David M. Sabatini

Studying rapamycin and mTOR and metabolism for a long time.

[IsomLab @danIsomLab]

Out online today in @Nature. The known protein universe holds hundreds of millions of members, yet most remain unexplored, a vast biological darkness that may hold important clues to human health and disease. We went looking in it.
https://t.co/EkE584rOQL

[Steven Pinker @sapinker]

One hundred percent of professors will agree with this: College campuses are being suffocated by administrators https://t.co/HlqeqKL0oG via @BostonGlobe

[Cell Stem Cell @CellStemCell]

Online Now! IGF2 acts downstream of Hippo signaling to regulate organ growth and restore liver regeneration in aging https://t.co/j6ad7u0Shu #stemcells

[Gilad Evrony @giladevrony]

Very excited to share our new paper, published in Cell!

We found that caloric restriction (CR) in mice reduces somatic mutation burdens across the genome, and that this effect has some surprising features.

🧵👇
1/8

[Rutter Lab @RutterLab]

Congratulations to our tremendous graduating fellow, @N8Krah, on his newest preprint! Nate will be starting his lab here at @UofUHematology @huntsmancancer. We're excited to continue supporting his research!

[David M. Sabatini @DMSabatini]

Very nice paper
https://t.co/iJBoX3hUwa

[Jorge I. Castillo-Quan, MD, PhD @CastilloQuan_JI]

I am recruiting 2 Ph.D. students to join the Cellular & Organismal Resilience and Aging (CORA) Laboratory at Ohio University @OhioBioSciences @OHIOartsandsci in Fall 2027.

Details: https://t.co/PTrvE6U2LT

#science #research #aging #metabolism #proteostasis #geroscience #phd

[Y. Ryan Lu @Y_Ryan_Lu]

Humbled and grateful to be named one of @techreview Innovators Under 35, and honored to be featured by @antonioregalado. Thank you to the judges and committee for this recognition. It may help carry me through those inevitable moments of self-doubt when confronting the complexity of biology.

I’ve been incredibly fortunate to have mentors: @davidasinclair, @JswLab, @bruce_ksander, Zhigang He, Tian Xu, Yang Shi, and the late Michael Bonkowski—who gave me the freedom and support to pursue bold ideas and guided me along the way, as well as family, colleagues, and students who made this journey possible.

Grateful to see the OSK discovery, one success after four years of failures, come this far through the continued efforts of @davidasinclair and the team at @LifeBiosciences, and hopeful that the ongoing clinical trial will ultimately help patients. Uncovering GSTA4 as an OSK effector took another five years—and translating it into something that might help patients will take many more.

Science takes time, but it’s worth the wait. As Frank Lloyd Wright said, “My favorite project is always the next one.” Stay tuned! 👁️🧬🔬

https://t.co/eaXdbY09Sr

[David M. Sabatini @DMSabatini]

A friend pointed out this new RPMI cell culture media from Sigma that lacks leucine, arginine, and lysine (-LRK). This is exactly the media we would make in house to study amino acid sensing by mTORC1 so should be useful to many:

https://t.co/0OadrTG9h7

[David M. Sabatini @DMSabatini]

Few scientists know mitochondria better than Jared. Worth listening to.

[Andrew D. Huberman, Ph.D. @hubermanlab]

The new Huberman Lab episode is out: How Mitochondria Control Your Metabolism | Dr. Jared Rutter (@rutterlab)

0:00 Jared Rutter
2:29 Metabolism, Cells; Aging
8:36 Mitochondria, Origin & Cell Complexity
13:07 Sponsors: Joovv & BetterHelp
15:16 Mitochondria Genome, Inheritance
18:18 Mitochondria & Spatial Distribution; Cell-Specific Metabolism
25:59 Nutrient Energy, Hormones, Fat Cells
31:13 Glucose, ATP Conversion, Pyruvate
36:41 Cell Choice: Energy or Growth, Cancer; Virus
46:02 Sponsors: AG1 & Eight Sleep
48:36 Microbiome, Role of Humans
51:44 Molecule Discovery Process, MPC1, MPC2
59:42 Cell Resource Sensing, Fasting, Glucagon, Fat Cells; Neurons, Heart
1:07:03 Cell Resource Allocation, MPC, Heart Failure; Disease
1:11:46 Sponsor: Function
1:13:24 Cell Size vs Fuel Balance, Cell Identity & Disease
1:20:43 MPC Discovery, Genetics, Model Systems
1:24:29 Lactate, Oxygen, Exercise; Energy Prioritization Hierarchy
1:31:32 Cancer, Mutations, Metabolism Changes & Warburg Effect
1:36:18 Cancer Challenges & Therapies
1:43:00 Therapy Combinations, Unique Cancer Mutations & Metabolism
1:48:31 Technology to Visualize Metabolism; Disease, Metabolism & Scents
1:56:34 Excess Energy & Mitochondria, Reactive Oxygen Species
2:01:12 Zero-Cost Support, YouTube, Spotify & Apple Follow, Reviews & Feedback, Sponsors, Protocols Book, Social Media, Neural Network Newsletter

Includes paid partnerships.

[Andrew D. Huberman, Ph.D. @hubermanlab]

The new Huberman Lab episode is out: How Mitochondria Control Your Metabolism | Dr. Jared Rutter (@rutterlab)

0:00 Jared Rutter
2:29 Metabolism, Cells; Aging
8:36 Mitochondria, Origin & Cell Complexity
13:07 Sponsors: Joovv & BetterHelp
15:16 Mitochondria Genome, Inheritance
18:18 Mitochondria & Spatial Distribution; Cell-Specific Metabolism
25:59 Nutrient Energy, Hormones, Fat Cells
31:13 Glucose, ATP Conversion, Pyruvate
36:41 Cell Choice: Energy or Growth, Cancer; Virus
46:02 Sponsors: AG1 & Eight Sleep
48:36 Microbiome, Role of Humans
51:44 Molecule Discovery Process, MPC1, MPC2
59:42 Cell Resource Sensing, Fasting, Glucagon, Fat Cells; Neurons, Heart
1:07:03 Cell Resource Allocation, MPC, Heart Failure; Disease
1:11:46 Sponsor: Function
1:13:24 Cell Size vs Fuel Balance, Cell Identity & Disease
1:20:43 MPC Discovery, Genetics, Model Systems
1:24:29 Lactate, Oxygen, Exercise; Energy Prioritization Hierarchy
1:31:32 Cancer, Mutations, Metabolism Changes & Warburg Effect
1:36:18 Cancer Challenges & Therapies
1:43:00 Therapy Combinations, Unique Cancer Mutations & Metabolism
1:48:31 Technology to Visualize Metabolism; Disease, Metabolism & Scents
1:56:34 Excess Energy & Mitochondria, Reactive Oxygen Species
2:01:12 Zero-Cost Support, YouTube, Spotify & Apple Follow, Reviews & Feedback, Sponsors, Protocols Book, Social Media, Neural Network Newsletter

Includes paid partnerships.

[Cell @CellCellPress]

In the latest issue! Co-option of lysosomal machinery shapes the evolution of the intracellular photosymbiosis supporting coral reefs https://t.co/K3kx83BiDG

[PNASNews @PNASNews]

Meet Dr. Hidde Ploegh of Boston Children’s Hospital, a @PNASNexus Associate Editor and distinguished NAS member who brings expertise in cellular and molecular medicine to the journal’s editorial board.

Explore the full Editorial Board: https://t.co/HEZTAQKxRG

[IOCB Prague @IOCBPrague]

🔬 At IOCB, we have local access to a basic #cryoEM screening microscope and dedicated instrumentation for 3D ED in the @tm_kouba group.

In the future, the 3D ED hardware setup could be extended with a hybrid pixel detector.

See more ► https://t.co/KJwFUABiO7 📲

#openposition #iocbprague #iocb

[Fusion Conferences @Fusion_Conf]

Don't forget to mark your calendars for our #RedoxBio conference, 25 - 28 May 2027.

Join leading scientists, clinicians and journal editors to explore how the regulation of multiple functions of redox biology contributes to the maintenance of cellular health and disease pathogenesis.

Click here to sign up for updates: https://t.co/ZDyWFDXBYg

[Iannis Aifantis @iannisaifantis1]

Excited to share our brand new work today @CellStemCell ...the first single-cell transcriptomic + epigenomic map of the human spleen in myelofibrosis. Using scRNA/CITE-seq + scATAC-seq from patient splenectomies, we show how the spleen becomes an aberrant niche for malignant extramedullary hematopoiesis. @NYUGSOM_Path @Perlmutter_CC
https://t.co/q1otl6QFpW

[Jan Konvalinka @konvalinka_jan]

Moc hezké shrnutí o nové protinádorové mRNA vakcíně.Jen dvě poznámky: ještě nemáme k disposici data, jen zprávu firmy; a v ČR máme nejen pracoviště, která umí navrhnout personalisované neoantigeny, ale i startup firmu s patentovanou technologiií RNA delivery (Adalid Sciences).

[Anna Vainshtein, PhD @VainshteinAnna]

A century ago, skeletal muscle was understood largely as the body’s engine. We now know that is much more vital

Our new framework in @NatMetabolism: The Hallmarks of Skeletal Muscle Health. 🧵

🔗 https://t.co/t9S3BdK3IH

#myotwitter

[Bill Ackman @BillAckman]

At midnight on February 6th, earlier this year, the doorbell to our apartment rang. The doorbell was followed by a pounding on the door. I answered the door and a security person in our building handed me his phone. It was my oldest daughter Eloise. She had found my 26-year-old daughter unconscious on the floor of her apartment and had called 911. The EMT team was already there, but they did not know what was wrong with Lucy or to which hospital they would take her.

I threw on some clothes and jumped in an Uber heading east toward Brooklyn. (Lucy lived alone in Williamsburg.) On the way, I learned that they were taking her to Elmhurst, a City trauma hospital in Queens. I arrived about five minutes after the ambulance to join Eloise, Lucy’s mom, and a friend, and waited to learn what was wrong.

After about 15 minutes, I asked a nurse where she was. I looked over his shoulder to his computer. Next to her name, it said “non-responsive.” I walked into the emergency room and wandered around looking for her until I found her unconscious on a gurney surrounded by several doctors and nurses.

By about 2:30am with the results from a CAT scan, Lucy’s doctors had determined that she had a massive brain hemorrhage and would need an emergency hemicraniectomy to release the pressure on her brain and remove the blood from the hemorrhage. I called our wonderful friend and family doctor Eddie Fisher and explained what was going on. He woke up Josh Bederson, Chairman of Neurosurgery at Mount Sinai, to find out more about Zach Hickman, the neurosurgeon on call that night. Dr. Bederson said Hickman was an excellent surgeon, which was comforting as we had no choice.

The surgery to save Lucy’s life began around 3:15am and finished around 5:30am. It was successful.

The following day, I joined Lucy in an ambulance while she was being transferred to Mount Sinai on Madison Avenue. Later that day, we determined from Lucy’s Oura ring that her hemorrhage had occurred around 9am, which meant that more than 19 hours had passed from the time of the hemorrhage to the completion of the surgery to release the pressure on her brain (I only wish @ouraring had an alert for this kind of a medical event. Imagine it could call a family member if the wearer doesn’t cancel the alert).

I later learned that the standard of care is not to do surgery to save a patient with a large brain bleed if more than five hours have passed since the hemorrhage. Even when the surgery is done, I was told that the likely outcome for the patient is a few months in a nursing home and death from pneumonia.

When I met Lucy’s doctors, I did my best to inspire them: “Let’s see what can be accomplished if we give her the best care possible and we invest unlimited resources to restore her to life.” And I promised that whatever we learned we would make available to everyone.

Dr. Chris Kellner, her neurosurgeon, and Dr. David Putrino, Director of Rehabilitation Innovation for the Mount Sinai Health System have led Lucy’s care team since that day. Words cannot describe the remarkable and compassionate care that she has received beginning with the EMT team and then from nurses, doctors, therapists, and the army of people who have worked to save her and return her to life. To this day, we have a daily Zoom where we discuss her progress and make adjustments to her care. While her care and oversight have been incredible, the learnings for the Mount Sinai team have also been elucidating and will assist in the care of many others.

Lucy began in a bad place. She was in a coma for several weeks and then awoke not being able to breathe on her own, unable to walk, see or speak.

Over the last six months, she has recovered her cognition – she understands everything including her circumstance – is able to walk a hundred or more steps at a time with assistance, is making progress with sounds, vowels and consonants and the beginnings of speech, but she remains unable to see.

Each day, she makes a little progress, and daily progress compounds. Every day I tell her that she just needs to make a little progress and it won’t be long before she is back.

We remain optimistic that Lucy will return to normal function. It will likely take years, but I believe it is only a matter of time, hard work, and technological progress, along with some, and perhaps a lot, of divine intervention.

Many people have been praying for Lucy and we are incredibly grateful for the prayers and remarkable support she has received. Lucy’s friends have been with her every day since the beginning, and their presence and friendship have saved her life and helped to rebuild and maintain her spirit. And on a very positive note, Lucy’s challenge has brought together our entire modern family who have all been incredibly devoted to her care and recovery.

Lucy's vision and other faculties may require some form of brain computer interface, work that is underway at Neuralink, Precision Neuroscience, Science, Synchron, Nudge, and other companies in the space.

If you are going to have a devastating brain injury, now is the best time in history for that to happen. We are living in a world when you can be confident that the blind will soon see again. We are going to do everything we can to help make that happen, including by assisting existing companies in the space.

With respect to our promise to make Lucy’s care available to others, we have made good progress. In May, a real estate colleague made me aware of a 93% vacant, brand new, 400,000 square foot Class A+ purpose-built biotech facility on West End Avenue between 65th and 66th Streets that missed the market and was available for sale. The Pershing Square Foundation acquired the building 60 days later.

We also put under contract an adjoining 130,000 square foot building at 320 West 66th Street that is currently being used by Saturday Night Live for studio space. The building has 35-foot ceilings with massive column-free spaces that can be converted into superb rehabilitation facilities. We will close on the SNL building in December.

We are also acquiring an adjoining vacant lot with additional air rights. With just the existing zoning rights, we can add a 150,000 square feet for a total of 680,000 square feet, a lab footprint larger than Rockefeller University, and that’s without including the potential for an upzoning that would allow for substantially more buildable area on the site’s 3.4 acres with spectacular views of the Hudson.

Our goal is to build the world’s greatest brain research, rehabilitation, recovery, human optimization, and longevity institute. We have named it The Ackman Oxman Institute or the AOI for lack of a better name, but also to reinforce the point that Neri and I and our family are all-in on the mission.

The AOI will be patient-centric. It will not be an academic research institute that produces lots of papers, a Nobel Prize winner or two, but little if any results for patients. We will be laser-focused on cures, treatments, devices, rehabilitation and exercise equipment, and targeted and basic research with a goal of massively accelerating the time from idea to innovation to production to helping a patient.

While the AOI will be a non-profit, it will have highly commercial instincts. The AOI will have its own venture funding and will work to develop innovations to create companies that we will seed, assist, and spinout to ensure technologies, treatments, techniques, and drugs get to patients as promptly as possible.

On one 3.4 acre campus in what is still the greatest city in the world, we will do neurosurgery, neuroscience, rehabilitation, nutrition, BCI and device development, human trials, hyperbaric oxygen treatments, and life extension programs, and we will mandate and incentivize collaboration among the teams with no silos, politics, bureaucracy, or any other constraint that is inconsistent with the mission.

Mount Sinai will be an important partner and deservedly so, but it won’t be our only hospital or medical school partner as we don’t believe any institution has a monopoly on the best ideas or the best talent. We don’t believe in exclusive relationships because that is not in the best interest of patients.

Five years ago, we considered launching a brain institute inspired by Neri’s mom who sadly died from Alzheimer’s. We couldn’t make the math work as the real estate was too expensive and we believed it would be too difficult to recruit the best talent from universities to our effort.

Since then, the real estate became available at a 70% discount, universities became a much less attractive place to work due to politics outweighing meritocracy, protests that disrupt learning, the curse of antisemitism, and a decline in funding. Fortunately, during the same time, I made sufficient personal economic progress to make the AOI possible.

The advance of AI in the last few years will also enable us to greatly accelerate our mission. AI still has a lot to learn about human intelligence and the brain, and the AOI should be at the forefront of the interplay between the brain and AI.

Today, I am making a public filing disclosing a gift from Neri and me of ~$400 million or 10,000,000 shares of Pershing Square Inc. (PS) to the AOI. It is very early days for Pershing Square so these shares are intended to anchor the long-term work of the AOI as the shares compound over time while generating what we expect will be a growing stream of quarterly dividends to fund the Institute.

We will also be announcing an additional gift of similar and potentially greater size which won’t be in the form of Pershing Square stock to provide the AOI with the short- and intermediate-term runway necessary to enable it to achieve its goal of becoming a self-sustaining institute, which reinvests all of its revenues, royalties, and the economic rewards of company formation to advance the fields of brain health and human longevity.

Neri and I have chosen to anchor the funding of the AOI to maintain vision alignment and limit the need for the organization to focus on fundraising. We expect the AOI to be the best-resourced brain, rehab, recovery, and longevity institute in the world.

We are grateful to have been able to form a board which includes Dean Kamen (our generation’s Thomas Edison), George Yancopoulus (CEO of Regeneron), James Rothman (Nobel Laureate), Bernardo Sabatini (neuroscientist), Chris Kellner (neurosurgeon), Olivia Flatto (CEO Pershing Square Foundation), Neri Oxman, and myself.

We have recently identified a CEO who we expect to announce by October along with other key hires, and are beginning searches for a Chief Scientific Officer, a Chief AI/Technology Officer, a Chief Operating Officer, a Chief Financial Officer, and other key leadership roles.

If you find what we are building compelling and want to be part of the leadership team that creates and builds the AOI from a standing start, please send an email to: [email protected] with a short note as to why you believe you can help. Please include your best three ideas for the AOI along with a summary of your background and your most important accomplishments.

We promise strict confidentiality to those expressing interest in working with us.

We have learned from Lucy that the brain can recover from even catastrophic injury. There is so much more work to be done as the mind is a terrible thing to waste.

For details from my Pershing Square SEC filing see:

https://t.co/gZKafCw6Ia

[Xin Gu @XinGu0317]

Think all the key pathways controlling protein homeostasis have been found? We don’t👀 The Gu Lab @DanaFarber @harvardmed is hiring postdocs, especially scientists with in vivo mouse or biochemical & structural biology expertise. Got an itch to discover something new? Join us!👇