Listening and talking

Group photo The last student in my cohort of five has left, and two more are preparing to follow. The group is shrinking, just in time for my promotion to full professor. I’ve enjoyed having Ryanne, Thomas, Laurel, Sneha, and Shailendra in the lab, and it’s been deeply rewarding to watch them grow into capable scientists. Student celebration Mentoring students during, perhaps, the final formative stage of their independent lives has given me a unique perspective. Before they move on—starting families, building careers, still a bit naïve to the skullduggery of middle age—there’s a real sense of possibility. Children photo Our twenties are a strange time: striving for independence in a world that still sees us as kids, yet is quick to deny the grace and security offered to them. It’s a period when many confront—and either overcome, or come to uneasy terms with—the insecurities rooted in childhood. Watching students navigate this stage has been both humbling and gratifying. It lets me relive that age again and again, reflect on how I might have handled it differently, and realize what my own mentors got wrong—or, more often, right.

Memory photo These are the memories I always hoped to make, and it’s been the privilege of a lifetime to experience them while growing alongside my students. I began as an assistant professor eager to make my mark. It doesn’t feel long ago that I was touring what would be my lab space with Gabe and the late John Ferraris (the featured image above). Now, as a full professor, I’m more focused on keeping the funding steady and committee work at bay. Over time, I’ve come to value privacy over recognition. With my social media presence dwindling, I almost look forward to being a bit forgotten.

In my own twenties, I never would have imagined any of this. Back then, I wrote an intensely popular blog—thechemblog—drawing thousands each day to read the angst-ridden, emotional vomit I felt compelled to share. Then came Twitter—a platform full of troublemakers and problems, dressed up as a place for collaboration and solutions. Looking back, I realize no one really needed to hear what I had to say. I just needed to say it. I was fortunate to have advisors, mentors, and friends who were willing to listen. Though some are gone, what they taught is still with me…

Now, though, I’ve found something far more rewarding in listening than in speaking—hearing what these students need to express, what they believe the world should know. Listening as others once did for me, trying to guide without judgment.

Life on the other side of the desk has been both rewarding and painful. But seeing so many students leave—hooded, smiling, prideful—if it has meant anything, it’s been fulfilling to watch myself evolve and grow alongside them. I still feel as though I’m being mentored, though now it is by my own mentees—a younger generation with so much to say, and far too few people willing to truly listen.

MOF-Jets—Even More DIY Drug Delivery

The Group has continued its efforts to “democratize” drug delivery. We had previously published a method on 3D printing micro-needle delivery systems, which graced the cover of PC Magazine and was covered by the popular media.

A homemade MOF Jet in Yalini Wijesundara‘s embrace

Well, we got bored with microneedles and went full Texas and built a gun to just shoot drugs right into people. Yes, Jet-injectors are/were a thing, but they have well-documented issues related to using water as the carrier vehicle. Vaccines and medicines dissolved in water used to be shot into people’s skin; however, the water would splash back out of the injection site and onto the jet injector, spreading disease. Having found a way to powderize and indefinitely stabilize anything—from viruses to DNA adjuvants, to whole cell bacteria, to full liposomes— inside a metal-organic framework called ZIF-8, we figured we could just shoot our drugs as a powder using high-pressure gas and… not only does it work, you can control the pharmacokinetics of the material by using carbon dioxide as the carrier gas.

Yalini and coworkers published the first article in Chemical Science that specifically looks at using carbon dioxide to dissolve the ZIF quickly once it gets into tissue. As we all know, carbon dioxide in water becomes carbonic acid, and acids very rapidly dissolve the ZIF shell. Consequently, when one shoots a ZIF-coated material into tissue using carbon dioxide, the material is delivered into the skin and is bioavailable almost immediately. If one uses air, which does not react with water and does not form any acids, the material enters the skin still in the ZIF coating. That coating takes a few days to dissolve, slowly becoming bioavailable over several days. This has become pretty popular with no shortage of write-ups in the popular media. This is all explained pretty well in a press release by the American Chemical Society (ACS). Yalini gave a talk at the ACS National Meeting in Indianapolis, and by chance, the ACS picked her abstract for a press release. They even made a video that explains it (below):

Comparative studies between pristine and ZIF-8-coated liposomes demonstrate the mechanical stability of the ZIF-8 coating. Pristine liposomes leak under the shear stress of the MOF-Jet, while ZIF-8-coated liposomes remain protected, and negligible leaking is observed. The hard coating of the ZIF-8 allows the coated liposomes to penetrate into the tissue model while the pristine liposomes just pool on the surface.

We even went a step further and showed how the mechanical stability of the ZIF promoted the shooting of delicate liposomes into tissues. Sneha’s PNAS article shows that the enhanced mechanical strength offered by a shell of only ~100 nanometers thin is sufficient to let liposomes be shot into the skin. Liposomes, like most lipid nanoparticles, are notoriously fragile and do not survive the strong forces of being shot onto a surface. Liposomes can resist forces up between 100pN to 1nN, which is very small; however, inside a ZIF Shell, about 100 nM thick, this increases to ~3 μN, representing an enhancement of many orders of magnitude.

Graduations and Fellows of Royal Societies

Congratulations to two graduated rockstars, Dr Olivia Chastain (née Brohlin) and Dr Arezoo Sharivarkevishahi, who went off to be Senior Scientists at Merck and Pfizer respectively a few months ago. Jeremiah was exceptionally happy to have them return so he could hood them and remind them of how special they were one last time before they went back home with their fancy printed and bound thesis. Also, recently, following the successful deposit of his cheque, Jeremiah was elected Fellow of the Royal Society of Chemistry, which has permitted him to use the post-nominal “FRSC”, which Jeremiah enjoyed for about a month before the novelty wore off. The fancy little diploma the Royal Society of Chemistry sends is shown. It was printed on A4 paper, which was difficult to find a suitable frame for in the land of the free and home of the brave. That said, it was found. Now Jeremiah is off collecting other Fellowships to fatten his CV to match his ever expanding waistline.

Hopefully, a new tradition? The Handing of the Thesis!

Welch Renewed!

The group is very thankful to the Welch Foundation for renewing our grant. This grant (100K direct costs per year) is focused on some of the fundamental discoveries made by group Alumna Arezoo Sharivarkevishahi in photoimmuno therapy using virus like particles. To celebrate, the group went out and played Whirlyball and laser tag where Jeremiah was basically beat the whole group single-handedly.

C&E News Calling!

Arezoo Shahrivarkevishahi’s paper in JACS was recently covered by C&E News! Arezoo even goes on to speculate what the future of the project might bring: “The good thing about viruses is that we can not only decorate their surfaces but also load things inside them,” Shahrivarkevishahi says. Although the current study presents a simple version of the approach, loading Qβ coat proteins or another VLP with chemotherapy or other cancer drugs could further potentiate the treatment’s efficacy.” Congrats, Arezoo and team!

Crunchy on the Outside, Soft on the Inside

A recent collaborative paper with the Meloni lab has hit the news. Fabian Castro, a third-year grad student, did work with help from the Meloni Crew on making room-temperature stable liposomes, proteoliposomes, and protein-detergent micelles. All the formulations were so stable they could be stored at room temperature and even mailed around the US in an envelope for weeks at a time. There are pretty big differences between the COVID-19 vaccine and the liposomes we used here, but it’s probably obvious what we are doing next.