Cornelius Gati
@gati.bsky.social
Incoming faculty at the Penn School of Medicine. Structural biology and pharmacology, with a focus on GPCRs and membrane transporters. 💊 🧪
https://www.gati-lab.com
https://scholar.google.com/citations?user=5t80YUAAAAAJ&hl=en
https://www.gati-lab.com
https://scholar.google.com/citations?user=5t80YUAAAAAJ&hl=en
Remember, remember the 5th of November. Today marks the tenth anniversary of my PhD defense. I'm officially old now. (fin)
November 5, 2025 at 4:23 PM
Remember, remember the 5th of November. Today marks the tenth anniversary of my PhD defense. I'm officially old now. (fin)
Huge thanks to our amazing team — and especially to my first graduate student Saif Khan (second from right), who spearheaded this project with incredible drive and creativity. Credit also goes to him for the stunning movie in the first post. (8/n)
November 5, 2025 at 4:23 PM
Huge thanks to our amazing team — and especially to my first graduate student Saif Khan (second from right), who spearheaded this project with incredible drive and creativity. Credit also goes to him for the stunning movie in the first post. (8/n)
Supported by extensive molecular dynamics simulations, we assembled the first half of the G protein activation pathway — a major step toward understanding how GPCRs translate drug binding into cellular signaling. (7/n)
November 5, 2025 at 4:23 PM
Supported by extensive molecular dynamics simulations, we assembled the first half of the G protein activation pathway — a major step toward understanding how GPCRs translate drug binding into cellular signaling. (7/n)
The mind-blowing part: a “latent” state — where the receptor and G protein both appear inactive, yet remain bound to each other. Naloxone traps this state, stalling activation. This likely explains its ability to block opioid signaling so effectively. (6/n)
November 5, 2025 at 4:23 PM
The mind-blowing part: a “latent” state — where the receptor and G protein both appear inactive, yet remain bound to each other. Naloxone traps this state, stalling activation. This likely explains its ability to block opioid signaling so effectively. (6/n)
To explore this further, we determined a series of four novel GDP-bound MOR–G protein structures — the first of their kind for any GPCR. Remarkably, the distribution of these states correlated with the efficacy of the respective ligand. (5/n)
November 5, 2025 at 4:23 PM
To explore this further, we determined a series of four novel GDP-bound MOR–G protein structures — the first of their kind for any GPCR. Remarkably, the distribution of these states correlated with the efficacy of the respective ligand. (5/n)
We developed a simple BRET-based assay — “nuc-BRET” — to approximate the nucleotide affinity (EC₅₀) of MOR–G protein complexes. We found a clear inverse correlation: Antagonists stabilize GDP binding, while agonists promote its release for GTP exchange. (4/n)
November 5, 2025 at 4:23 PM
We developed a simple BRET-based assay — “nuc-BRET” — to approximate the nucleotide affinity (EC₅₀) of MOR–G protein complexes. We found a clear inverse correlation: Antagonists stabilize GDP binding, while agonists promote its release for GTP exchange. (4/n)
Recent smFRET and DEER studies from the Kobilka lab (Zhang et al. 2024 Nature; Deutsch et al. 2025 bioRxiv, etc.) revealed clear links between MOR conformations and ligand efficacy. These findings inspired our next step. (3/n)
November 5, 2025 at 4:23 PM
Recent smFRET and DEER studies from the Kobilka lab (Zhang et al. 2024 Nature; Deutsch et al. 2025 bioRxiv, etc.) revealed clear links between MOR conformations and ligand efficacy. These findings inspired our next step. (3/n)
A big research theme in our lab: how do different drugs acting on the same receptor cause different levels of activity? This concept — called efficacy — lies at the heart of receptor pharmacology and drug discovery efforts. (2/n)
November 5, 2025 at 4:23 PM
A big research theme in our lab: how do different drugs acting on the same receptor cause different levels of activity? This concept — called efficacy — lies at the heart of receptor pharmacology and drug discovery efforts. (2/n)
μ-opioid receptors (MOR) mainly signal by activating G proteins. This happens when the G protein swaps its bound GDP molecule for GTP — triggering subunit dissociation and downstream signaling. A classic textbook cartoon, from Alberts et al. - Molecular Biology of the Cell: (1/n)
November 5, 2025 at 4:23 PM
μ-opioid receptors (MOR) mainly signal by activating G proteins. This happens when the G protein swaps its bound GDP molecule for GTP — triggering subunit dissociation and downstream signaling. A classic textbook cartoon, from Alberts et al. - Molecular Biology of the Cell: (1/n)
Excited to share our latest @nature.com: How does naloxone (Narcan) stop an opioid overdose? We determined the first GDP-bound μ-opioid receptor–G protein structures and found naloxone traps a novel "latent” state, preventing GDP release and G protein activation.💊🧪 🧵👇 www.nature.com/articles/s41...
November 5, 2025 at 4:23 PM
Excited to share our latest @nature.com: How does naloxone (Narcan) stop an opioid overdose? We determined the first GDP-bound μ-opioid receptor–G protein structures and found naloxone traps a novel "latent” state, preventing GDP release and G protein activation.💊🧪 🧵👇 www.nature.com/articles/s41...
Thrilled to share that I’ll be joining the Perelman School of Medicine at the University of Pennsylvania! Our lab will be relocating to the Department of Pharmacology in Jan ’26. We’re hiring at all levels—reach out if you’re interested! @isbupenn.bsky.social @pennmedicine.bsky.social
September 28, 2025 at 9:32 PM
Thrilled to share that I’ll be joining the Perelman School of Medicine at the University of Pennsylvania! Our lab will be relocating to the Department of Pharmacology in Jan ’26. We’re hiring at all levels—reach out if you’re interested! @isbupenn.bsky.social @pennmedicine.bsky.social
Excited to present our newest preprint on the structure-function relationship of anaphylatoxin complement receptors. A casual number of 19 structures deciphering ligand recognition mechanisms, G protein/arrestin and species specific signaling. Please check it out! 🧪💊 www.biorxiv.org/content/bior...
May 31, 2025 at 3:09 AM
Excited to present our newest preprint on the structure-function relationship of anaphylatoxin complement receptors. A casual number of 19 structures deciphering ligand recognition mechanisms, G protein/arrestin and species specific signaling. Please check it out! 🧪💊 www.biorxiv.org/content/bior...
Special thanks to Saif Khan, Zenia Motiwala, Zixin Zhang, Gye Won Han, and the rest of the group for making this happen. I also would like to thank our collaborators in the (Sush) Majumdar lab and Shenvi lab @shenvi.bsky.social for their support.
January 7, 2025 at 4:09 PM
Special thanks to Saif Khan, Zenia Motiwala, Zixin Zhang, Gye Won Han, and the rest of the group for making this happen. I also would like to thank our collaborators in the (Sush) Majumdar lab and Shenvi lab @shenvi.bsky.social for their support.
I am eternally grateful to the entire team, who put in an enormous amount of effort, for this manuscript to see the light of day. First and foremost our very own graduate student Aaliyah Tyson, who has been spearheading this work. Here, she is posing with the plates that went into the paper:
January 7, 2025 at 4:09 PM
I am eternally grateful to the entire team, who put in an enormous amount of effort, for this manuscript to see the light of day. First and foremost our very own graduate student Aaliyah Tyson, who has been spearheading this work. Here, she is posing with the plates that went into the paper:
microswitch motifs immediately adjacent to the orthosteric binding pocket resemble canonical 'inactive' conformations, while the receptor is still engaged with its cognate G protein.
January 7, 2025 at 4:09 PM
microswitch motifs immediately adjacent to the orthosteric binding pocket resemble canonical 'inactive' conformations, while the receptor is still engaged with its cognate G protein.
We took this to an extreme, and were able to reconstitute these complexes (wildtype KOR and G protein!) in vitro and were able to obtain cryoEM reconstructions up to 3 A resolution. Strikingly, we observed the receptor in an entirely unexpected conformation:
January 7, 2025 at 4:09 PM
We took this to an extreme, and were able to reconstitute these complexes (wildtype KOR and G protein!) in vitro and were able to obtain cryoEM reconstructions up to 3 A resolution. Strikingly, we observed the receptor in an entirely unexpected conformation:
Classically, GPCR antagonism assumes that receptors are blocked from interacting with G proteins. In the 90s Kenakin et al. have proposed the 'cubic ternary complex model', which suggests that GPCR:G protein complexes can either be 'active' or 'inactive'. pubmed.ncbi.nlm.nih.gov/8949584/
January 7, 2025 at 4:09 PM
Classically, GPCR antagonism assumes that receptors are blocked from interacting with G proteins. In the 90s Kenakin et al. have proposed the 'cubic ternary complex model', which suggests that GPCR:G protein complexes can either be 'active' or 'inactive'. pubmed.ncbi.nlm.nih.gov/8949584/
Excited to present our lab's new work on GPCR antagonism: Contrary to popular belief, we propose that inverse agonists can bind to and act via GPCR:G protein complexes. We show this at KOR, through cellular assays, radioligand binding and cryoEM studies. A thread. 💊 🧪 www.nature.com/articles/s41...
January 7, 2025 at 4:09 PM
Excited to present our lab's new work on GPCR antagonism: Contrary to popular belief, we propose that inverse agonists can bind to and act via GPCR:G protein complexes. We show this at KOR, through cellular assays, radioligand binding and cryoEM studies. A thread. 💊 🧪 www.nature.com/articles/s41...
An opioid with a literal, light-sensitive 'on/off switch' to avoid fatal side effects? Look no further - Azomorphine-3 (AM3)! The most exciting study I've been part of, thus far. With the labs of Seva Katritch, Dirk Trauner @dirktrauner.bsky.social and Josh Levitz.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
December 20, 2024 at 11:35 PM
An opioid with a literal, light-sensitive 'on/off switch' to avoid fatal side effects? Look no further - Azomorphine-3 (AM3)! The most exciting study I've been part of, thus far. With the labs of Seva Katritch, Dirk Trauner @dirktrauner.bsky.social and Josh Levitz.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Sharing highly encouraged: My lab has an opening for a postdoc, to study structural biology, biophysics and pharmacology of GPCRs in neuro- and immunobiology. Come join our diverse and collaborative team in sunny SoCal - please reach out with any questions! dornsife.usc.edu/gati/
December 7, 2024 at 4:57 AM
Sharing highly encouraged: My lab has an opening for a postdoc, to study structural biology, biophysics and pharmacology of GPCRs in neuro- and immunobiology. Come join our diverse and collaborative team in sunny SoCal - please reach out with any questions! dornsife.usc.edu/gati/
Hello everyone!
My name is Cornelius Gati and I'm an Assistant Professor at the University of Southern California.
Our lab studies GPCR signaling and pharmacology, with a focus on structural biology (#CryoEM) and biophysics techniques.
I’m excited to get connected with old and new friends!
My name is Cornelius Gati and I'm an Assistant Professor at the University of Southern California.
Our lab studies GPCR signaling and pharmacology, with a focus on structural biology (#CryoEM) and biophysics techniques.
I’m excited to get connected with old and new friends!
November 18, 2024 at 6:14 AM
Hello everyone!
My name is Cornelius Gati and I'm an Assistant Professor at the University of Southern California.
Our lab studies GPCR signaling and pharmacology, with a focus on structural biology (#CryoEM) and biophysics techniques.
I’m excited to get connected with old and new friends!
My name is Cornelius Gati and I'm an Assistant Professor at the University of Southern California.
Our lab studies GPCR signaling and pharmacology, with a focus on structural biology (#CryoEM) and biophysics techniques.
I’m excited to get connected with old and new friends!