The three of them turned off the equipnt, left the laboratory, and the corridor was silent.
As they reached the stairway, Griffin suddenly stopped and said, "Dr. Zhang, thank you."
"Thank for what?"
"You reminded us that research structures shouldn’t just be about shape; we need to consider how they work. That observation about the charge distribution may save us several weeks."
Zhang Lin was a bit embarrassed: "I was just guessing... But as the professor often says, scientific research requires both rigorous data and bold imagination, and both are indispensable. I only have a little unreliable imagination."
"Professor Yang is right," Griffin nodded seriously.
The three headed towards the duty room. The laboratory has many duty rooms for everyone to take a noon nap and stay overnight temporarily.
The next morning, Yang Ping was in his office reviewing Lu Xiaolu’s submitted preliminary structural analysis report when Griffin knocked and entered.
"Professor Yang, my colleague Catherine Miller is eager to visit you in China. She is very interested in K Therapy and hopes to promote it in North Arica. She requests a chance to et you," Griffin asked. The female professor is a leading tumor expert at the Anderson Cancer Center.
Yang Ping pondered slightly, "Let her co."
A few days later, Yang Ping t Catherine Miller in the eting room. She was around forty years old, with blonde hair tied in a neat ponytail, dressed simply in a shirt and trousers, but her sharp eyes exuded the unique temperant of a seasoned researcher.
"Dr. Miller, welco," Yang Ping shook hands with her, "I am Yang Ping."
"Professor Yang, I’m sorry to take up your precious ti," Catherine spoke fluent Chinese, "I read your team’s paper on the chanism of K Factor, which was very inspiring, and I wanted to ask you so questions in person."
"Please sit," Yang Ping gestured for her to sit down, "Is it about the application of K Therapy?"
"More than that," Catherine took out a tablet from her docunt bag and opened a file, "We admitted a group of special pancreatic cancer patients at the Anderson Cancer Center, seven in total. They are all young won with no family history or typical risk factors, yet the tumors progress rapidly and are resistant to all existing therapies."
She swiped the screen to show pathological images and genomic data: "We perford whole-exo sequencing, transcriptomics, proteomics, and even single-cell sequencing, and found a common feature in these tumors -- they highly express a rare fusion protein we nad PAC-FUS1."
Yang Ping carefully examined the data. PAC-FUS1 is an abnormal fusion of two originally unrelated genes, one encoding a cell adhesion molecule, and the other encoding an epigenetic modification enzy. This fusion results in an abnormal protein with both adhesion and chromatin remodeling functions.
"Interestingly," Catherine continued, "in vitro experints showed that PAC-FUS1 can directly bind and activate multiple growth factor receptors, including EGFR and c-T, forming an autocrine growth-promoting loop, which explains the rapid tumor progression."
"But what issues have you encountered?" Yang Ping asked.
Catherine said, "We tried inhibitors targeting these receptors, but the effect was short-lived, and the tumors quickly developed bypass activation. More strangely, when we attempted to treat these patients’ tumors with your published K Factor, we found that it was completely ineffective."
Yang Ping frowned, "Completely ineffective? Are you sure the experintal conditions were correct?"
"Repeated three tis, under strict control," Catherine affird, "Other pancreatic cancers responded as expected to K Factor, but these seven samples showed no change. It’s as if their cancer cells lack the target that the K Factor recognizes."
The statent struck like a lightning bolt through Yang Ping’s mind.
If the PAC-FUS1 fusion protein altered the cancer cell’s identity recognition chanism, hiding or changing that common target, then these tumors would naturally resist K Therapy.
At the sa ti, this also ans that PAC-FUS1 itself could beco a new, more specific target.
"Have you tried targeting the fusion protein itself?" Yang Ping asked.
"We tried RNA interference and small molecule inhibitors, but the effects were limited," Catherine said, "The fusion protein is located between the cell nucleus and mbrane, making it difficult to target, and it may have multiple functions within the cell, making simple inhibition trigger complex compensatory responses."
The eting room fell into a brief silence.
"Dr. Miller, you’ve co at just the right ti," Yang Ping stood up, "Our team is currently researching a common target for pancreatic cancer, which might be the one missing in these fusion protein tumors. You can take a look at our experints."
Catherine’s eyes lit up, "This is precisely the purpose of my visit."
In the laboratory, Yang Ping introduced the team’s current progress to Catherine. When she saw the 3D model of the PANC-ID1 complex constructed by Lu Xiaolu, her expression changed from curiosity to shock.
"You’ve already reached this stage?" she was incredulous, "It took us two years to purify enough PAC-FUS1 for preliminary crystallography with a resolution of just 3.8 Å, and you can already see the structural dynamics in situ using cryo-electron tomography?"
"That’s Dr. Lu Xiaolu’s specialty. Dr. Griffin provided good advice," Yang Ping explained.
Lu Xiaolu briefly explained the technical details to Catherine, who took notes while listening and occasionally raised professional questions.
"I have an idea," Catherine said after listening to the introduction, "If PAC-FUS1 tumors lack the normal PANC-ID1 complex, or if this complex has been modified by the fusion protein resulting in altered function, then it makes sense that K Factor targeting the normal complex is ineffective. Conversely, PAC-FUS1 might exhibit a new identity feature, and if we can design a K Factor to recognize this feature, we could specifically target these highly malignant tumors."
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