Peter Nicholls

Background

About Peter Nicholls

In 2003, as a psychiatry resident at Duke, I began working with the posttraumatic stress disorder researcher Jonathan Davidson. We published two papers together based on clinical data; but during this time I started to wonder about the biological underpinnings of PTSD. I therefore began training in William Wetsel’s Mouse Behavioral and Neuroendocrine Lab and eventually completed the coursework for a Masters in Medical Genomics, while also serving as a chief resident in psychiatry. Since graduating from Duke’s psychiatry residency in 2006, I have worked full-time in basic research. After spending the first years generating mice deficient in various microRNAs using an innovative approach related to antisense oligonucleotides, I was awarded an R21 to investigate another mouse model I had designed: a transgenic mouse expressing a very sensitive and specific fluorescent marker of caspase activity. During this time, I worked in the labs of Marc Caron (cell biology), Nicole Calakos (electrophysiology), and Allan Johnson (imaging) in order to investigate caspase activity in the brains of stressed mice. Once I found a connection between caspase activity and behavioral stress, I started to study the effect of caspase inhibitors on behavior. From 2011 to 2018, an integral aspect of my work was multiphoton microscopy. In Dr. Johnson’s imaging lab, I had free access to a Zeiss multiphoton instrument 3 days a week; and I mastered various microscopy methods including tissue clarification, large-volume scans, and the imaging of dendritic spines. In the past several years, I have designed, generated, and been responsible for the husbandry and characterization of 4 lines of transgenic mice: VCre-dependent knockouts of the dopamine D2 and D4 receptors; a mouse with ubiquitous expression of VCre; and an inducible, conditional point mutation of Mef2d. Recently, I have designed and generated a system of 6 AAVs to test the dopamine hypothesis of schizophrenia, and designed and assembled a transgenic system for tracing 3-neuron circuits in mouse brain. Currently, I am preparing a manuscript, “Measuring nonapoptotic caspase activity with a transgenic reporter in mice,” describing the caspase activity reporter mouse; and I began in vitro characterization of my neural circuit tracing system. Since July 1, 2021, I have been working on gene therapy approaches for Alzheimer’s and Parkinson’s using viral vectors, human iPSC-derived organoids, and model mice in Duke’s Department of Neurology.