Maya Holay

PhD Graduate Student, 5th Year

Adventures in Nanomedicine

Interviewer: Wei Ji Chen

Maya Holay attended Carnegie Mellon University, graduating with a bachelor’s degree in Chemical and Biomedical engineering in 2017. She began her graduate studies in UC San Diego’s Nanoengineering department and is currently a fourth year PhD candidate working in Bioengineering affiliate faculty Dr. Liangfang Zhang’s lab. Her current research aims to expand the biomimetic therapeutic toolbox by developing novel cell and extracellular membrane coated nanoparticles.

What is your research focus, and why did you choose it?

My work is focused on exploring novel cell and extracellular membrane materials to expand the biomimetic toolbox for targeted drug delivery and mucosal vaccination applications. I believe Dr. Liangfang Zhang’s work in cell membrane coated nanoparticles is an ideal platform to combine my skills in chemical and biomedical engineering. Chemical engineering follows a classic engineering school of thought, multi-step planning, solving problems in discrete phases, and real world applications. Biomedical engineering is simply the application of such principles to medical use. My work in cell membrane nanoparticles bridges the systematics I was taught in chemical engineering with the innovation needed to translate my drug delivery research to address medical needs.

Can you elaborate more on cell membrane coated nanoparticles?

Because of the increasing threshold in what is considered safe and effective drug delivery, nanoparticle development offers a new standard in precision medicine by targeting sites in the body to minimize side effects or harm to patients. By cloaking nanoparticles with a cell membrane, nanoparticles are able to evade the immune system and stay in the body for an extended period of time to deliver the therapeutic payload. Because of the endless combinations in cell membranes and nanoparticle payloads, the possibilities of nanoparticle functions are endless. Genetic modifications can even be made to a cell line in order for it to express particular or necessary receptors before the membranes are extracted and utilized.

What are the challenges and advantages of nanomedicine compared to the standard pharmaceuticals?

The nanomedicine fabrication process is very different from the current drug development pipeline in the pharmaceutical industry, since we are working at the nanoscale. The characterization and formulation of nanoparticles require different procedures, protocols, and equipment. We often struggle with polydispersity, which means nanoparticles are not always the same size. Another challenge is the lack of comprehensive understanding of how nanoparticles react once in the body, leaving us apprehensive to administer novel formulations to humans prior to more in-depth study.

Nanoparticles have a significant advantage over the small molecule based drugs in pharmaceutics, because they are formulated to be delivered with greater precision with less side effects. A current clinical example is Doxil. Doxil is a nanoengineered chemotherapeutic drug composed of nanoscale liposomes capable of targeting tumor tissues via the EPR Effect (Enhanced Permeability and Retention) and penetrates deeper into tumor tissue compared to macromolecule drug delivery.

Recently, Jennifer Doudna and Emmanuelle Charpentier have won the Nobel Prize in Chemistry due to their work in CRISPR. Do you believe CRISPR’s recognition on the highest level affects the field of bioengineering and if so, how do you think it will?

Indeed it’s exciting to see CRISPR being acknowledged on this level. Increasing open access to science means that we, as an academic community, can further technology before it brings the attention of something as monumental as the Nobel Prize. I believe one of CRISPR’s greatest impacts in the bioengineering field is by providing researchers with tool building technology. There are many rare diseases that are without a model, there’s no accurate way to test out potential therapeutics before it is pushed to human trials. CRISPR provides a particular method to modify our systems to model rare genetic diseases through cell culture and animal models.

What does it mean for women involvement in STEM for these two distinguished scientists to be celebrated on such a stage?

This is the first time that a Nobel prize in STEM has been awarded solely to women - which is a bit mind blowing! It’s 2020 and we feel like we’ve broken down a lot of gender barriers but the fact that this is the first time shows that we’re still experiencing those gender barriers. It’s absolutely exciting because it demonstrates that the Nobel Prize committee is committed to recognizing women who are working hard to discover new scientific concepts and making these concepts accessible to the public. It’s a big win for gender equality in STEM and demonstrates that we can be recognized just like men can.

Who is your faculty advisor? How does he/she help your research?

Being a well-established tenured professor with connections to local nanomedicine companies, Dr. Liangfang Zhang, an affiliate with the Bioengineering Department has offered me many exciting opportunities to engage with industry and various collaborators. He has extensive experience in writing grant proposals, securing funding for the lab, and that has led me to working on cutting-edge projects with a rich pool of resources. Because of our industrial collaborations, I’m invigorated and inspired when I see the translation between academia papers to the industrial pipeline in pre-clinical trials, clinical trials, and ultimately a product that makes a real world impact . Along with Dr. Zhang’s personal expertise, the lab houses many individuals with different experiences and backgrounds so if I have a question, there’s usually someone with the answer. Whether it is about a specific assay or a new technique, there’s always someone who can help me with my inquiry.

What is the work-life balance of a PhD student? What do you do in your free time?

For me, the work-life balance happens when I have scheduled time to invest in my other interests. I’ve swum since I was a kid so being in San Diego gives me a chance to indulge in that venture by swimming with the Masters swim team here at UCSD. I also volunteer with the San Diego House Rabbit Society. Both these extracurriculars have scheduled practices/shifts, so it necessitates me to plan my schedule ahead of time and make time to do things I enjoy. Unlike a 9-5 job, graduate students are not expected to be in or out at a certain time, so many feel they have to constantly work and this can create a stressful cycle of work, eat, sleep, and repeat. I combat this by treating my research like a job - and trying to limit my work hours to time I’ve already set aside . While others may think this is too little time, this limit actually forces me to be more efficient in planning out experiments, eliminating wasted time at the bench, and setting up internal deadlines for minor tasks improved my ability to be in a constant flow of work. Moving between classes, research, and teaching became much more of a smooth transition in my daily schedule instead of a painful juggling act of sleepless nights and headaches.

If you could give one piece of advice to undergraduate students who are pursuing research, what would it be?

Set boundaries and set expectations. Once you’ve found a lab, be sure to establish clearly what you wish to gain from the experience, whether that be familiarizing yourself with the research field, learning techniques, or gaining publications. It’s completely fine to change your initial expectations once you’re more experienced. Setting boundaries, such as desired work hours or days ensures you can work at your best pace and limit burnout. Never be afraid to set boundaries, it demonstrates maturity and an unspoken understanding that you are committed to what you promise.