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Paul F. Worley, M.D.

Photo of Dr. Paul F. Worley, M.D.

Professor of Neuroscience

Research Interests: Immediate early genes (IEGs); Addiction; Molecular basis of long-term learning and memory; Molecular mechanisms of neuronal plasticity ...read more

Background

Dr. Paul F. Worley is a professor of neuroscience at the Johns Hopkins University School of Medicine. An expert in the molecular basis of specific forms of long-term learning and memory, Dr. Worley serves on the faculty of the Institute for Basic Biomedical Sciences and as an associated investigator with the Alzheimer’s Disease Research Center.

Dr. Worley’s laboratory focuses on a class of proteins found at the interfaces of connecting neurons (synapses) that ramp up as the neurons engage in information processing and storage. These proteins directly modify the strength of the signals sent between neurons and are essential for information storage.

Recent work reveals how molecules that regulate reward-signaling neuronal responses (such as dopamine) can selectively strengthen communication across synapses – and implicates this process in addiction.

Dr. Worley’s research also has clinical potential in the treatment of patients with degenerative memory conditions such as Alzheimer’s disease.

...read more

Titles

  • Professor of Neuroscience
  • Professor of Neurology

Departments / Divisions

Research & Publications

Research Summary

Dr. Worley’s laboratory examines the molecular basis of learning and memory.

In particular, research in the Worley Lab have cloned a set of immediate early genes (IEGs) that are rapidly transcribed in neurons involved in information processing, and that are essential for long-term memory.

IEG proteins can directly modify synapses and provide insight into cellular mechanisms that support synapse-specific plasticity.

For example, Narp is secreted and induces excitatory synapse formation. Homer catalyzes conformational coupling of multi-protein machines involved in calcium signaling. Rheb regulates mTor (target of rapamycin) and protein translation. Arc induces the formation of endosomes that function in trafficking of glutamate receptors.

Thus, rapid de novo transcription provides novel insights into the cellular and neural network basis of behavioral plasticity.

Lab Website: Paul Worley Lab
Core Facility: ES Cell Targeting Core Facility

Selected Publications

Wu J, Petralia RS, Kurushima H, Patel H, Jung MY, Volk L, Chowdhury S, Shepherd JD, Dehoff M, Li Y, Kuhl D, Huganir RL, Price DL, Scannevin R, Troncoso JC, Wong PC, Worley PF. "Arc/Arg3.1 regulates an endosomal pathway essential for activity-dependent β-amyloid generation." Cell. 2011 Oct 28;147(3):615-28.

Hu JH, Yang L, Kammermeier P, Moore CG, Brakeman PR, Tu JC, Yu S, Petralia RS, Li Z, Zhang PW, Park JM, Dong X, Xiao B and Worley PF. "Preso1 dynamically regulates Group1 metabotropic glutamate receptors." Nature Neuroscience. 2012.

Okuno H, Akashi K, Ishii Y, Yagishita-Kyo N, Suzuki K, Nonaka M, Kawashima T, Fujii H, Takemoto-Kimura S, Abe M, Natsume R, Chowdhury S, Sakimura K, Worley PF, Bito H. "Inverse Synaptic Tagging of Inactive Synapses via Dynamic Interaction of Arc/Arg3.1 with CaMKIIβ." Cell. 2012 May 11; 149(4):886-98.

Bangash MA, Park JM, Melnikova T, Wang D, Jeon SK, Lee D, Syeda S, Kim J, Kouser M, Schwartz J, Cui Y, Zhao X, Speed HE, Kee SE, Tu JC, Hu JH, Petralia RS, Linden DJ, Powell CM, Savonenko A, Xiao B, Worley PF. Enhanced Polyubiquitination of Shank3 and NMDA receptor in a Mouse Model of Autism. Cell. 2011 May 27;145(5):758-772.

Chang MC, Park JM, Pelkey KA, Grabenstatter HL, Xu D et al. Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons. Nat Neurosci. 2010; 13(9):1090-7.

Academic Affiliations & Courses

Graduate Program Affiliation

Neuroscience Graduate Program

Biochemistry, Cellular and Molecular Biology Graduate Program

Cellular and Molecular Medicine

Visual Neuroscience

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