Lara K. Mahal

Discovery, Optimization, and Anticancer Activity of Lipid-Competitive Pleckstrin Homology Domain-Containing Family A Inhibitors Phosphoinositide signaling is a major cellular mechanism controlling cancer cell viability, proliferation, and survival. Yet, inhibition of lipid kinases that produce oncogenic phosphoinositides has afforded only a limited number of efficacious drugs attributed in large part to on-target toxicity resulting from the pleiotropic effects of these signaling lipids. Targeting the specific phosphoinositide effector pathways via competitive inhibitors of phosphoinositide-recognizing pleckstrin homology (PH) domains represents a relatively unexplored means to achieve greater specificity. Herein, we present the discovery from in silico screening, structure–activity relationship (SAR) optimization, and cellular characterization of novel phosphoinositide-competitive inhibitors of the pleckstrin homology domain-containing A (PLEKHA) family. These compounds induce cytotoxic effects in BRAF and NRAS mutant melanoma cells, consistent with on-target inhibition, and the most potent compound is activated by endogenous esterase activity, suggesting that prodrug esters represent a viable strategy for targeting the phosphoinositide-binding pockets of the PLEKHA family of PH domains.

A while back we found that the lipid-binding protein PLEKHA4 boosts Wnt/β-catenin signaling and drives melanoma growth in vivo. Now, we (Nathan Frederick) identify small-molecule inhibitors of PLEKHA4 & related proteins with anticancer activity in vitro! pubs.acs.org/doi/10.1021/....

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8️⃣8️⃣ Frances Oldham Kelsey (1914-2015) 🇨🇦 #womeninSTEM Canadian pharmacologist and physician, FDA expert who refused marketing authorization for thalidomide in the USA because she felt its safety had not been demonstrated.

thecanadianencyclopedia.ca/en/article/f...

Roxana Halls,
Laughing While Conducting - Fan, 2022,
contemporary UK painter #WomensArt

Postpartum haemorrhage is one of the leading causes of maternal mortality globally.

Even when not fatal, it can lead to lifelong physical and mental health impacts, from major organ damage to hysterectomies, anxiety and trauma.

It is highly treatable if caught early

#glycotime

GIA2025 Join us for our fourth annual symposium, a celebration of knowledge and innovation in the field of glycoscience! Whether you’re an aspiring scientist or a seasoned researcher…

We’re excited to invite you to the @giaglyco.bsky.social GIA2025 Symposium on Thursday and Friday, November 6–7. Registration is free and the event will take place in person and virtually for those joining online. glyco-alberta.ca/gia2025/ Come get the latest #Glycogang swag!

AI ate my homework: My experience with the University’s AI toolkit I don’t understand AI enough to properly dislike it. And I’m curious as to why the University is pushing this tool so much if it inherently devalues learning. So I immersed myself in artificial intell...

The students get it. www.michigandaily.com/statement/ai...

Print in orange and brown hurs featuring a curked up fox looking out towards the viewed while lying among autumn leaves

'Protected' by Yorkshire born printmaker Hester Cox.
#ReframingWomenPrintmakers

Proud of these kids standing up to bullies.

NSF Graduate Research Fellowship Program (GRFP)

🚨GRFP DEADLINE ALERT!🚨 I missed this in my original solicitation read-through, so FYI 📣LETTERS ARE DUE BEFORE PROPOSALS📣 this year!

"Reference letters are due Friday, November 7 at 5:00 p.m. Eastern Time (ET)."

www.nsf.gov/funding/oppo...

Climate-linked escalation of societally disastrous wildfires Climate change and land mismanagement are creating increasingly fire-prone built and natural environments. However, despite worsening fire seasons, evidence is lacking globally for trends in socially ...

Out today in @science.org, we show wildfire disasters have surged in the last decade, as climate change intensifies fire weather and exacerbates other vulnerabilities.

📄 www.science.org/doi/10.1126/...

With @pyrogeog.bsky.social @climate-guy.bsky.social

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A mural of Octavia Butler, a Black woman in a red shirt and short hair, looking up. Next to her, trees and a street sign saying “Octavia Butler Ave.” And a note that: “Octavia Butler (1947-2006) lived in Lake Forest Park from 1999 until her death. In 2023 the city named a street after her in recognition of her many contributions to the world of science fiction.”

I gotta say I think it’s cool we have a mural up in town to honor the awesome Octavia Butler, who lived car-free in LFP.

“Many contributions to science fiction” sells her short, but writing captions always means omitting context.

PubMed is in trouble

This is beyond bad for medical research

pubmed.ncbi.nlm.nih.gov

On the left - western blot of B16F10 cells wt and KO for CDK8. Our in house produced antibodies give a lot of unspecific bands. On the right same probes with antibodies preincubated with fixed CDK8 KO cells - there is a specific band and faint unspecific bands, which can be probably eliminated with increase of amount of KO cells.

Neat trick if you polycolonal ab's suck. Incubate them with fixed cells with a KO of your protein of interest, then spin. Protocol here: www.med.upenn.edu/markslab/ass...
I was amazed how well it worked on first try (I'm sure that I can completely eliminate unspecific bands)
#WesternBlot #cellsky

Meet the determined woman who invented duct tape The iconic product has been around for 75 years. Learn about the "aha" moment that sparked the idea for its creation, the U.S. president who pushed it forward—and how Johnson & Johnson helped bring it...

When Vesta Stoudt, munitions worker, wrote to FDR about paper-backed tape used to waterproof munitions box.
The paper tabs could tear, making the boxes difficult to open in combat.

FDR directed Revolite Corporation (now J&J) to make the tape she proposed: cloth-backed, plastic-coated.

A real triumph for #glycotime and basic research, thanks to the work of Steve Withers and others.🧪

No increase in birth defects found following COVID vaccination in pregnancy

Here's the study I pointed out here on @bsky.app during the ACIP meeting. It is a large Scandinavian study of 343,066 infants. Maternal vaccination in the first trimester was not associated with increased risk of congenital anomalies via @cidrap.bsky.social.

www.cidrap.umn.edu/covid-19/no-...

The death of the premature baby born after their mother contracted measles highlights the danger of more and more people refusing vaccines.

An individual is contagious 4 days before the rash appears.

Imagine a child with measles at a daycare full of babies too young to be vaccinated.

Congratulations!🎉

A powerful statement by the Dave Mathews Band on the passing of Dr. Jane Goodall.
"Hope is an act of resistance when the world is run by cruelty and greed"

Macarena Toll-Riera (IBE): a lifetime studying evolution - El·lipse In this interview, Macarena Toll-Riera, head of the evolutionary microbiology group (IBE: CSIC-UPF), explains her path to the field of evolution.

Meet Macarena Toll-Riera, group leader at @ibe-barcelona.bsky.social , whose passion for #evolution led her from Zürich back to @prbb.org 

👉In our interview she shares insights on #WomenInScience, #Sustainability & research challenges

Have a read!👇 
https://tuit.cat/pbPgm

#PRBBcommunity

Spatial mapping of cell-surface protein glycosylation at molecular resolution Cell-surface protein glycosylation is a fundamental post-translational modification that plays a crucial role in membrane protein function and cellular behavior. However, elucidating the molecular spa...

NEW PREPRINT: Spatial mapping of cell-surface protein glycosylation at molecular resolution 🍭🍬🔬
For the first time, we can analyze the spatial architecture of the cell-surface glycoproteome at single-protein and single-sugar resolution. #glycotime

www.biorxiv.org/content/10.1...

Jane Goodall, renowned chimpanzee researcher and animal advocate, dies at 91 "Dr. Goodall's discoveries as an ethologist revolutionized science, and she was a tireless advocate for the protection and restoration of our natural world," the Jane Goodall Institute said in a Wedne...

Sad to read Jane Goodall has died. She inspired a whole generation of biologists and conservationists. Read my first book by her in high school. We also happen to share a birthday😊. An absolute LEGEND, the world is lucky to have experienced her talent and compassion.
www.nbcnews.com/news/obituar...

Long Covid Risk for Children Doubles After a Second Infection, Study Finds

1/
"Children and teenagers are twice as likely to develop #LongCOVID after a second coronavirus infection as after an initial infection, a large new study has found":

www.nytimes.com/2025/09/30/h...

RSV vaccines offer vital protection for the most vulnerable, study confirms A review of 14 clinical trials involving more than 100,000 participants supports widespread RSV vaccination to reduce severe illness and hospitalisations.

A new Cochrane review pooled >100,000 participants across 14 trials of RSV vaccines:
- In older adults,RSV vaccines ⬇️ RSV-related lower resp illness by ~70%.
- In pregnant people, vaccination halved the risk of infants needing medical care for RSV & ⬇️severe dz by ~74%.
www.gavi.org/vaccineswork...

MW correctly reading the room

Frances H. Arnold forges ahead The 2025 Priestley Medalist directs her own evolution

ICYMI: C&EN spoke with the busy Nobel laureate and Priestley Medalist about her days as a rebellious teenager, her life as a leader in biochemical engineering, and her time serving her country. cen.acs.org/people/award... #chemsky 🧪

YouTube video by Black In Biophys BIBPSSpotlight - 2025 Black In Biophysics Week

We are in this odd climate where people are pretending no barriers exist to careers in science for some groups, but this conversation with 2 outstanding emerging scientists highlights that is just not true.
youtube.com/watch?v=u850...