Oncogenic Signaling Shaped by a Golgi Trafficking Protein Pair

A new study in Science Signaling identifies a previously overlooked control point in receptor tyrosine kinase (RTK) signaling, one that operates not at the plasma membrane, but at the Golgi. The research, published as “Oncogenic receptor tyrosine kinase signaling is driven by the Golgi protein GOLPH3 and its interaction with MYO18A,” reveals that the Golgi‑localized proteins GOLPH3 and MYO18A act together to route RTKs to the cell surface, thereby setting the strength of growth‑factor signaling across multiple pathways.

The work was led by Kyle Starost and colleagues at Case Western Reserve University School of Medicine and the University of California, San Diego. Their findings help explain why GOLPH3 is frequently amplified in human cancers and why its overexpression correlates with poor prognosis across tumor types.

RTKs such as EGFR, insulin receptor, and PDGFR are central drivers of proliferation and survival in many cancers. Although RTK inhibitors are widely used clinically, resistance often emerges, underscoring the need for alternative strategies that modulate signaling upstream of the receptor. The new study identifies one such upstream node: the delivery of RTKs from the Golgi to the plasma membrane.

Using an unbiased signaling analysis, the team found that siRNA knockdown of GOLPH3 or MYO18A impaired phosphorylation of EGFR at Tyr1068 and Tyr1086, as well as downstream AKT and ERK signaling. These defects persisted even when PI3K/AKT/mTOR signaling was pharmacologically blocked, demonstrating that GOLPH3 acts directly at the receptor level rather than through mTOR modulation.

To pinpoint the mechanism, the researchers turned to trafficking assays. Imaging of endogenous EGFR showed that loss of GOLPH3 or MYO18A caused the receptor to accumulate in intracellular puncta rather than at the plasma membrane. A quantitative PDGFR‑GFP surface‑delivery assay confirmed that both proteins are required for Golgi‑to‑surface transport. Treatment with brefeldin A or golgicide A, which disrupt Golgi structure, produced similar reductions in surface receptor levels, reinforcing the conclusion that the GOLPH3–MYO18A complex is essential for RTK delivery.

Overexpression experiments completed the mechanistic picture. Increasing GOLPH3 or MYO18A levels enhanced EGF‑stimulated phosphorylation of EGFR and AKT, while a GOLPH3 mutant unable to bind PI4P failed to do so. These results position the GOLPH3–MYO18A complex as a central determinant of RTK availability at the cell surface.

The authors wrote, “The GOLPH3-MYO18A complex at the Golgi apparatus was required and rate-limiting for RTK signaling across the cell types and receptors assessed.” The findings suggest that targeting Golgi‑based trafficking machinery could offer a new therapeutic angle for tumors that rely on hyperactive RTK signaling or have developed resistance to RTK inhibitors.

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Trump’s cuts to foreign aid are undermining the Ebola response, insiders say

WASHINGTON — For years, the United States has poured hundreds of millions of dollars into programs to prevent and control infectious diseases in the Democratic Republic of the Congo.

But in the months leading up to a fast-moving Ebola outbreak, the Trump administration slashed aid to the country, leading to a cascade of consequences that probably hampered the detection of the outbreak and the response to it, six people involved in or familiar with the efforts in the region said. 

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Mobile App–Based Smoking Cessation in Hispanic or Latino Adults: Culturally Tailored Spanish-Language Formative App Development Study

Background: Despite the notable proliferation of smoking cessation mobile apps, to date, no validated, Spanish-language, culturally tailored mobile intervention exists for Spanish speakers in the United States. Objective: The aim of this study was to conduct formative research to inform the adaptation of an evidence-based smoking cessation intervention developed for Spanish-speaking Hispanic and Latino individuals from a printed format into a mobile app. Methods: Guided by a user-centered approach and in collaboration with product design industry experts, wireframes were developed to present the app’s layout and functionality. Focus groups were conducted over Zoom (Zoom Communications) with Spanish-speaking individuals who currently smoke to assess their previous mobile app experience, attitudes toward mobile apps, and feedback on app architecture and design. Two independent reviewers (RB in collaboration with another member from the qualitative core) trained in qualitative methods coded the focus group data using a thematic analysis approach and identified emerging themes. Results: The app wireframes included 4 navigation buttons on the home screen to organize and deliver evidence-based intervention content—Home (), Learn (), My Coach (), and Profile (). Different wireframe designs were generated in distinct color palettes. Data saturation was reached after three focus groups. Participants were 54% (7/13) women, had a mean age of 56 (SD 14.9) years, 39% (5/13) had an education ≤high school, and 31% (4/13) were married or cohabitating. All participants smoked daily, a mean of 14 (SD 7.8) cigarettes per day, for 32 (SD 16.9) years, and 54% (7/13) smoked ≤30 minutes of waking. Participants reported using social media, news, shopping, and gaming apps, but few used mobile health apps. Salient barriers for app use included worries regarding privacy breaches and fears about misinformation. Desired features included community-building elements, personalization, reward badges, knowledge checks, and audiovisual presentation of content within the app. Participants disliked having a countdown to quit date, preferring an “I quit” button to initiate monitoring progress. They also viewed sharing progress with support networks as a source of unwanted pressure, although a few saw it as motivational. Overall, participants liked the app design and indicated willingness to use it. Conclusions: This formative research provides critical insights into preferences related to the development of culturally tailored mobile smoking cessation interventions for Spanish-speaking individuals. Key findings highlighted enthusiasm for a smoking cessation app and the importance of including features that foster social connection and allow for personalization.
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STAT+: Virginia governor vetoes legislation to create an advisory panel to lower the cost of prescription drugs

Virginia Gov. Abigail Spanberger has vetoed closely watched legislation to create an advisory panel to lower prescription drug costs, a setback to attempts by lawmakers across the United States to address the rising cost of medicines.

Unlike affordability boards in other states, the Virginia panel would have used Medicare as a benchmark. Rather than start from scratch to identify drugs considered expensive, each year the panel would have targeted the same drugs chosen by Medicare for price negotiations. The board would have also set upper payment limits to create a ceiling on what would be paid.

By doing so, Virginia would have leapfrogged plans by other states that are at varying stages of establishing affordability boards. Of the other nine states that have boards, none is eyeing all of the same drugs chosen annually by Medicare and only four have the authority to set upper payment limits.

Continue to STAT+ to read the full story…

STAT+: 1 in 8 women drink during pregnancy. Experts dread the consequences

The idea of drinking during pregnancy sounds like a generational punchline: Someone’s grandmother drank beer to fatten her fetus, another had a nightly martini to get a healthy amount of sleep — presumably unthinkable behavior in today’s America. 

Yet after precipitous declines in the last 50 years, rates of alcohol use in pregnancy in the U.S. started climbing upward a decade ago. More than 1 in 8 pregnant adults reported drinking in the past month, according to STAT’s analysis of 2024 government data, making alcohol use a more common national phenomenon than gestational diabetes. Of those who drank, a quarter reported having four or more drinks in one sitting — binge drinking — in the prior month. 

While rates of alcohol use in pregnancy are lower in the U.S. than those of several peer nations, the effects are all around Americans. Alcohol is the key driver of what are, by some estimates, the nation’s top neurodevelopmental conditions: fetal alcohol spectrum disorders, or FASDs.

The exact prevalence of FASDs is difficult to measure, but the most recent federally funded community studies have found as many as 1 in 20 school-aged children may have a disorder caused by prenatal alcohol exposure. By comparison, about 1 in 31 American children has autism, per recent estimates from the Centers for Disease Control and Prevention.

Not all fetuses exposed to alcohol have birth defects or go on to develop intellectual disabilities, researchers say. But every person born with an FASD was harmed by alcohol specifically. They worry this point is being glossed over as Americans question the conventional medical advice of avoiding all alcohol while pregnant.

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Opinion: Britain embraces a Massachusetts experiment on tobacco regulation — just as the state might roll it back

The United Kingdom just adopted a tobacco-free generation law. Retailers can still sell tobacco to existing customers, but they will never be permitted to sell it to anyone born after Jan. 1, 2009.

In Massachusetts, 24 communities already use a similar “nicotine free generation” (NFG) birthdate phaseout of tobacco sales, including cigarettes, vapes, and pouches. What seemed to some an oddball local experiment here has become the leading edge of a public health revolution. Britain adds 69 million people to the 659,000 Massachusetts residents protected by this tobacco endgame.

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Here’s why Elon Musk lost his suit against OpenAI

On Monday, the jury in Musk v. Altman dealt Elon Musk a major blow—reaching a unanimous advisory verdict that he had sued OpenAI too late and, as a result, his claims are barred by the applicable statutes of limitations. US District Judge Yvonne Gonzalez Rogers immediately accepted it. 

Musk announced on X that he will be appealing the decision. “The judge & jury never actually ruled on the merits of the case, just on a calendar technicality,” he wrote.

OpenAI was cofounded by Musk and a group of researchers in 2015 as a nonprofit with a mission to develop AI for the benefit of humanity, unconstrained by a need to generate financial returns. Musk donated $38 million to the company during its early days, allegedly on the basis that OpenAI CEO Sam Altman and president Greg Brockman had promised to keep the company a nonprofit committed to the mission.   

Musk brought two claims against OpenAI. First, he argued that Altman and Brockman breached the charitable trust he created through his donations by breaking their promise to keep the company a nonprofit and creating a for-profit subsidiary that ballooned over the years. Second, he argued that Altman and Brockman unjustly enriched themselves at Musk’s expense. He sued OpenAI in 2024. 

Musk asked the court to unwind a 2025 restructuring that converted OpenAI’s for-profit subsidiary into a public benefit corporation and to remove Altman and Brockman from their roles.

OpenAI argued that the time for Musk to sue the company had run out before he brought the case. The statute of limitations on the breach of charitable trust claim is three years, while the statute of limitations on the unjust enrichment claim is two years. This means that Musk should have discovered, or had reason to discover, Altman and Brockman’s alleged breach of charitable trust no earlier than 2021 and their alleged unjust enrichment no earlier than 2022. 

While Musk argued he discovered that Altman and Brockman had broken their promise only in 2022, OpenAI claimed that Musk had reason to think this well before 2021. 

Musk told the jury that he has gone through “three phases” in his beliefs about OpenAI: In phase one, he was “enthusiastically supportive” of the company. In phase two, “I started to lose confidence that they were telling me the truth,” he said. In phase three, “I’m sure they’re looting the nonprofit.” 

Here’s a deeper dive into a timeline of the events as testified in the trial. You can read my dispatches from all three weeks of the trial here and here and here. 

2017: Musk proposes creating a for-profit subsidiary

In 2017, two years after OpenAI was founded, Musk and the other cofounders tried to create a for-profit subsidiary to raise enough capital to build artificial general intelligence—powerful AI that can compete with humans on most cognitive tasks. They fought a bitter power battle over who would get to control the entity. Musk also proposed merging OpenAI with his electric-car company, Tesla. 

During the trial, OpenAI’s lawyers pressed Musk on these discussions, suggesting that Musk knew in 2017 about Altman and Brockman’s plans to pivot the company—even participating in such plans—and had reason to sue then.

“I was not opposed to there being a small for-profit that provides funding to the nonprofit,” Musk told the jury, “as long as the tail didn’t wag the dog.” 

2019: OpenAI creates a for-profit subsidiary with capped profits

In 2019, OpenAI created a for-profit subsidiary, under which employees and investors would receive a capped return on their investment. At the same time, the company secured a $1 billion investment from Microsoft. OpenAI argued that Musk again had reason to sue the company then. 

But Musk testified that he didn’t think the move was violating the nonprofit’s mission. “If you’ve got a capped-profit situation, it hasn’t violated the nonprofit’s goal,” Musk told the jury earlier in the trial. “There was no basis for me to file a lawsuit at that time.”

2020: Microsoft snags an exclusive license 

In 2020, when Microsoft secured an exclusive license to OpenAI’s GPT-3 model, Musk posted on X: “This does seem like the opposite of open. OpenAI is essentially captured by Microsoft.” OpenAI once again argued that Musk had reason to sue then. 

But Musk testified that after reading the post, Altman reassured him that “OpenAI was staying on the mission as a nonprofit.” Musk said although he was skeptical, he still had no reason to sue the company at that point.

2022: Microsoft prepares to invest $10 billion in OpenAI

It was only in 2022, Musk testified, that he discovered OpenAI had abandoned its nonprofit mission. At that time, Microsoft was preparing to invest $10 billion in OpenAI—a deal that closed in 2023. 

“I was disturbed to see OpenAI with a $20B valuation,” Musk texted Altman after reading the news. “This is a bait and switch.”

Musk told the jury this was the moment that made him realize “the for-profit is the tail wagging the dog.” He thought Microsoft would give $10 billion only if it expected “a very big financial return.” He argued that this was the point he realized “OpenAI had become, for all intents and purposes, a for-profit company with a $20 billion valuation.” 

“The 2023 deal was different,” Steven Molo, one of Musk’s lawyers, hammered home during his closing argument.

The jury sides with OpenAI

It was up to the jury to decide whether the evidence supported Musk’s claim that he first realized in 2023 that OpenAI was no longer a nonprofit committed to its mission. In the verdict announced today, they found Musk did in fact have reason to think that he was being misled by Altman and Brockman before 2021. They did not address whether he was in fact misled. 

Courts often decide cases on procedural grounds like statutes of limitations when they can, because it can be the cleaner way to resolve a case than to grapple with its merits.

Musk has said he will appeal the decision to the Ninth Circuit Court of Appeals, a federal appellate court that reviews decisions from district courts in California and other states.

Codon Optimization Isn’t Equal: Benchmarking Gene Design for Antibody Expression



Image of Justin Byers

Justin Byers

Founder and CEO
Axio BioPharma

Panelist

Image of Justin Byers

Justin Byers

Justin Byers is the founder and CEO of Axio BioPharma. He holds a BS in biochemistry and molecular biology from Illinois State University and has held leadership roles at Illumina, Danaher, and Fujifilm. Throughout his career, Byers has led commercial, operational, and cross-functional initiatives supporting biologics programs from early development through manufacturing. He has worked closely with scientific teams to scale workflows, improve process rigor, and align technical execution with strategic objectives. At Axio, Byers oversees corporate strategy, partnerships, and scientific direction. His focus is positioning the company at the intersection of structured data and biologics workflow execution. Axio is accelerating biologics development through mAb production services for R&D while partnering with innovators and CDMOs to ensure the data required for rigorous decision making and a digitally enabled future is generated, structured, and accessible.



Image of Daniel Lin-Arlow, PhD

Daniel Lin-Arlow, PhD

Chief Scientific Officer and Co-founder
Ansa Biotechnologies

Panelist

Image of Daniel Lin-Arlow, PhD

Daniel Lin-Arlow, PhD

Daniel Lin-Arlow, PhD, is a scientist-entrepreneur with deep expertise in synthetic biology and biophysics. Motivated by firsthand challenges in obtaining DNA constructs for metabolic engineering in graduate school, he is deeply committed to providing scientists with the DNA constructs they need for their research. As Ansa’s founding CEO, Lin-Arlow grew the company from two employees in 2018 to more than 70 by 2024, raising over $130 million in venture capital and grant funding to support technology development and commercialization. He transitioned to the role of chief scientific officer in 2024, where he leads the development of new applications of the company’s technologies. Lin-Arlow received his PhD from the University of California, Berkeley for his work in Jay Keasling’s lab for developing the DNA synthesis technology commercialized by Ansa. Prior to graduate school, he was a scientific associate at D.E. Shaw Research where he studied the biophysical properties of G protein-coupled receptors, including how drugs bind and modulate their activity. Dan began his scientific career at MIT, where he earned dual SB degrees in math with computer science and biology, and developed computation tools for the analysis of regulation of gene expression at the Broad Institute of MIT and Harvard. Lin-Arlow is a co-inventor of nine patent families and has co-authored scientific publications in Nature, Science, Cell, PNAS, and Nature Biotechnology.



Broadcast Date: 

  • Time: 

Antibody expression titers are key drivers of screening efficiency in discovery, developability, manufacturing economics, and development timelines. Although it is possible to address poor antibody expression by increasing overall batch size and optimizing downstream processes, the root cause often lies in the underlying DNA sequences. Controlled benchmarking studies are helpful for systematically evaluating DNA construct design decisions that impact titers.

In this GEN webinar, Justin Byers and Daniel Lin-Arlow, PhD, examine how enzymatic DNA synthesis and DNA construct design mitigate antibody expression challenges.

Byers will walk through a controlled benchmarking study of codon-optimization approaches, including details of the study design and how structured, gene-to-protein workflows can help identify optimal constructs before they become downstream problems. He will show that under matched CHO and HEK293 conditions, antibody constructs codon-optimized with an AI codon language model had consistently higher transient expression titers than other approaches. The AI codon-optimized sequences contained “complex” features such as repeats and GC skew that challenge traditional gene synthesis processes but were readily manufactured by Ansa’s DNA synthesis platform. These results suggest that complex sequence features can be important for optimal gene expression, which makes the ability to manufacture them as relevant as the codon strategy.

Lin-Arlow will present Ansa’s enzymatic DNA synthesis technology and the benefits to clients working on antibody production, cell and gene therapies, and other synthetic biology applications. Key takeaways include:

  • An AI-powered codon optimization strategy that measurably improves transient antibody expression yield
  • Why controlled side-by-side benchmarking under standardized conditions is the only reliable way to objectively evaluate DNA construct design choices
  • How integrating rigorous sequence evaluation upstream compresses timelines and reduces the risks of expression failures late in development
  • How Ansa’s fully enzymatic DNA synthesis addresses complex sequences, including: High or low GC content, secondary structures, inverted terminal repeats (ITRs), and homopolymers
  • The Ansa On-Time Guarantee—DNA orders shipped on time, or the complete order is free

A live Q&A session will follow the presentation offering you a chance to pose questions to our expert panelists.

Produced with support from:

ANSA Biotechnology logo

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