Hi everyone! My name is Daksh, and I am a rising junior here at Pitt pursuing a degree in Neuroscience, with a minor in Computer Science. Some of my favorite things to do outside of school include outdoor activities such as tennis/running, traveling, and learning new skills. Over the summer I will be continuing doing research with my mentor Dr. Zachary Wills. The main focus of our lab’s work is to try and uncover how neural circuit connections are orchestrated during development, and how failures in this process may contribute to disease.

To provide some more detail, the brain is composed of a multitude of neurons that make connections with one another at sites called synapses. The alteration of synapses through either addition or elimination has been found to contribute to long-term learning, but aberrant regulation of these connections is thought to contribute to neurodegenerative disease and intellectual disabilities such as schizophrenia and autism. A greater understanding of what molecular processes regulate this plasticity of synaptic connections is imperative for designing treatments for such diseases.

Our lab focuses on the activity of a key family of genes involved in restricting synaptogenesis (or synapse assembly) called the Nogo receptors (NgRs). We have found that an intracellular protein named RhoA contributes to NgR’s synaptic effects by ultimately blocking calcium currents. The image below depicts the proposed molecular processes regulating the stabilization and loss of synaptic connections (the arrows represent activation, and the T-arrows represent inhibition).

Conversely, a key mediator of synaptogenesis is Brain-Derived Neurotrophic Factor (BDNF), which has been found to work through the activation of cAMP and PKA. Our lab has found that BDNF exposure, and subsequent PKA activation reduces RhoA activity, but we do not know how this occurs. We hypothesize that PKA inhibits RhoA activity by phosphorylating it at a specific residue, and this is what I will be seeking to answer over the summer. I will be answering this question by obtaining neuronal slice cultures from mice and performing live imaging and analyzing the sites of synaptic connections through software.

My current career goals are to attend medical school and obtain either an M.D. or M.D/PhD. I’ve developed a strong appreciation and curiosity for how the brain functions over the past few years and am passionate about working to broaden our understanding of this functioning through research in order to help individuals suffering from neurological conditions. This fellowship will allow me to dedicate my time this summer to performing this research and will also allow me to learn about other student’s research projects as well as other aspects of the research world.