A Scientist and a Biker: An Exclusive Interview with Professor Mu Wang, Dean of XJTLU Wisdom Lake Academy of Pharmacy

Aug 28, 2023 08:33 CST Updated 08:33

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Put on your helmet, and you took out the key.

Conduct a comprehensive vehicle inspection, enter the vehicle, shift to neutral, fully depress the clutch with the left hand, ignite the engine, activate the left turn signal, check the rearview mirrors, perform a head check, simultaneously twist the throttle with the right hand while slowly releasing the clutch with the left hand, and start off smoothly.

This is a compliant motorcycle starting mode.

The engine RPM continuously hits the shift point, triggering upshifts as the motorcycle steadily accelerates. Your focal point extends with the perspective of the road ahead, yet you remain acutely aware of every factor outside that focus that could affect your riding. A bump on the ground 200 meters away might be a stone; you subtly shift your center of gravity, guiding the motorcycle along a new line to skim past the obstacle.

Entering the corner, you quickly downshift to achieve the ideal entry speed, push the handlebars, lean your body significantly, gently apply throttle to maintain a constant speed through the mid-corner, and keep your eyes focused on the exit point.

At this moment, if you apply the front brake, you will lose control and crash; if you engage the clutch, you will lose control and crash; if you lean your body excessively, you will lose control and crash.

This experience, which causes pupil dilation and a rapid spike in heart rate, where even slight deviations from standard operating procedures can lead to catastrophic consequences,For President Wang Mu, it is a state of focused relaxation.

1Standardized Adventurer

As the inaugural Executive Dean of the School of Pharmacy at Xi’an Jiaotong-Liverpool University, Professor Mu Wang exudes an aura that defies the stereotypical image of a scientific researcher.

This may stem from his years of riding experience. Professor Wang Mu began his studies in the United States in 1988. In addition to nearly three decades of studying, conducting research, and teaching in the U.S., he honed his riding skills by taking advantage of the country’s superior road infrastructure. He started on a Kawasaki 125, gradually upgraded to a 250cc model, then switched to a Yamaha 600, and ultimately mastered liter-class heavy motorcycles.

An American motorcycle instructor told him that among motor vehicle operations, riding a motorcycle is the most difficult, followed by flying an airplane, while driving a car is the easiest. Professor Wang Mu never uses his motorcycle for commuting; instead, he rides it to relieve stress. He favors two riding styles in particular: one is leaning into turns while circling within urban roundabouts (any experienced motorcyclist knows that low-speed, tight-circle maneuvering is a highly challenging technique that demands considerable skill); the other is speeding over a short stretch on highways for an adrenaline rush (if caught by the police, he simply accepts his bad luck).

An individual capable of riding a motorcycle at speeds exceeding 160 km/h possesses a risk assessment framework that differs from that of the average person.

On Professor Wang’s driver’s license, in addition to the “Motorcycle Endorsed” designation (in the United States, a motorcycle endorsement is indicated by printing these words on the standard driver’s license), you can also see the notation “Donor+Heart,” signifying that he is a full organ donor.

Bungee jumping—particularly the variant that uses an elongated cord to allow free fall closer to the water surface—as well as skydiving, are also part of Professor Wang’s post-retirement plans. He was quite inspired by anecdotes about former U.S. President George H.W. Bush’s long-term skydiving activities. The “biggest regret” in Professor Wang’s life thus far is his failure to persist in obtaining his pilot license.

However, none of this implies that Professor Wang Mu is one who takes blind risks. As mentioned in the introduction, Professor Wang Mu, like all qualified motorcyclists, adheres to the most stringent Standard Operating Procedures (SOPs) for riding, eliminating all uncontrollable factors and keeping controllable risks firmly under his own control. Indeed, those who frequently engage in high-risk operations tend to impose even stricter requirements on preparatory work and maintain tighter control over risks.

Just like the mount Professor Wang Mu chose for his WeChat profile picture: the Yamaha XJ6, a stable, reliable, and time-tested 600cc high-displacement motorcycle.

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2Anticipatory Lead Time

On August 15, Professor Wang Mu and his team published an article titled “Targeting SOD1 via RNAi with PEGylated graphene oxide nanoparticles in platinum-resistant ovarian cancer” in the Nature subsidiary journal Cancer Gene Therapy.

In this study, building on their prior original finding that cisplatin chemoresistance in ovarian cancer is positively correlated with superoxide dismutase 1 (SOD1) overexpression, Wang Mu’s team conducted a series of in vitro cellular studies and demonstrated that reducing SOD1 expression in cisplatin-resistant cell lines can effectively reverse cisplatin resistance.

Based on this resistance-associated physiological characteristic, the team constructed and screened various graphene nanomaterials as nucleic acid delivery vectors to deliver small interfering RNA (siRNA) targeting specific proteins into drug-resistant cells via these graphene carriers. This approach effectively reduced SOD1 protein expression in drug-resistant cells, thereby sensitizing them and reversing their drug resistance. In preclinical studies using relevant mouse models, the combination of this nano-siRNA therapeutic with cisplatin effectively inhibited the growth and metastasis of cisplatin-resistant tumors, while demonstrating favorable biosafety and low toxicity.

Professor Wang Mu’s ultimate goal is to improve the five-year survival rate of patients with platinum-resistant recurrent ovarian cancer by combining cisplatin chemosensitizers (nano-siRNA) with cisplatin chemotherapy.However, Professor Wang Mu’s pursuit of the clinical application of siRNA was by no means a whim.

Just as one anticipates road conditions hundreds of meters ahead, Professor Wang Mu was already forecasting the future “road conditions” for small nucleic acid drugs well in advance, prior to his return to China in 2018.

Unlike the current landscape, where more than a dozen small nucleic acid drugs—including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and aptamers—have flooded the market, the future of this technological pathway was uncertain before the FDA’s approval of the world’s first siRNA drug, patisiran (indicated for the treatment of polyneuropathy caused by hereditary transthyretin-mediated amyloidosis).

Professor Wang Mu has accumulated over a decade of basic research experience in the mechanisms of drug resistance in ovarian cancer. Although small-molecule inhibitors targeting SOD1 have not yielded satisfactory results, downregulating SOD1 expression via siRNA still holds promise. What Professor Wang needs to do is to prepare for fine-tuning based on the overarching strategy, much like a motorcyclist who remains ready to adjust their center of gravity at any moment.

Drawing on his own sources within the FDA and the clinical progress of Patisiran, Professor Wang Mu received positive feedback from the FDA regarding the druggability of siRNA therapeutics. This signal guided the trajectory of Professor Wang Mu and his team over the next five years.

3Launch is for conversion

Professor Wang Mu has not merely paid lip service to the translation of scientific research achievements into clinical applications.

Early in his career, Professor Wang Mu participated in a prototypical “industry-academia-research-government” collaboration. At that time, the Indiana state government, Indiana University School of Medicine, and Eli Lilly and Company jointly established a contract research organization (CRO) with protein analysis as its core platform. After more than five years of development, the company provided academic researchers, including Professor Wang, as well as local startups, with access to state-of-the-art protein analysis platforms, thereby facilitating his emergence as an expert in biomolecular mass spectrometry and proteomics.

This experience marked the starting point for Professor Wang’s future collaborative projects with numerous major pharmaceutical companies and biotech firms.

As a researcher dedicated to elucidating the fundamental mechanisms underlying innovative drugs, Professor Wang Mu has accumulated extensive experience in collaborative development with industry partners in the U.S. market, which demonstrates greater openness to interdisciplinary and cross-sector collaboration. This has enabled him to gain a comprehensive understanding of corporate R&D needs and quality monitoring standards, including QA and QC processes and FDR control. In Professor Wang’s words, “I have a heightened sensitivity to the importance of validation compared to typical basic science researchers.”

Taking the early collaboration with Genentech as an example, while assisting in protein analysis to identify biomarkers, Professor Wang Mu adhered to the highest standards by rigorously verifying potential off-target effects at every step. This process not only accumulated cutting-edge industry know-how but, more importantly, established a heightened emphasis on drug development, particularly during Phase I clinical trials. Much like operating heavy machinery, the preliminary work is paramount and cannot be overlooked.

The research findings were also planned with the ultimate goal of “treating diseases and saving lives.” In Professor Wang Mu’s next steps, in addition to follow-up studies, he also hopes to collaborate with pharmaceutical companies that share this common goal to advance Phase I clinical trials.

4Conclusion

During the interview, Professor Wang Mu repeatedly emphasized the importance of preliminary work. Whether it was the pre-ride inspection before riding a motorcycle, the calibration training for learning to fly an aircraft, or the proof-of-concept stage for research findings, his adventurous spirit and meticulous preparation might appear contradictory to laypeople. However, those with similar experiences can understand the certainty this approach brings—advancing in an orderly manner through dynamic balance, rather than relying on mere stability.