Hi! I’m Joshua Sampson. I’m studying Biomedical Engineering at the University of Michigan in Ann Arbor. I work in the lab of Dr. Lonnie Shea, PhD, under the wonderful mentorship of Richard Youngblood. We are developing a 3D biopolymer scaffold for differentiation of pluripotent stem cells into pancreatic islet cells and subsequent transplantation to treat type 1 diabetes. I’ve also worked on lymphedema treatment for the amazingly kind Dr. Stan Rockson, MD, who has accomplished much for lymphedema patients, including his own at Stanford Medicine, and on heart failure for the dedicated R&D team at Ancora Heart, a medical device startup in Santa Clara, CA.

This summer, I’m performing research under the convivial mentorship of Cameron Pernia in the lab of Dr. Evan Snyder, MD, PhD, at the Sanford Consortium for Regenerative Medicine in La Jolla, CA. The Snyder lab is interested in using stem cells for understanding neurological development, modeling neurological disease, and therapeutic transplant.

Alzheimer’s disease affects 5.7 million Americans, robbing their memory, cognition, and ultimately, their life. You probably have a loved one or know someone with a loved one affected by Alzheimer’s disease. I am studying this neurodegenerative disease using induced pluripotent stem cell technology to create neurons from skin cells harmlessly donated by patients.

By watching the fluctuation of calcium ions (the same calcium you get from drinking milk!) in these neurons, I can study how network behavior of Alzheimer’s disease neurons differs from that of healthy controls. The differences may be a missing link for how cognitive symptoms can emerge from changes down at the protein level.

There at the protein level, modifications of CRMP2 appear conspicuous. CRMP2 both modulates calcium ion flux and stabilizes the fine neuronal structure that begets signaling connections. It facilitates pathogenesis from beta amyloid, the hallmark protein of Alzheimer’s disease. Moreover, a presumably unhealthy level of modified (“hyperphosphorylated”) CRMP2 has been observed in the “tangles” characteristic of Alzheimer’s disease. I will quantify modifications to CRMP2 in the neurons, and examine the implications.

Ultimately, we care about therapeutics to help patients. I am investigating the effect in the neurons of lithium salts, which have stalled cognitive decline in clinical studies of Alzheimer’s disease. Lithium modulates both CRMP2 regulation and calcium ion flux, so I will again examine those features. Deciphering lithium’s action will expose the pathobiology of Alzheimer’s disease, and suggest improved therapeutic pathways.

Together, by studying calcium ion flux, CRMP2 regulation, and lithium’s mechanisms of action in skin cell-derived neurons, I will inform protein- to neuronal network-level pathologies of Alzheimer’s disease. These insights will hopefully uncover therapeutic avenues to ultimately improve Alzheimer’s patients lives.