O’Neill Lab

In the O’Neill Lab, we focus on developing new imaging and optogenetic methods to interrogate GPCR signaling in healthy and diseased brains, over scales ranging from individual synapses to whole brain neuroanatomy. Our goal is to provide technologies that can be widely adopted by neuroscientists with diverse research interests. We also engage in collaborations in order to apply our tools to better understand drug addiction.

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Research

Optogenetic control of GPCR and G protein signaling

In order to understand GPCR signaling dynamics with subcellular detail, we have developed several tools for optogenetic control of GPCRs and G protein subunits. Our early work focused on using these tools to dissect the intracellular signaling networks that control polarization and directional migration of immune cells. We currently focus on leveraging optical control of GPCR signaling to generate new tools for studying neural circuit functions. For example, we recently collaborated with Bryan Copits (Washington University in St. Louis) and Michael Bruchas (University of Washington), to develop a bistable, photoswitchable GPCR for optically controlled inhibition of neurotransmission at axon terminals. We are currently collaborating with the Copits Lab and Hugo Tejeda (NIMH) to develop next generation GPCR-based optogenetic tools with synapse-subtype specificity.

Neuroanatomical imaging of GPCR signaling

We are developing a new approach for in situ imaging of G protein activation by GPCRs in brain tissue sections. The goal is to quantify, with subcellular resolution and neuroanatomical detail, GPCR activation of the different G protein subtypes. The long term goal is to use this approach to identify specific changes in GPCR signaling that occur in response to chronic drug use, chronic stress, or chronic pain, to help identify pharmacological targets for new therapies.

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Personnel

Patrick R. O’Neill, Ph.D.
Principal Investigator
Hatos Center for Neuropharmacology
Semel Institute
Department of Psychiatry and Biobehavioral Sciences

Current lab members

Anna Shiriaeva Postdoc	September 2024 – present
Coby Bowman Lab Assistant UCLA undergraduate, class of 2024	August 2024 – present March 2023 – present
Nadia Rehman UCLA undergraduate, class of 2025	November 2022 – present
Jackie Caplan UCLA undergraduate, class of 2025	November 2022 – present
Jane Shohdy UCLA undergraduate, class of 2025	October 2023 – present
Tracy Ngyuen UCLA undergraduate, class of 2026	January 2024 – present
Lily Anderson UCLA undergraduate, class of 2025	July 2024 – present
Tanvi Mahajani UCLA undergraduate, class of 2027	October 2024 – present
Louie Angelo Latosquin UCLA undergraduate, class of 2027	April 2025 – present
Haley Buttimer UCLA undergraduate, class of 2026	April 2025 – present
Rohan Gianchandani UCLA undergraduate, class of 2028	April 2025 – present

Former lab members

Noor Wani UCLA undergraduate, class of 2024	Fall 2022 – June 2024
Ella Whitehouse UCLA undergraduate, class of 2024 Next position: Neuroscience PhD Student, UCLA	Fall 2022 – June 2024
Harbaksh Kaur UCLA undergraduate, class of 2024	August 2024 – December 2024
Lauren Chao UCLA undergraduate, class of 2024 Next position: Life Science Research Professional at Stanford University	Fall 2023 – June 2024
Veda Ouwehand UCLA undergraduate, class of 2024 Next position: Neuroscience MSc Student, Vrije University Research Intern, Center for Neurogenomics & Cognitive Research	July 2023 – April 2024
Istabraq Dalieh Masters Student, Charles E. Drew University Next position: Laboratory Technician at Keck Medicine USC DDS Student at Boston University Goldman School of Dental Medicine	Jan 2022 – Aug 2022
Lisa Bass Research Assistant Student Volunteer Next position: Study Coordinator at New School Research Marriage, Child, and Family Counseling Graduate Student at CSU Sacramento	Dec 2020 – July 2021 Oct 2019 – Mar 2020

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Publications

Google Scholar:
https://scholar.google.com/citations?user=ogDreWAAAAAJ&hl=en&oi=ao

Pubmed:
http://www.ncbi.nlm.nih.gov/sites/myncbi/patrick.o’neill.1/bibliography/43837672/public/?sort=date&direction=descending

1. Alayoubi M, Rodrigues A, We C, Whitehouse E, Nguyen J, Cooper Z, O’Neill PR, Cahill CM. Elucidating interplay between myrcene and cannabinoid receptor 1 receptors to produce antinociception in mouse models of neuropathic pain. Pain, 2025.
   
2. Aguirre CG, Woo JH, Romero-Sosa JL, Rivera ZM, Tejada AN, Munier JJ, Perez J, Golfarb M, Das K, Gomez M, Ye T, Pannu J, Evans K, O’Neill PR, Spigelman I, Soltani A, Izquierdo Z. Dissociable contributions of basolateral amygdala and ventrolateral orbitofrontal cortex to flexible learning under uncertainty. Journal of Neuroscience, 2024.
   
3. Munier JJ, Shen S, Rahal D, Hanna A, Marty VN, O’Neill PR, Fanselow MS, Spigelman I. Chronic intermittent ethanol exposure disrupts stress-related tripartite communication to impact affect-related behavioral selection in male rats. Neurobiology of Stress, 2023.
   
4. O’Neill PR, Copits BA, Bruchas MR. Optical approaches for dissecting GPCR signaling. GPCRs as Therapeutic Targets, 2022
   
5. Copits BA, Gowrishankar R, O’Neill PR, Li JN, Girven KS, Yoo JJ, Meshik X, Parker KE, Spangler SM, Elerding AJ, Brown BJ, Shirley SE, Ma KKL, Vasquez AM, Stander MC, Kalyanaraman V, Vogt SK, Samineni VK, Patriarchi T, Tian L, Gautam N, Sunahara RK, Gereau IV RW, Bruchas MR. A photoswitchable GPCR-based opsin for presynaptic terminal inhibition. Neuron, 2021
   
6. Mann A, Mouledous L, Froment C, O’Neill PR, Dasgupta P, Guenter T, Brunori G, Kieffer BL, Toll L, Bruchas MR, Zaveri NT, Schulz S. Agonist-selective NOP receptor phosphorylation correlates in vitro and in vivo and reveals differential post-activation signaling by chemically diverse agonists. Science Signaling, 2019
   
7. Meshik X, O’Neill PR, Gautam N. Physical plasma membrane perturbation using subcellular optogenetics drives integrin-activated cell migration. ACS Synthetic Biology, 2019
   
8. O’Neill PR, Castillo-Badillo JA, Meshik X, Kalyanaraman V, Melgarejo K, Gautam N. Membrane flow drives an adhesion-independent amoeboid cell migration mode. Developmental Cell, 2018
   
9. O’Neill PR, Kalyanaraman V, Gautam N. Subcellular optogenetic activation of Cdc42 controls local and distal signaling to drive immune cell migration. Molecular Biology of the Cell, 2016
   
10. O’Neill PR and Gautam N. Subcellular optogenetic inhibition of G proteins generates signaling gradients and cell migration. Molecular Biology of the Cell, 2014. Selected as MBoC “Paper of the Year”
    
11. O’Neill PR, Karunarathne WKA, Kalyanaraman V, Silvius JR, Gautam N. (2012) G protein signaling leverages subunit-dependent membrane affinity to differentially control bg translocation to intracellular membranes. Proceedings of the National Academy of Sciences, 2012
    
12. O’Neill PR, Young K, Schiffels D, Fygenson DK. Few-atom fluorescent silver clusters assemble at programmed sites on DNA nanotubes. Nano Letters, 2012
    
13. Karunarathne WKA, O’Neill PR, Martinez-Espinosa PL, Kalyanaraman V, Gautam N. All G protein bg complexes are capable of translocation on receptor activation. Biochemical and Biophysical Research Communications, 2012
    
14. O’Neill PR, Gwinn EG, Fygenson DK. UV excitation of DNA stabilized Ag cluster fluorescence via the DNA bases. The Journal of Physical Chemistry C, 2011
    
15. Driehorst T, O’Neill P, Goodwin PM, Pennathur S, Fygenson DK. Distinct conformations of DNA-stabilized fluorescent silver nanoclusters revealed by electrophoretic mobility and diffusivity measurements. Langmuir, 2011
    
16. O’Neill PR, Velazquez LR, Dunn DG, Gwinn EG, Fygenson DK. Hairpins with Poly-C loops stabilize four types of fluorescent Ag_n:DNA. The Journal of Physical Chemistry C, 2009
    
17. Gwinn EG, O’Neill P, Guerrero AJ, Bouwmeester D, Fygenson DK. Sequence-dependent fluorescence of DNA-hosted silver nanoclusters. Advanced Materials, 2008
    
18. O’Neill P, Rothemund PWK, Kumar A, Fygenson DK. Sturdier DNA nanotubes via ligation. Nano Letters, 2005
    
19. Royer JR, O’Neill P, Becker N, Ahlers G. Wave-number selection by target patterns and sidewalls in Raleigh-Benard convection. Physical Review E, 2004

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Opportunities

The O’Neill Lab (https://www.semel.ucla.edu/oneill-lab) at UCLA is seeking a postdoctoral scholar to join our team in the Hatos Center for Neuropharmacology. We are affiliated with the Semel Institute for Neuroscience and Human Behavior and the Department of Psychiatry and Biobehavioral Sciences. 

Our research focuses on developing new imaging methods and optogenetics strategies for diverse neuroscience applications. We are especially interested in developing new methods for optogenetic control of G protein coupled receptor (GPCR) signaling and synaptic transmission, and new imaging methods for neuroanatomical measurements of GPCR signaling. The postdoctoral scholar will be involved in establishing these new technologies using a combination of protein engineering, cell culture (cell lines and primary neurons), high throughput assays for GPCR signaling, cryosectioning, and both fixed and live cell imaging. Additionally, there will be excellent opportunities for collaboration within the Hatos Center to apply these new methods in rodent models of chronic pain and drug addiction.

Candidates are expected to have a PhD in a relevant area: Neuroscience, Pharmacology, Biochemistry, etc. We especially encourage applications from candidates with experience in one or more of the following: GPCR signaling, protein engineering, live cell imaging, optogenetics.

Located in an urban setting, UCLA is California’s largest university with a diverse student body of 38,000 undergraduate and graduate students, approximately 25% that come from underrepresented minority groups. As a campus with a continually growing diverse student body, we encourage applications from women, minorities, and individuals with a commitment to the success of underrepresented groups in behavioral science.

Interested candidates should provide a cover letter and forward their CV and names of 3 references to:

Patrick O’Neill, PhD
Assistant Researcher
Hatos Center for Neuropharmacology
Department of Psychiatry and Biobehavioral Sciences
Semel Institute for Neuroscience and Human Behavior
UCLA, Los Angeles, CA
proneill@ucla.edu