Stuart Schreiber @SchreiberStuart Twitter profile

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Stuart Schreiber

1 month

1/4 A Perspective on proximity-inducing #molecularglues and bifunctional compounds in relation to hot-spot-associated missense mutations enshrined by natural selection and posttranslational modifications (PTMs).

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Stuart Schreiber

@SchreiberStuart

5 years

Without love and encouragement from my wife Mimi, this would have remained a personal diary for the two of us. The response from so many of you has warmed my heart. I am profoundly grateful.

DNA testing leads Stuart Schreiber to welcome answers | Harvard Magazine

A scientist discovers his own family’s secrets.

www.harvardmagazine.com

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Stuart Schreiber

@SchreiberStuart

1 year

On behalf of his loving family, and with a heavy heart, I’m sad to report the passing of Yoshito Kishi, a towering figure in organic chemistry. In addition to his transformative research, Yoshi will be forever remembered for his warmth, generosity, and deep sense of humanity.

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Stuart Schreiber

@SchreiberStuart

3 years

1/2. Molecular glues, with and without linkers, are being used to stabilize, degrade, alter cellular locations and bind otherwise featureless therapeutic targets. (Images by @moscienceart )

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Stuart Schreiber

@SchreiberStuart

3 years

In our open letter, we scientists are standing up for @Harvard professor Charles Lieber. We also are speaking out against the harm that the prosecution of Charles and other scientists has inflicted on academic freedom and scholarly collaboration.

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Stuart Schreiber

@SchreiberStuart

2 years

1/11. Molecular glues and bifunctional compounds induce neo-protein associations with target proteins and neo-substrate interactions with enzymes.

Molecular glues are beginning to stick

Researchers have already hijacked the body’s protein-disposal system with bifunctional protein degraders, or PROTACs. Small-molecule glues can do more with less—but can we find them?

cen.acs.org

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Stuart Schreiber

@SchreiberStuart

4 years

This is synthetic biology at its best – from the Pete Schultz lab at Scripps. Having made a bacterium with non-natural cross links in its cell wall, the role of this biophysical feature can now be explored in highly novel ways.

Semisynthesis of a Bacterium with Non-canonical Cell-Wall Cross-Links

The cell wall is an elaborate framework of peptidoglycan that serves to protect the bacterium against osmotic challenge. This exoskeleton is composed of repeating saccharides covalently cross-linked...

pubs.acs.org

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Stuart Schreiber

@SchreiberStuart

3 years

40 years to the day when the most remarkable and impacting event of my life occurred. Mimi and I were married. ❤️

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Stuart Schreiber

@SchreiberStuart

4 years

Today, humanity has a big aching hole in its heart. We lost a giant – Bob Williams, organic chemist extraordinaire, super-dad to his kids, loving husband to his wife and mentor to many. Bob was my mentor in life. I loved him and loved telling him so.

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Stuart Schreiber

@SchreiberStuart

4 years

Next time drug-hunter gurus tell you your idea won't work because your target is essential, have them look up this paper relating successful drug targets to "human knock-out" genes, among others. Great work by @EricMinikel and team.

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Stuart Schreiber

@SchreiberStuart

2 years

1/N. Missing, but mostly appreciating, Dave Evans (Jan 11, 1941-Apr 29, 2022). I'd like to share one remembrance. Dave was fond of saying that his first chemistry meeting in June 13-17, 1965 "changed my life". Judging from the speakers, you can easily imagine why.

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Stuart Schreiber

@SchreiberStuart

9 months

On the heels of the repurposing of FKBP12-rapamycin with a novel synthetic molecular glue (left), we now have the repurposing of cyclophilin–CsA (center) to target KRAS G12C with another synthetic glue (right)

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Stuart Schreiber

@SchreiberStuart

3 years

Half-way through my doctoral studies when my adviser passed suddenly and unexpectedly, I was rescued by a generous and outstanding mentor Yoshi Kishi. It kept me grounded and changed my life. We should all be prepared to pay forward.

Dr. Liana Lareau

@lianafaye

3 years

When a lab shuts down in the middle of your training, it can feel like the end of your career. I'm forever grateful to my mentors who were there for me in the most concrete ways. I wish trainees hit by today's news the same support and care and that they, too, land on their feet.

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Stuart Schreiber

@SchreiberStuart

3 years

Lonafarnib, a farnesyltransferase inhibitor having a novel structure, approved for treatment of Hutchinson-Gilford Progeria Syndrome.

The Progeria Research Foundation

@Progeria

3 years

Breaking news! First-ever treatment for rare rapid-aging disease #Progeria receives FDA Approval!

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Stuart Schreiber

@SchreiberStuart

6 months

1/4. Molecular glues and bifunctional compounds induce protein–protein associations. In open-source collaboration with Novartis, we first used DEL screening to discover bifunctional compounds in one step using preselected presenter and target proteins

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Stuart Schreiber

@SchreiberStuart

10 months

Screening preselected presenter (FKBP12) and target (mTOR) proteins to discover molecular glues exemplified by the discovery of a synthetic mimic of rapamycin

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Stuart Schreiber

@SchreiberStuart

4 months

Taking "induction of proximity" to a new level, Arena BioWorks, a Biomedical Research Institute that just launched in Boston, is bringing academic inquiry and biotech creation under one roof.

Arena BioWorks Launches as a Privately Funded, Fully Independent Biomedical Institute to Shorten...

Focused on determining the mechanisms of human disease and advancing new technologies to translate these insights into therapeutics through in-house biotech...

www.prnewswire.com

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Stuart Schreiber

@SchreiberStuart

5 years

Varying degrees of difficulty – yes – but it feels like it's time to retire the term "undruggable". Impossible is nothing.

Drugging an undruggable pocket on KRAS | Proceedings of the National Academy of Sciences

The 3 human RAS genes, KRAS, NRAS, and HRAS, encode 4 different RAS proteins which belong to the protein family of small GTPases that function as b...

www.pnas.org

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Stuart Schreiber

@SchreiberStuart

4 years

Well deserved – not only for transformative science but also mentorship, leadership and guidance for the nation through the pandemic under times when scientists' voices are being muted.

Harvard Chemistry

@HarvardCCB

4 years

Congratulations to David R. Liu, elected into the @theNAMedicine today for the development of base editing and prime editing to modify genomes with unprecedented precision (among other inventions): @davidrliu

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Stuart Schreiber

@SchreiberStuart

4 years

This post from @cureffi provides an illuminating analysis of the challenges of drug discovery, but also a strong argument for publishing scientific research that did not achieve its original aim. Even "failure" can advance science.

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Stuart Schreiber

@SchreiberStuart

4 years

Priscilla and Nathanael are two crown jewels of Harvard – Stanford's huge gain is a painful loss for those of us who benefited greatly from them and their awesome labs. But we love them both and wish them the very best! ❤️

Carolyn Bertozzi

@CarolynBertozzi

4 years

I am excited to announce that Nathanael Gray and Priscilla Yang are moving to @Stanford !!Nathanael will join us @Stanford_ChEMH and Dept of Chem & Sys Biol and Priscilla will join Dept of Micro & Immunol, supercharging chem bio on The Farm🔥

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Stuart Schreiber

@SchreiberStuart

3 years

Thanks @wgibson . For those who would like to read, this link provided by @CellCellPress has no paywall:

William Gibson

@wgibson

3 years

What a pleasure to read. @SchreiberStuart writes a conversational history of molecular glues, emphasizing the questions being posed at each juncture of discovery.

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Stuart Schreiber

@SchreiberStuart

4 months

This MoA will blow your mind! Amazing what small molecules are able to do. This one suggests novel future capabilities and applications.

Jonathan Ostrem

@JonathanOstrem

4 months

Excited to share our new preprint describing intracellular ubiquitination of a small molecule, BRD1732, a molecule that has remained a mystery since identification in early 2010s by Enrique Garcia-Rivera, @micahmaetani , @SchreiberStuart and @CKadoch . 🧵

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Stuart Schreiber

@SchreiberStuart

4 years

1/2. Once thought to be rare, stabilizers of protein–protein interactions now seem to be common. Two new reports of small-molecular stabilizers of specific ternary PP2A complexes and their striking effects on cell function @CellCellPress .

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Stuart Schreiber

@SchreiberStuart

2 years

NIBR ( @NovartisScience ) NLRP3 inflammasome inhibitor functions as an intramolecular glue – locking the protein in an inactive conformation !

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Stuart Schreiber

@SchreiberStuart

2 years

Congratulations to Carly Zeigler, a physician–scientist in training who gave a brilliant and inspiring lecture after receiving the inaugural 2021 Stuart L. Schreiber Award in Scientific Excellence for Graduate Students!

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Stuart Schreiber

@SchreiberStuart

5 years

A brilliant example of modern drug discovery – a small-molecule binder functioning as a molecular prosthetic to fix a disease-causing mutation ( @nchembio ). Wow!

An allosteric MALT1 inhibitor is a molecular corrector rescuing function in an immunodeficient...

Nature Chemical Biology - An allosteric inhibitor of the proteolytic activity of the CBM signalosome complex scaffolding protein MALT1 acts as a pharmacological chaperone to stabilize a mutant...

www.nature.com

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Stuart Schreiber

@SchreiberStuart

4 years

COVID-associated loss of germinal centers, responsible for long-lasting B-cell memory, suggests an additional hurdle for herd immunity and the need for avoiding SARS-CoV2 infection during attempted vaccination.

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Stuart Schreiber

@SchreiberStuart

2 years

My friend Charles Lieber gaining strength from 3-week old Opal snoozing on his lap. Goats can sense good, genuine people and trust them. ❤️

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Stuart Schreiber

@SchreiberStuart

4 years

Congratulations to Mike Rosen, co-discover of biomolecular condensates (liquid–liquid phase separation) as a widespread phenomenon in biology, for his election to the National Academy of Sciences.

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Stuart Schreiber

@SchreiberStuart

4 months

Arena follows a basic principle from physical organic chemistry: increase the effective molarity of some of the brightest minds in biomedical science, and anticipate rate acceleration

Arena BioWorks

@arenabioworks

4 months

We're proud to unveil Arena BioWorks, a biomedical research institute with a mission to uncover mechanisms of disease by engaging in basic biological research that will be translated into lifesaving #biotech therapeutics. Learn more:

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Stuart Schreiber

@SchreiberStuart

2 years

Postdoctoral training opportunity in my lab for synthetic chemists or chemical biologists to discover molecular glues and bifunctional compounds using DNA-barcoded compounds. If interested, please read and respond here:

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Stuart Schreiber

@SchreiberStuart

3 years

My sense is that protein–small molecule hybrids offer vast opportunities in medicine beyond cancer cell-killing drugs. Principles arising from bifunctional compounds, including molecular glues, can be applied to hybrids in important and novel ways. Bravo Bart Roman & @Dereklowe

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Stuart Schreiber

@SchreiberStuart

5 years

Harvard and Eisai scientists, led by Yoshi Kishi, have extended the limits of synthetic organic chemistry in drug discovery. A completely synthetic halichondrin analog E7130 is now in entering a clinical trial as a novel cancer treatment.

A landmark in drug discovery based on complex natural product synthesis

Scientific Reports - A landmark in drug discovery based on complex natural product synthesis

www.nature.com

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Stuart Schreiber

@SchreiberStuart

5 years

Lots of love for Chris Walsh today at a special event at Harvard ( #CTWalsh75 ). Chris has revealed to us the rules of chemical logic in metabolism and the nature of chemical transformations in organisms. He has transformed our field.

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Stuart Schreiber

@SchreiberStuart

4 years

1/2. A view into the future of drug discovery provided by Amgen's Ray Deshaies – with illuminating insights into multispecific drugs.

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Stuart Schreiber

@SchreiberStuart

5 years

An urgent challenge for chemistry, chemical biology and the science of therapeutics – time to get moving:

A Mysterious Infection, Spanning the Globe in a Climate of Secrecy (Published 2019)

The rise of Candida auris embodies a serious and growing public health threat: drug-resistant germs.

www.nytimes.com

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Stuart Schreiber

@SchreiberStuart

2 years

Especially for organic chemists of my generation, I hope you'll recognize the outsized yet likely underappreciated impact of a giant in our field, W. Clark Still. Thanks to @dylanvneel for this interview.

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Stuart Schreiber

@SchreiberStuart

1 year

1/2. "During a meeting with the goal of proposing a Ph.D. project, one of us (S.L.S.) had the occasion to discuss with Professor R. B. Woodward the transformation of eq 1, citing an article published in J. Org. Chem." Can you surmise the mechanism? Andy Myers did:

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Stuart Schreiber

@SchreiberStuart

10 months

Albert Eschenmoser taught us whole new ways to think about organic chemistry – from orbitals, to mechanisms, to syntheses, to life processes, and eventually even to the origins of life. His passing marks the end of an era defined by his intellectual brilliance. 💔

D-CHAB

@ETH_DCHAB

10 months

In deepest grief, the Laboratory of Organic Chemistry at @ETH_DCHAB at @ETH_en announces that our friend and colleague, Prof. em. Albert Eschenmoser passed away peacefully, at the age of 97, on July 14, 2023. Albert #Eschenmoser shaped organic chemistry as did few others. 1/3

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Stuart Schreiber

@SchreiberStuart

1 year

So many words of wisdom from Chris Walsh during his remarkable career – like this one: Chris sharing his conversation with Albert Eschenmoser regarding his reasoning of research directions during the evolution of his career: "think chemically, act biologically"

Michael Fischbach

@mfgrp

1 year

Christopher Walsh: 1944-2023 A giant indeed: the impact of his work is staggering. But Chris was even more impressive as a mentor. He was immeasurably devoted to, & loved by, his trainees. Nothing made him happier than doling out his wisdom. Superhuman & human at the same time.

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Stuart Schreiber

@SchreiberStuart

1 year

Physician–scientist in training Ally Freedy after receiving the second annual Award in Scientific Excellence at the 2022 Broad Retreat. In recognition of her discoveries chromatin biology and their potential for novel medicines. Bravo!

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Stuart Schreiber

@SchreiberStuart

5 years

Brilliant work from Brian Liau lab at Harvard showing more surprises coming from small-molecule binders – in this case from seemingly simple (they're not!) enzyme inhibitors. Follow link to must-read NCB paper. )

Harvard chemist teases out why drugs work (or don’t)

Assistant Professor Brian Liau of the Chemistry and Chemical Biology Department has answered the question of why some new drugs for acute myeloid leukemia don’t work by combining CRISPR gene editing...

news.harvard.edu

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Stuart Schreiber

@SchreiberStuart

4 years

From FKBP12-binding natural molecular glues FK506 (calcineurin) and rapamycin (mTOR), to synthetic ones like Jun Liu's rapadocin (ENT1), PROTACs and many others, we've come full circle – a new FKBP12-binding natural molecular glue WDB002 (CEP250).

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Stuart Schreiber

@SchreiberStuart

4 years

1/5. In times like these, our country has proven time and time again that we can come together and unite against a common foe (although there was never anything secretive about this particular plan).

The Wall Street Journal

@WSJ

4 years

“We may fail, but if we succeed, it could change the world.” Inside the secret plan to save America from Covid-19

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Stuart Schreiber

@SchreiberStuart

2 years

Justice League of Science Nerds (aka Scientists to Stop COVID) member "The Flash" (aka @michaelzlin )* offers insights to an alarming feature of molnupiravir – its potential to accelerate selection of harmful SARS-CoV2 variants.

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Stuart Schreiber

@SchreiberStuart

4 years

Non-natural amino acids now encoded in human hematopoietic stem cells that give rise to the entire hematopoietic system following transplantation – the Pete Schultz lab @scrippsresearch continues to advance this frontier.

Expanding the genetic code of the human hematopoietic system | Proceedings of the National Academy...

The genetic incorporation of noncanonical amino acids (ncAAs) into proteins has been realized in bacteria, yeast, and mammalian cells, and recently...

www.pnas.org

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Stuart Schreiber

@SchreiberStuart

4 years

New street murals to go with older favorites in South End–Roxbury. Exploring city art by bike with love-of-my-life Mimi is awesome therapy for a distressing 2020

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Stuart Schreiber

@SchreiberStuart

5 years

The universe of immune-cell proteins targeted by small molecules has just been expanded dramatically. Lots of exciting future directions for immune regulation.

An activity-guided map of electrophile-cysteine interactions in primary human immune cells

Electrophilic compounds originating from nature or chemical synthesis have profound effects on immune cells. These compounds are thought to act by cysteine modification to alter the functions of...

www.biorxiv.org

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Stuart Schreiber

@SchreiberStuart

4 years

With Karin Briner, Frederic Zecri, Frederic Berst, @jaybradner and colleagues @Novartis , research is underway to extend the capabilities of organic synthesis used for DNA-encoded libraries. Work led by Matthias Westphal is our most recent example. 1/n

Water-Compatible Cycloadditions of Oligonucleotide-Conjugated Strained Allenes for DNA-Encoded...

DNA-encoded libraries of small molecules are being explored extensively for the identification of binders in early drug-discovery efforts. Combinatorial syntheses of such libraries require water- and...

pubs.acs.org

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Stuart Schreiber

@SchreiberStuart

4 years

We knew melanoma resists targeted therapy and immunotherapy by adopting a high-PUFA, GPX4-dependent and ferroptosis-vulnerable cell state. Now work from @SJMorrison_ illuminates the complex role of this state (lymph vs blood) in metastasizing melanoma.

Lymph protects metastasizing melanoma cells from ferroptosis

Nature - Melanoma cells undergo less oxidative stress and less ferroptosis in lymph than in blood, owing to higher levels of oleic acid in lymph, and thus exposure to the lymphatic environment...

www.nature.com

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Stuart Schreiber

@SchreiberStuart

4 years

For your work-from-home reading list – a Perspective on the principle of high effective molarity in biology and the broad generality of bifunctional compounds that co-localize signaling proteins (molecular glues; CIPs):

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Stuart Schreiber

@SchreiberStuart

5 years

How do you uncover convergent evolution in distantly related organisms? Use small-molecule phenotypic screening of course. Ben Cravatt and team use extended lifetime to uncover connections between non-orthologous FAAH and MAGL in distant organisms.

Pharmacological convergence reveals a lipid pathway that regulates C. elegans lifespan

Nature Chemical Biology - Phenotypic screening identifies a small-molecule inhibitor of the C. elegans serine hydrolase FAAH-4 that promotes longevity and identifies the enzyme as the functional...

www.nature.com

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Stuart Schreiber

@SchreiberStuart

3 years

On this Mother's Day, I share again my love story written for my Mom. Geraldine was an uplifter who gardened the human spirit. And she was my angel.

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Stuart Schreiber

@SchreiberStuart

11 months

A tweetorial on bifunctional compounds that enable targeted protein localization with consequential rewiring of transcriptional circuitry from @Sadagopan_A and @wgibson . See also

Bifunctional small molecules that induce nuclear localization and targeted transcriptional regula...

The aberrant localization of proteins in cells is a key factor in the development of various diseases, including cancer and neurodegenerative disease. To better understand and potentially manipulate...

www.biorxiv.org

William Gibson

@wgibson

11 months

What if small molecules could allow you to alter protein localization at will? What if they could allow you to turn on specific transcription factors? Our new manuscript reveals bifunctional molecules to do just that. 🧵

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Stuart Schreiber

@SchreiberStuart

3 years

Nice summary @NatureNews on mechanisms enabling novel phage genomes to have an alternative genetic alphabet – what commentator Steve Benner colorfully describes as “a shadow biosphere”.

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Stuart Schreiber

@SchreiberStuart

11 months

🙏

IKCOC-15→16

@15Ikcoc

11 months

We are thrilled to announce that the 5th IKCOC prize goes to the pioneer of chemical biology, Professor Stuart L. Schreiber ! @SchreiberStuart #ikcoc15

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Stuart Schreiber

@SchreiberStuart

6 months

When Ono recognized that Opdivo (nivolumab) was becoming a blockbuster, instead of searching for profit-expanding devices, they created the Ono Pharma Foundation and its Breakthrough Science Initiative Awards. Proud to have helped identify next-generation chemical biology stars

ONO PHARMA FOUNDATION

@OnoPharmaFound

6 months

Dr. Stuart Schreiber @SchreiberStuart , Chair of Science Advisory Board, has stepped down from his role. We want to express our heartfelt gratitude for his invaluable contributions and unwavering dedication. 1/5

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Stuart Schreiber

@SchreiberStuart

2 years

12/N. The elegance of Dave and his research is embodied in ChemDraw, which he and his wife Sally helped envision and create, and his recognition that combined with the Macintosh computer the way we teach organic chemistry would be forever changed. ❤️

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Stuart Schreiber

@SchreiberStuart

10 months

Dear E.J., "May your hands always be busy May your feet always be swift May you have a strong foundation When the winds of changes shift May your heart always be joyful May your song always be sung May you stay forever young" Bob Dylan, 1973 Happy Birthday! Love, Stuart

Lives in Chemistry

@livesinchem

10 months

🎁HBT #chemistry #NobelLaureate 1990 E. J. Corey turning 95 today. PhD with J. C. Sheehan @MITin 1951; faculty member @UofIllinois , full professor at age 27. In 1959 he moved to @HarvardCCB where he has been ever since, still active prof. em. He educated over 700 group members,

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Stuart Schreiber

@SchreiberStuart

4 years

"I fear I’m going to take this ML210 mystery to my grave’,” but “Like peeling the many layers of an onion, Jake has revealed, the fascinating sequence of chemical reactions that cells confer on ML210. It was a brilliant job of molecular sleuthing by Jake.”

Chemical mystery solved: Researchers discover molecule’s unusual cell-killing mechanism

The surprising transformation of a compound into a cancer killer suggests potential new ways to treat drug-resistant tumors

www.broadinstitute.org

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Stuart Schreiber

@SchreiberStuart

9 months

Boston has many hidden gems. Across from Faneuil Hall is a nondescript gate on North St labeled Scott's Alley. The alley was built in 1654 by Joshua Scottow to connect to his eponymous Dock, a harbor to park ships. The misnamed alley is still standing with little alteration.

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Stuart Schreiber

@SchreiberStuart

5 years

Deeply inspired by Herbert Waldmann at the MIT-Broad Chemical Biology Lecture Series. Creative synthetic chemistry combined with innovative phenotypic screening yielding novel probes. And our learning continued late into the night!

Chemical Biology at the Broad Institute

@Broad_ChemBio

5 years

We very much enjoyed Professor Herbert Waldmann's lecture on leveraging the power of nature to design natural product-like small molecules with biological activity. Another great joint @ChemistryMIT and @broadinstitute seminar today! #chemtwitter #chemicalbiology #chembio

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Stuart Schreiber

@SchreiberStuart

2 years

1/6. A true and illuminating testimonial of a remarkable scientist and citizen, Charles Lieber, who has dedicated his life to fundamental academic research in the fields of chemistry and nanotechnology, and to teaching students from around the world.

The Charlie Lieber we know

Kang-Kuen Ni and I (Dan) are writing because the Charlie Lieber we know is not the person you have been hearing about in the news. Charlie…

medium.com

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Stuart Schreiber

@SchreiberStuart

5 years

Another reminder ( @Nature ) of the need to balance big science and deep science. We all still have a ways to go:

Large teams develop and small teams disrupt science and technology

Nature - Analyses of the output produced by large versus small teams of researchers and innovators demonstrate that their work differs systematically in the extent to which it disrupts or develops...

www.nature.com

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Stuart Schreiber

@SchreiberStuart

3 months

Conformational analysis of ten-membered rings in the context of drug discovery. This is at the heart of what brought many of us to the beautiful science of organic chemistry.

Dr Bethany Halford

@beth_halford

3 months

Andy Myers's and Yury Polikanov's labs have come up with a new resistance-defying antibiotic called cresomycin. My latest on the work for @cenmag

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Stuart Schreiber

@SchreiberStuart

4 years

I'm so grateful, and so looking forward to catching up with friends and colleagues in Bordeaux

Société de Chimie Thérapeutique

@SCT_asso

4 years

Le prix Paul Ehrlich 2020 a été attribué au Prof. Stuart L. SCHREIBER. Il lui sera remis lors des RICT 2020 à Bordeaux 1-3 juillet @reseauSCF @SchreiberStuart @NiceChemistry #prixEhrlich #MedicinalChemistry #ChemicalBiology #Soci étéChimieThérapeutique

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Stuart Schreiber

@SchreiberStuart

4 years

ACS Chem Biol Lectureship Award extends its tradition of selecting the very best – congratulations David Liu!

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Stuart Schreiber

@SchreiberStuart

3 months

Years ago, the birth of a biotech might be chronicled in a book – such as Vertex in the "The Billion-Dollar Molecule". Today, young entrepreneurs can gain insights via Podcasts. This is an illuminating series telling the story of the birth of Belharra Tx.

Belharra: The Birth of a Biotech Podcast | Belharra

Ever wondered how a brilliant scientific idea is transformed from lab findings to a new biotech start-up…and eventually to new medicines that can impact millions of patients’ lives? In this podcast,...

birthofabiotech.podbean.com

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Stuart Schreiber

@SchreiberStuart

4 years

Now, even our scientific journals fail to provide an honest, truthful narrative – instead we see misogynistic and racist rants. Shame on the journal and the author. Thanks to @MJCliffe for preserving a link:

[email protected]

drive.google.com

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Stuart Schreiber

@SchreiberStuart

4 years

Meet freshly minted Harvard Ph.D., Dr. Bruce Hua. Bruce earned his degree by executing on his brilliant insights into organic synthesis and chemical biology. What emerged was a doctoral thesis for the ages. Bravo!

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Stuart Schreiber

@SchreiberStuart

1 year

1/2. Lots of mysteries surrounding glue mechanisms, so its nice to see hydrophobic shielding of hydrogen bonds highlighted here by @Dereklowe . I'll bet there will be other surprises uncovered in the future.

How Glues Do the Gluing

www.science.org

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Stuart Schreiber

@SchreiberStuart

3 years

Keep an eye on applications of this promising tool compound from Brian Liau @HarvardCCB for mapping ribosome positions on mRNA genome-wide (ribosome profiling) and other chemical biology applications underway @liaulab .

Discovery of C13-Aminobenzoyl Cycloheximide Derivatives that Potently Inhibit Translation Elongation

Employed for over half a century to study protein synthesis, cycloheximide (CHX, 1) is a small molecule natural product that reversibly inhibits translation elongation. More recently, CHX has been...

pubs.acs.org

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Stuart Schreiber

@SchreiberStuart

3 years

1/n. Many of us in the scientific community are heartbroken by the sudden and tragic loss of Daniela Gerhard, a brilliant and inspirational scientist at the National Cancer Institute. But Daniela was much more than that, as I hope to share in this thread.

DANIELA GERHARD Obituary (1953 - 2021) - New York, NY - New York Times

View DANIELA GERHARD's obituary, send flowers and sign the guestbook.

www.legacy.com

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Stuart Schreiber

@SchreiberStuart

2 years

The world mourns with you and your family @barneygrubbs . Your dad was an inspiration to many – for his profound impact on chemistry but even more for his warmth, natural kindness and humanity. 💙

Barney Grubbs

@barneygrubbs

2 years

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Stuart Schreiber

@SchreiberStuart

5 years

Basic biology (senescent cells upregulate beta-Gal) meets basic organic chemistry (unleash a critical cell-killing functionality by hydrolysis) to yield an ingenious targeted senolytic agent. Bravo!

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Stuart Schreiber

@SchreiberStuart

4 years

Bill Haseltine is an unflappable straight shooter – worth listening to here regarding HCQ (and by implication HCQ/AZ combination)

Lis Power

@LisPower1

4 years

Fox anchor: Can you tell me your thoughts on the drug that is used normally to treat malaria. Dr. Haseltine: It's sad to me that people are promoting that drug. Anchor: But what about the anecdotal evidence? Haseltine: That's complete and utter nonsense. Irresponsible.

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Stuart Schreiber

@SchreiberStuart

29 days

Human genetic evidence for target relevancy increases the probability of success in clinical trials, and there is still more room for improvement in the future – insights from Eric Minikel et al.

Eric Vallabh Minikel

@cureffi

1 month

Published today, our reasons for optimism that success rates in drug discovery can be improved by picking the right targets using human genetics: I break the key findings down panel by panel in this thread:

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Stuart Schreiber

@SchreiberStuart

4 years

Note the striking difference of humidity on clearance – not a big extrapolation to SARS-CoV2. Time to humidify our schools, homes and work spaces.

Prof. Akiko Iwasaki

@VirusesImmunity

4 years

As we approach the cold winter months in the Northern Hemisphere, I want to share these movies of mucociliary clearance (MCC) in the trachea of mice housed at 10% vs. 50% relative humidity (RH). Captured by @ericsongg (1/n) This is MCC at 50% RH 👇🏽

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Stuart Schreiber

@SchreiberStuart

2 years

How do molecular glues become unglued? By a powerful and general method from @brian_b_liau

Profiling the Landscape of Drug Resistance Mutations in Neosubstrates to Molecular Glue Degraders

Targeted protein degradation (TPD) holds immense promise for drug discovery, but mechanisms of acquired resistance to degraders remain to be fully identified. Here, we used clustered regularly...

pubs.acs.org

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Stuart Schreiber

@SchreiberStuart

4 years

Another thoughtful reminder of the need to balance big science and deep science, this time from Bill Kaelin:

Opinion | Why we can’t cure cancer with a moonshot

Cancer is a scientific challenge, not an engineering challenge. The difference is huge.

www.washingtonpost.com

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Stuart Schreiber

@SchreiberStuart

8 months

Congratulations Jin-Quan Yu!

Yulab

@YulabJin

8 months

Presenting my 20 year progress on enantio CH activation in front of my mentor Professor Corey, and teacher Eric Jacobsen who taught me organometallic class then. Photo 1 siting next to my mentor getting ready; photo 2 feeling spoiled when Eric presented the Tishler Prize medal.

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Stuart Schreiber

@SchreiberStuart

4 years

Finally – we got the answer to the obvious question: Why not solve our University's financial woes by dipping into its massive endowment (rather than undertaking painful layoffs and hiring freezes)? Thanks @StearnsLab for the enlightenment.

Tim Stearns

@StearnsLab

4 years

Brilliant: The. Endowment. Is. Not. For. You.

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Stuart Schreiber

@SchreiberStuart

4 years

Charles Lieber is a high-integrity and brilliant scientist, amazing colleague, loving father and husband – and a fighter.

Scientist Accused of Hiding Chinese Funds Sues Harvard, Saying It Abandoned Him (Published 2020)

Charles M. Lieber, the chair of Harvard’s chemistry department, claimed in the lawsuit that the university turned its back on a “dedicated faculty member.”

www.nytimes.com

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Stuart Schreiber

@SchreiberStuart

3 years

2/2. I hope the history and future promise are captured in a readable way here, especially for students who want a glimpse into the pre-Internet era! (P.S. my second attempt at providing a paywall-free link – sorry for my previous failure)

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Stuart Schreiber

@SchreiberStuart

4 years

Meet the Justice League of Science Nerds starring, among others, @davidrliu as Cyborg, Ben Cravatt as Batman, Akiko Iwasaki/ @VirusesImmunity as Wonder Woman, @michaelzlin as The Flash, and Ramnik Xavier as Superman! Thanks to @realrobcopeland @WSJPodcasts .

The Wall Street Journal

@WSJ

4 years

🎧 Listen: In today's episode of The Journal podcast, @realrobcopeland explains how some of America’s top scientists are working to come up with ideas to combat the pandemic and collaborating with investors to get those ideas to the White House

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Stuart Schreiber

@SchreiberStuart

4 years

I meant to include this photo in my "1980s Camelot" tribute to Sam Danishefsky () but was unable to locate it. Well, here it is, better late than never (how many faces can you recognize?).

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Stuart Schreiber

@SchreiberStuart

5 years

Great to see the structural capstone of Dan Kahne's brilliant biochemical dissection of bacterial export of LPS to the outer membrane – confirming his membrane-to-membrane Pez model. Seeing is believing!

Structural basis of unidirectional export of lipopolysaccharide to the cell surface

Nature - Crystal structures of a five-protein complex comprising the inner-membrane components of the bacterial lipopolysaccharide transporter provide insight into the mechanism of extraction of...

www.nature.com

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Stuart Schreiber

@SchreiberStuart

2 years

For Ben Cravatt's deep functional analysis of the proteome using innovative chemical methods – well deserved!

Xin Jin, PhD

@xinjin

2 years

Celebrating Ben Cravatt as the 6th Wolf Prize winner at @scrippsresearch chemistry. He and his team turned ‘dirty’ covalent compounds into transformative tools e.g. activity based protein profiling. Party coincides with grad recruit dinner-Ben was a Scripps grad student! 😉

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Stuart Schreiber

@SchreiberStuart

5 years

Koji was a man who fell to Earth, sent here to inspire us.

Koji Nakanishi dies at age 93

Natural products chemist isolated more than 200 biologically active compounds.

cen.acs.org

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Stuart Schreiber

@SchreiberStuart

2 years

Creative chemistry driving probe and drug discovery – congratulations Damian!

BlackInChem

@BlackInChem

2 years

Today we embrace Dr. Damian Young, who is a medicinal chemist, and the Assistant Professor of Pharmacology and Chemical Biology at Baylor College of Medicine where his lab focuses on fragment based drug discovery. #Blackinchem #chemistry #blackchemists #STEM #blackandstem

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Stuart Schreiber

@SchreiberStuart

5 years

Made my weekly visit to my sweet Cajun Mom's paver in the Rose Kennedy Parkway. Lots of tears, lots of joy. "I miss you Mom, my angel and protector. For you, the well of love in my heart is endless. Happy Mother's Day.❤️"

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Stuart Schreiber

@SchreiberStuart

1 year

A molecular glue approach to slowing aggressive leukemia from Christina Woo @drcmwoo lab via @Harvard

New approach to slowing aggressive leukemia — Harvard Gazette

Compounds that degrade proteins and block cell growth developed by Harvard researchers hold promise as a treatment for more types of cancer.

news.harvard.edu

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Stuart Schreiber

@SchreiberStuart

5 years

Remember to determine your protein target's interactome following small-molecule binding in cells – here's another fascinating example!

Angewandte Chemie

@angew_chem

5 years

Inhibitor-Induced Dimerization of an Essential Oxidoreductase from African Trypanosomes (Hellmich)

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Stuart Schreiber

@SchreiberStuart

5 years

Small-molecule regulation of phase separation is a promising mode of therapeutic intervention, and this new role for the druggable HDAC6 @nchembio appears to provide at least one avenue forward.

Acetylation of intrinsically disordered regions regulates phase separation

Nature Chemical Biology - HDAC6 modulates acetylation at multiple lysine residues in the N-terminal intrinsically disordered region of RNA helicase DDX3X to regulate liquid–liquid phase...

www.nature.com

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Stuart Schreiber

@SchreiberStuart

6 months

Rewiring transcriptional circuitry with a bifunctional compound!

William Gibson

@wgibson

6 months

Our work describing targeted protein relocalization and transcriptional rewiring is now out in @J_A_C_S !

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Stuart Schreiber

@SchreiberStuart

1 year

@JSheltzer Trikafta: a combination of three intramolecular glues that stitch domains together synergistically to complement missing biophysical and cellular functions in disease alleles (Karol Fiedorczuk, Jue Chen, et. al, Science 2022).

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Stuart Schreiber

@SchreiberStuart

3 years

Cells can adopt stable cell states that avoid apoptotic death (e.g., drug-resistant cancers; fibrotic tissues; activated immune cells), but the mechanism for doing so creates a ferroptotic vulnerability. Kojin is addressing this gap in current pharmacopeia.

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Stuart Schreiber

@SchreiberStuart

5 years

Three Amigos

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Stuart Schreiber

@SchreiberStuart

4 years

Bifunctional, proximity-inducing small molecules facilitate the study of an increasingly wide range of complex biological phenomena. Now, in 2 reports, they enter the KRAS arena – 1) reanalysis of previously reported binders:

The small molecule BI-2852 induces a nonfunctional dimer of KRAS | Proceedings of the National...

The small molecule BI-2852 induces a nonfunctional dimer of KRAS

www.pnas.org

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