DiPaolo Lab

@bryan_johnson We have expertise in AIG and engineering immune regulation/tolerance and are following this journey!

My plan to cure autoimmune gastritis To our knowledge, no one has ever done this to try and cure an autoimmune disease. Context: In May, I got diagnosed with autoimmune gastritis (AIG). We found it by taking a tissue biopsy of my stomach. My immune cells are confused, causing my stomach to eat itself. AIG stops your body from absorbing nutrients like iron and B12, and can eventually lead to cancer. It likely started decades ago when I was diagnosed with hypothyroidism when 21 years old. The thyroid and stomach are closely linked in your immune system. I feel fortunate that I've been taking such good care of my body for the past five years as my condition would otherwise be much more severe. Millions of people are affected by this disease and are undiagnosed. Standard of care tells you that you can’t do anything about it. That’s old fashioned. Here is how we are going to try and cure it: Step 0: find and diagnose the disease ✅ AIG is rarely caught early because symptoms are subtle. Early warnings are low iron and B12, but when hemoglobin and hematocrit look normal, doctors routinely miss it because there are no obvious signs of anemia. A standard colonoscopy won't find it either, because it only checks the lower digestive tract, not the stomach. It was only through a highly targeted stomach biopsy that we found it. Even biopsies can miss it if they don't sample the exact right spots. Most people with AIG go undiagnosed. Step 1: Map my immune system ✅ Last Thursday, I had a blood draw to isolate and decode 1 million of my immune cells. Think of your immune cells as trillions of soldiers. Each carries a unique key designed to unlock and destroy a specific threat, like a virus or bacteria. A standard blood test allows you to see how many soldiers you have, but not their keys. Sequencing one million individual immune cells allows us to read the exact pattern of the teeth on every single key. This is important for my autoimmune gastritis (AIG) because a specific platoon of rogue soldiers has developed keys that unlock an attack on my stomach lining. Right now, we don’t know who they are. This test will inform us of which soldiers have gone rogue and are attacking me from within. Once we know the soldier and key, we know what therapy path to pursue to shut them down. Step 2: Catch the rogue soldiers I will be getting a second biopsy from my stomach because we need to collect live tissue. We are currently planning out the logistics of getting the sample from my stomach to the lab. We need these live cells because the initial blood tests showed the antibodies, which prove that an attack is happening, but doesn’t show us the actual rogue soldier doing the damage which is a T-cell. The live sample will allow us to match the immune system mapping we did to the live T-cells. Step 3: Build an early warning system To keep an eye on the disease as we work towards a therapy, we’re building an early warning system. I'll have my blood drawn every two weeks and we’ll pair that information with wearable data to look for flare ups. This is important because the attack happens without producing symptoms that I can easily feel. Step 4: Create a “Bryan in a dish” testing model, a miniature of my immune system At the same time, we are taking a massive sample of my immune cells and deep freezing them (cryopreservation) for two reasons: a) we’ll create a living lab: using these cells to replicate my immune environment in a lab dish. This allows us to test experimental drugs and therapies on my actual live cells before putting them into my body. b) it creates a back up plan for me by preserving the raw cellular material needed for targeted rejuvenation therapies in the future. Step 5: Build precision guided therapies to end the attack Once we know who the rogue soldiers are, we will engineer a therapy designed uniquely for them. The trick is only turning off the rogue soldiers while leaving all the other healthy ones functioning as they are. For safety checks, we’ll do two test runs: 1) we’ll run the therapy through a computer model that has my biology to evaluate how my molecules interact. 2) We will take my actual cells that we froze in Step 4 and watch them interact for real. If both are successful, we’ll pursue one of four therapies: a) fix the mistake my cells are making, restoring my immune system's natural off switches b) teach the rogue cells to tolerate my stomach instead of attacking it c) design smart molecules that physically plug into the rogue cells and turn them off d) build soldiers who will track down and eliminate the rogue soldiers causing the damage

@bryan_johnson Following to keep updated, my lab studies autoimmune gastritis extensively, it would be interesting to chat.

Massive blood draw today: > decoding 1 million immune cells > identifying the rogue clones attacking my stomach > causing the autoimmune gastritis This is incredible technology. Think of your immune cells as trillions of soldiers. Each carries a unique key designed to unlock and destroy a specific threat, like a virus or bacteria. A standard blood test allows you to see how many soldiers you have, but not their keys. Sequencing 1 million individual immune cells allows us to read the exact pattern of the teeth on every single key. This is important for my autoimmune gastritis (AIG) because a specific platoon of rogue soldiers has developed keys that unlock an attack on my stomach lining. Right now, we don’t know who they are. This test will inform us of which soldiers have gone rogue and are attacking me from within. Once we know soldier and key, we know what therapy path to pursue to shut them down. Other makers in this blood draw: Ferritin, Soluble Transferrin Receptor, Iron and TIBC, Transferrin Saturation, Erythropoietin (EPO), Reticulocyte Count, CBC With Differential/Platelet, Phosphorus, Comprehensive Metabolic Panel (14), Antiparietal Cell Antibody, Intrinsic Factor Abs, Gastrin, Chromogranin A, Celiac Ab tTG IgA w/Rflx, IL-2 Receptor Alpha, T- and B-Lymphocyte/Nat Killer, Complement C3, Complement C4, Tumor Necrosis Factor-Alpha, Interleukin-6, HLA DRB1/3/4/5/DQB1, Cardiometabolic Report, Total Glutathione, Selenium, Coenzyme Q10, Oxidized LDL, Essential Fatty Acid Profile, Lp-PLA2 Activity, Myeloperoxidase (MPO), Vitamin D 25-Hydroxy, Magnesium, Copper, Zinc, Vitamin B12, Methylmalonic Acid, Folate, Hemoglobin A1c, GlycA, Fructosamine, C-Reactive Protein Cardiac, NT-proBNP, Lipid Panel, Apolipoprotein A-1, Apolipoprotein B, NMR LipoProfile, Lipoprotein (a), p-tau217, S-100B Protein, Neurofilament Light Chain, Glial Fibrillary Acid Protein

Next week at @PEGSboston, Ahmet Vakkasoglu & Richard DiPaolo will present preclinical data on our TGF-β/IL-2 fusion protein CUE-401, supporting its ability to expand existing T regs and induce new Tregs in #autoimmune & #inflammatory diseases. Join us: pegsummit.com

Big week for the DiPaolo Lab, Nick, now Dr. Nicholas Jackson defended his thesis, @challen_p gave an outstanding talk at @DDWMeeting and Lily McMorrow @SLUMDPhD present a great poster! Proud mentor here.

@The_Choi_Lab Congratulations!

I’m happy to share that I’ve been appointed to a new role as VICC Gastrointestinal Cancer Research Program Fellow at VUMC!

Excited for Nicholas Jackson as he graduates soon as Dr. Nicholas Jackson (PhD)! Led standout IL‑2/TGF‑β immunology work with @CueBiopharma. Excellent scientist & communicator—now seeking post‑PhD opportunities. Preprint: biorxiv.org/content/10.648…

Take a look at this article from our group/collaborators @CueBiopharma describing an exciting new strategy to restore immune tolerance— CUE-401 co-delivers attenuated IL-2 and TGF-β3 to selectively activate Tregs and suppress autoimmunity biorxiv.org/content/10.648…

Registration is now open for Gastrointestinal Tract XXII Snowbird Ski Resort | Salt Lake City, UT August 30-September 3, 2026 #GITractSRC events.faseb.org/event/728860a1… @GoldenringLab @magnesslab @The_Choi_Lab @JosephBurclaff @millsjc67 @BusadaLab @DelgiornoKathy @AmyEngevik

This month, we’re spotlighting Dr. Rich DiPaolo, Prof. & Chair of Molecular Microbiology & Immunology at St. Louis University, and prominent immunologist, as he shares promising preclinical data on CUE-401, our lead #autoimmune candidate. Get to know Dr. DiPaolo #OnCUE.

@DelgiornoKathy I'll see you there, right Dr. DelGiorno?

10/10, highly recommend one of my favorite meetings

Registration is open for this great meeting! GI Tract XXII: “Molecular and Cellular Advances Towards Discovery and Treatment” conference, to be held in Snowbird/Salt Lake City, UT, August 30–September 4, 2026. Abstract Submission Deadline: June 7, 2026 events.faseb.org/event/728860a1…

The annual SLU MMI trip to Giordano’s for deep dish pizza! Great meeting, delicious pizza #AIC2025 @autumnimmuno @AlspachLab

Students went all out for Halloween!

It's time to make hotel reservations for #AIC2025! To take advantage of special conference pricing, bookings are due this Friday (Oct 24th)! autumnimmunologyconference.org/venue

Heads up! Applications for the #AIC2025 John Wallace Fellowship are now due Friday, 10/10. Check the website for eligibility and application details: autumnimmunologyconference.org/john-wallace-f…

Nice comment on a recent article article by @millsjc67 and Jeffrey W Brown, called cathartocytosis, where stomach (chief) cells “vomit” out their contents to quickly shrink and repair damaged tissue. the-scientist.com/stomach-cells-…

BREAKING NEWS The 2025 #NobelPrize in Physiology or Medicine has been awarded to Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi “for their discoveries concerning peripheral immune tolerance.”

BREAKING NEWS❗ NIH establishes nation's first dedicated organoid development center to reduce reliance on animal modeling. bit.ly/4pBYT9T

The 2017 @amergastroassn - @gastriccancerfd research scholar award was critical for Jose Saenz, MD, PhD to receiving a 5-year grant from the @NIHFunding to continue his H. pylori research and allow him to build upon the insights he gained. gastriccancer.org/2019/12/12/fou…

Interested in the opportunity for one-on-one interactions with leading scientists at #AIC2025? Register for the Meet the Speakers dinner! This event often sells out, so sign up ASAP! autumnimmunologyconference.org/meet-the-speak…