Paul Worley, M.D.

Research Education Component: Leader
E-mail: pworley@jhmi.edu

Dr. Worley’s research focuses on the molecular basis of learning and memory. He is examining biomarkers of molecular pathways essential for cognitive function that are altered in mild cognitive impairment and AD dementia. This includes NPTX2, which plays a central role in adaptive inhibitory circuit function, and mTORC1, a signaling complex that integrates multiple aspects of metabolism, energy homeostasis and growth factor signaling. The goal is to determine whether these brain proteins are altered early in the disease course and are related to symptom onset.

Publications

• Soldan A, Oh S, Ryu T, Pettigrew C, Zhu Y, Moghekar A, Xiao M-F, Pontone G, Albert M, Na C-H, Worley P. NPTX2 in cerebrospinal fluid predicts progression to mild cognitive impairment, Annals of Neurology, 2023; 94:620-631.
• Lin R, Learman LN, Na CH, Renuse S, Chen KT, Chen PY, Lee GH, Xiao B, Resnick SM, Troncoso JC, Szumlinski KK, Linden DJ, Park JM, Savonenko A, Pandey A, Worley PF Persistently elevated mTOR Complex 1-S6 Kinase 1 disrupts DARPP-32-Dependent D1 Dopamine receptor signaling and behavior. Biol Psychiatry. 2021;89:1058-1072.
• Xiao MF, Xu D, Craig MT, Pelkey KA, Chien CC, Shi Y, Zhang J, Resnick S, Pletnikova O, Salmon D, Brewer J, Edland S, Wegiel J, Tycko B, Savonenko A, Reeves RH, Troncoso JC, McBain CJ, Galasko D, Worley PF. NPTX2 and cognitive dysfunction in Alzheimer’s Disease. Elife 2017; 6: e23798.
• Na Y, Park S, Lee C, Kim D, Park J, Sockanathan S, Huganir R, Worley PF. Real-time imaging reveals properties of glutamate-induced Arc/Arg 3.1 translation in neuronal dendrites. Neuron 2016; 91: 561-573.

Appointments

Primary Appointment in Neuroscience