Evan S. O'Brien, PhD

Assistant Professor of Biophysics and Biophysical Chemistry

https://www.linkedin.com/in/evan-o-brien-38230aba/

• New compound could supercharge naloxone in fight against opioid overdoses, Stanford Medine ( July 3, 2024)

• Drug can amplify naloxone’s effect and reduce opioid withdrawals, study shows, LOS Angeles Crimes (July 3, 2024)

• Negative allosteric modulation of the glucagon receptor by RAMP2, Cell 

• Membrane Proteins Have Distinct Fast Internal Motion and Residual Conformational Entropy, Wiley(10 April 2020)

• Defining the Apoptotic TriggerInteraction of Cytochrome c and Cardiolipin, Science Direct (25 December 2015)

G-protein coupled receptors, GPCR, cryoEM, nuclear magnetic resonance, structural biology, drug discovery

O’Brien Lab

My lab focuses on understanding and exploiting the complex signaling properties of human membrane proteins with a particular focus on G-protein coupled receptors (GPCRs). GPCRs adopt a very broad set of distinct conformations, the populations and dynamics of which are highly important for determining their diverse signaling outcomes. It is because of their complex signaling profiles as well as their involvement in nearly all areas of human physiology that GPCRs are the targets for >1/3 of all FDA approved drugs. We use cryo-electron microscopy in conjunction with various protein dynamics techniques (principally solution nuclear magnetic resonance (NMR)) to understand at the atomic level how receptor thermodynamics drives activity. To facilitate these studies, we are developing cryoEM and NMR methods suited for detailed characterizations of fleeting yet highly important GPCR intermediate states. In order to exploit our novel mechanistic insights into GPCR signaling, the lab develops new DNA-encoded library (DEL) screening approaches for use in small molecule discovery programs in conjunction with leading academic and industry collaborators. In short, we do GPCR biophysics with an eye towards the clinic!

https://scholar.google.com/citations?user=9SuLolkAAAAJ&hl=en

https://www.ncbi.nlm.nih.gov/myncbi/1Jw-ZKu8-5JQ5N/bibliography/public/

https://www.researchgate.net/profile/Evan-Obrien-2

• O’Brien, E.S., Rangari, V.A., El Daibani, A. et al. A µ-opioid receptor modulator that works cooperatively with naloxone. Nature 631, 686–693 (2024). https://doi.org/10.1038/s41586-024-07587-7

• O’Brien ES, Krishna Kumar K, Kobilka BK, “Allosteric modulators of the µ-opioid receptor and      cannabinoid receptor 1”. Patent Pending, US No. 63/426,812.
• O’Brien ES, Krishna Kumar K, Kobilka BK, Rangari V, Majumdar S, “Novel small molecule negative allosteric modulators of the mu-opioid receptor”. Patent Pending, US No. 63/649,033.

American Heart Association Postdoctoral Fellowship

CHEM-H Innovative Medicines Accelerator Award

SPARK Scholars Program

Program in Molecular Biophysics (PMB)

Biochemistry, Cellular and Molecular Biology (BCMB)

Cross Disciplinary Graduate Program in Biomedical Sciences (XDBio)

Biophysical Society

American Heart Association

International Narcotics Research Conference