@neal-lab
Associate Professor @UCSD| HHMI Freeman Hrabowski Scholar| Research on rhomboid proteins| Proud mom| Proud PI of a very demure & mindful lab|co-founder of BUMMP |1st Gen & Black in STEM|Associate Director Biological Sciences PhD Program
Congrats to first-author and amazing postdoc from my lab @nicola-scott.bsky.social and special thanks to @phdgprotein86.bsky.social lab, @drohsopretty.bsky.social lab, Dr. Dhanendra Tomar lab, and Dr. Mark Phillips lab!
Importantly, ORMDL3 is genetically linked to several major diseases, including asthma, inflammatory bowel disease, metabolic disorders, and cancer, highlighting the broader biomedical relevance of this work. This work wouldn't have been possible w/o massive tour de force effort across multiple labs!
Conceptually, this work expands ERAD beyond misfolded protein clearance.
Instead, Derlin-mediated ERAD can act as a spatial and quantity control system that regulates functional ER proteins to preserve organelle communication.
Why does this matter?
ORMDL3 is genetically linked to multiple diseases, including:
asthma, inflammatory bowel disease, metabolic disease, and cancer.
Our findings suggest ERAD safeguards cellular health by preventing pathological ORMDL3 accumulation.
Mechanistically, we identify ORMDL3, a regulator of sphingolipid metabolism, as a Derlin-dependent ERAD substrate.
Without Derlins → ORMDL3 accumulates and mislocalizes to ER–mitochondria contact sites, driving mitochondrial dysfunction.
We reveal Derlin-2 is dominant paralog for ER stress relief & loss of Derlin-2 and Derlin-3 disrupts mitochondrial homeostasis, including:
• altered ER–mitochondria contact sites
• impaired respiration
• defective Ca²⁺ handling
Linking ER protein quality control directly to mitochondrial function.
Although Derlins are core components of ERAD, their paralog-specific roles have remained unclear.
By analyzing all three in the same cellular context, we uncover clear non-redundant functions at the cellular level.
Another preprint is out from the Neal Lab! 🎉
Excited to share the first systematic side-by-side comparison of ERAD Derlin paralogs, revealing distinct cellular functions for Derlin-1, Derlin-2, and Derlin-3.
www.biorxiv.org/content/10.6...
Thank you VJ!💕
Massive congrats to first author Saroj Gourkanti and the entire team & collaborators!
So proud of this work... from CRISPR fish to live imaging to proteomics to mechanism.
New model:
Rhbdl2 functions as an immune checkpoint for regeneration, restraining Rac2-dependent macrophage accumulation
and preventing excessive tissue growth.
Then proteomics dropped the bomb 💣
⬆ Rac2 protein levels in rhbdl2 mutants
No major mRNA changes.
This is post-transcriptional control.
Intramembrane proteolysis regulating a small GTPase axis.
rhbdl2⁻/⁻ fish regenerate MORE.
Same development.
Same morphology.
But after injury → accelerated fin regrowth.
We uncovered an immune brake on regeneration.
The twist?
It’s not developmental.
It’s immune.
rhbdl2⁻/⁻ larvae show:
⬆ macrophage accumulation at wounds
We deleted a rhomboid protease… and regeneration went into overdrive.
New preprint from the Neal Lab!
Rhbdl2 restrains macrophage-driven regeneration in zebrafish. 🐟🔥 #Regeneration #InnateImmunity
www.biorxiv.org/content/10.6...
“[We] found that [rhbdl2] does not affect normal development, but triggers enhanced regenerative growth following injury, accompanied by increased macrophage accumulation at the wound site, which is accompanied by increased early apoptosis and proliferation.”
New work from @neal-lab.bsky.social 🐟
Congrats on all fronts🎊🎉🎉🎉🎉so well deserved!
I am SO incredibly excited to announce the launch of a global list of Inspiring Black Scientists. You can use this list to nominate and connect with researchers. Please share and join us in highlighting these outstanding scientists for #BlackHistoryMonth and beyond!
www.wiley.com/en-us/resear...
Happy Holidays from @neal-lab.bsky.social and @bummpatucsd.bsky.social friends!
What an incredible moment celebrating UC LEADS’ 25th anniversary! This program opened doors for me and so many others pursuing academic careers. Hearing alumni share how transformative it has been is living proof that access, mentorship, and opportunity work. This is impact.
The #ABRCMS2025 conference was my first scientific meeting as an undergrad, and it was the experience that propelled me into science. Being back this week, surrounded by brilliant, aspiring young scientists, has been incredible. #seeingisbelieving
Does anyone have examples of F32 supporting documents in the new format (starting August of this year) they'd be willing to share? We're specifically looking for goals, preparedness, training activities and timeline for an F32 resubmission for the December deadline. Any help very much appreciated! 🙏
Amazing turn out for @bummpatucsd.bsky.social Welcome Lunch♥️♥️♥️
Another Neal lab retreat in the books. We mapped our yearly goals, came up with collaborative big picture ideas for future projects and most importantly, strengthened our team bond 💪🏽we are all in this together💪🏽
During these uncertain times, I’m very happy to see that my institution, @scripps.edu has an open tenure-track Assistant Professor position. Any field in Chemistry or Biology is welcome. I’d especially love to see fellow neuroscientists apply. Please repost!
apply.interfolio.com/174756
and makes the case for why vertebrate models are urgently needed in this field.
Proud of this collaborative effort from the lab.
Huge congratulations to first author Saroj Gourkanti and our amazing co-authors of the Neal lab — Yazmin, Jackie, Rosa, @dagarwal.bsky.social, and Kristina. This work highlights the emerging roles of rhomboid proteases and pseudoproteases,from development to disease .
Thrilled to share that our review, “Holding Out for a Model: Rhomboid Superfamily in Vertebrate Development and Disease,” is now published in Journal of Cellular Physiology!
onlinelibrary.wiley.com/doi/10.1002/...
LOVE TO SEE THIS! So well deserved and congratulations 🎉🎉🎉🎉🎉
💪🏽💪🏽💪🏽
Can’t wait to read this! Congrats to all🎉♥️