkB positive neurons.
2. Delineate signaling underlying protection and punishment cross-talk
This has been a long-standing issue in the trophic factor field, however very little is known. We have developed several promising leads as to how these signaling pathways communicate with one another. Understanding how these antagonistic programs communicate with each other not only has implications for the development of the nervous system, but may also lead to insights into pathologies such as neuroblastoma or neurodegeneration.
3. Examine if signaling programs involved in competition for survival are also involved in competition for synaptic connectivity
After a developmental critical period, neurons no longer rely on target derived trophic factor for survival even though its availability and signaling persist into adulthood. If this signaling is not functioning as a pro-survival cue, what is it doing after this critical period? Synapse formation is an attractive candidate for this since it occurs after competition for survival. Therefore, this project will center around determining whether this signaling is important for synapse formation.
4. Examine the role of novel target derived neurotrophin regulated genes in developmental processes such as competition, axon extension, axon branching, changes in metabolism, and acquisition of neurotransmitter phenotype.
We previously performed a microarray analysis to identify genes regulated by target derived trophic factor in vivo. There are still 100's of interesting genes yet to be characterized in these processes. We have already begun characterizing genes that are important for cytoskeletal re-arrangement, signaling endosome function, and axon guidance.
5. Determine if re-engagement of developmental competition programs can participate in diseases of the nervous system.
The notion of pathologies co-opting developmental programs has been proposed in certain types of cancer as well as in complications in nerve regeneration. While there has been significant progress made identifying causative factors underlying neurodegenerative pathologies, the mechanism by which the pathology spreads to asymptomatic neurons in diseases such as Parkinson’s or ALS has been largely unexplored.
Vaccari, A., ^Gamage, K.K., #Nachum, S., Condron, B., Deppmann C.D., Acton, S.T., Image Analysis for Automated Assessment of Axon Degeneration. Asilomar Conf. on Signals, Systems and Computers. (Invited paper) In Press
Blasier, K.R., Mitchell, D.J., Ross,M.W., Smiley,W.R., ^Suo, D., #Park, J., Pullikuth, A.K., Catling, A.D., Deppmann, C.D., Pfister, K.K. Recruitment of dynein to endosomes for retrograde survival signal transport requires specific phosphorylation of the dynein intermediate chain by a Trk/ERK pathway. J. Neuroscience (2012) 32(44):15495-510
*^Kodis, E., *^Smindek, R., *^Kefauver, J., *Heffner, D., ^Aschenbach, K., Brennan, E., #Chan, K., ^Gamage, K.K., #Lambeth, P., Lawler, J., ^Sikora, A., #Vercroysse, N., +Deppmann C.D. First Messengers. Encyclopedia of Life Sciences. (2012)
*Sharma, N., *Deppmann, C.D., *Harrington, A.W., St. Hillaire C., Chen, Z.Y., Lee, F.S., Ginty D.D. (2010) Long distance control of synapse assembly by target-derived NGF. Neuron. 67(3): 422-34
+Deppmann, C.D., and +Janes K. Cytokine-cytokine crosstalk and cell-death decisions. Systems Biology of Apopotosis. Springer publishers. Systems Biology of Apoptosis (2012): 163-180.
*Deppmann, C.D., *Mihalas, S., *Sharma, N., Lonze, B.E., Niebur, E, Ginty D.D. (2008) A Model for Neuronal Competition During Development. Science, 320(5874) 369-73.
Deppmann, C.D., Ginty D.D. (2006) Retrograde Control of Neural Circuit Formation. Cell 127(7) 1307-7.
+ Corresponding Author *equal contribution
#UVA Undergrad Student ^UVA Grad student