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Zachary P. Wills

  • Assistant Professor

Neural circuit development and dysfunction in disease.

A major focus of our lab is to understand how the development of neuronal circuits is orchestrated in the brain to enable the execution of complex tasks like learning and memory and how failures in this process contribute to disease.

Our work has uncovered novel mechanisms that function to restrict synapse and circuit development in the hippocampus. The focus of our research is to uncover the molecular mechanisms that underlie synaptic restriction using high-resolution live imaging of an intact circuit. In combination with molecular and biochemical approaches, we aim to define what are the molecular mediators controlling this process and how they function to restrict synaptic development.

This work may have direct relevance for several human neurological diseases since several of the factors we have identified may contribute to neurological conditions such as Alzheimer’s disease and Schizophrenia. We study mouse models for both these diseases and aim to uncover what role molecules involved in the establishment of hippocampal circuitry play in brain dysfunction resulting from these devastating neurological conditions.

Representative Publications

RNA Binding Antagonizes Neurotoxic Phase Transitions of TDP-43.
Mann, J. R., Gleixner, A. M., Mauna, J. C., Gomes, E., DeChellis-Marks, M. R., Needham, P. G., Katie E. Copley, Bryan Hurtle, Bede Portz, Pyles, N. J., Guo, L., Calder, C. B., Wills, Z. P., Pandey, U. B., Kofler, J. K., Brodsky, J. L., Thathiah, A., Shorter, J. Donnelly, C. J.
 
Excitatory Dendritic Mitochondrial Calcium Toxicity: Implications for Parkinson’s and Other Neurodegenerative Diseases.
Verma, M., Wills, Z.P., & Chu, C. T. (2018).
 
Abnormal dendritic calcium activity and synaptic depotentiation occur early in a mouse model of Alzheimer's disease.
Bai Y, Li M, Zhou Y, Ma L, Qiao Q, Hu W, Li W, Wills ZP, Gan WB
 
Amyloid Beta Peptides Block New Synapse Assembly by Nogo Receptor Mediated Inhibition of T-Type Calcium Channels.
Zhao Y, Sivaji S, Chaing MC, Ali H, Zukowski M., Ali S, Kennedy B., Sklyar, A., Cheng A. Guo Z., Reed A., Kodali R, Borowski J., Frost G, Beukema P, Wills ZP
 
Selective Loss of Smaller Spines in Schizophrenia.
MacDonald ML, Alhassan J, Newman JT, Richard M, Gu H, Kelly RM, Sampson AR, Fish KN, Penzes P, Wills ZP, Lewis DA, Sweet RA
 
Developmental pruning of excitatory synaptic inputs to parvalbumin interneurons in monkey prefrontal cortex.
Chung DW, Wills ZP, Fish KN, Lewis DA
 
The Nogo Receptor Family Restricts Synapse Number in the Developing Hippocampus.
Wills, Z.P., Mandel-Brehm, C., Mardinly, A.R., McCord, A.E., Giger, R.J., Greenberg, M.E.
 
Cyclin E Constrains Cdk5 Activity to Regulate Synaptic Plasticity and Memory Formation
Odajima, J. 1, Wills, Z.P., 1 Ndassa, Y.M., Terunuma, M., Kretschmannova, K., Deeb, T.Z., Geng, Y., Gawrzak, S., Quadros, I.M., Newman, J., Das, M., Jecrois, M.E., Yu, Q., Li, N., Bienvenu, F., Moss, S.J., Greenberg, M.E., Marto, J.A., Sicinski, P.