Big Impact in Bio: Developing Nanomedicine and Mentoring Young Scientists the World-Over
When Bronwyn Scott received a Stamps Scholarship a couple years ago, she cited an Amgen Scholar as the person having the greatest impact on her in her college career: “My incredible research mentor Dr. Joy Wolfram had inspired me to work hard, believe in myself, and remain unapologetic for my passion and drive. She continuously pushes me to reach for goals I thought were unattainable.”
As Scott’s undergraduate research mentor at the Houston Methodist Research Institute in 2013, Wolfram advised her to take a fresh perspective in designing her research project. “Bronwyn came up with the unique idea of using a yeast enzyme for cancer treatment,” Wolfram recalls. “This enzyme converts glucose to a harmful agent that can destroy cancer cells. Amazingly, the project was successful and Bronwyn published a first author and two coauthor manuscripts.”
This type of mentorship is a driving force for Wolfram, who works both to tackle life-threatening diseases at the Mayo Clinic in Florida and to give others, especially underrepresented minorities in science, the tools to do so. Her goal is to bring to the clinic new nanomedicines with increased therapeutic efficacy and safety.
Wolfram, a 2009 alumna participated in the Amgen Scholars Program at the Karolinska Institutet in Sweden, where she studies a novel protein that increases cancer cell migration. After completing a master’s degree in biology from the University of Helsinki in her home country Finland, she got a position in nanomedicine at the Houston Methodist Hospital, which is part of the largest medical center in the world. She also enrolled in a joint Ph.D. program with a Chinese university, and then landed at the Mayo Clinic after getting her Ph.D., where she now leads the Nanomedicine and Extracellular Vesicles Lab. She also holds affiliate faculty positions at the Houston Methodist Hospital in Texas, the University of North Florida, and the Wenzhou Institute of Biomaterials and Engineering in China.
We spoke with Wolfram to learn more about her path to science, her work with nanomedicine, and her experiences in biotech research in China.
ASP: How did you become interested in science?
Wolfram: As an 11-year-old, I accompanied my dog to the veterinarian to treat a skin infection. I watched with fascination as swab cultures of the infection were seeded in bacterial plates to determine a suitable antibiotic treatment. I asked the veterinarian if I could have some culture supplies but she shook her head in disapproval. However, as I was walking out, she secretly passed me a bag of supplies and whispered, “don’t tell anyone.” I excitedly went home and started building a miniature microbiology laboratory. My first experiment was swabbing refrigerator shelves. After a few days, the bacterial plates were full of different colors and various shapes. I summoned my family and announced that our refrigerator was crawling with bacteria! They stared at me in horror. As I witnessed my dog quickly recover from the skin infection, it dawned on me that our refrigerator was not unusually dirty; science was just unusually cool!
ASP: What led you to pursue nanoparticles specifically?
Wolfram: As a child, I witnessed many of my friends’ parents succumb to cancer. I was frustrated that several decades of cancer research had led to only minor improvements in patient outcomes. I wanted to change the way cancer research was performed and decided to work with nanotechnology.
Nanoparticles are like tiny cars that can travel in the blood to specifically deliver medications to diseased tissues, leading to reduced side effects and increased therapeutic efficacy. The reason that conventional medications fail is due to the complexity of diseases, including abnormalities in several signaling pathways and low levels of drug accumulation in diseased tissues. Nanoparticles can overcome these challenges, as they can be loaded with several different drugs that can simultaneously be delivered for greater impact. Moreover, additional features can be added to the nanoparticles, including targeting ligands, permeation enhancers, and coatings that reduce rapid clearance.
ASP: What has been the most exciting finding coming out of your nanoparticles research?
Wolfram: One of the surprising findings we have discovered is that changes in the size and shape of nanoparticles can dramatically improve tumor accumulation and therapeutic efficacy. We have also found that nanoparticle homing to diseased tissues can be increased by temporarily blocking the liver to prevent nanoparticles from getting stuck in this organ. Currently, my team is also developing several promising therapeutic strategies based on biological nanoparticles that we collect from patients.
ASP: What impact are you most proud of from your current work?
Wolfram: One of the major drawbacks of nanodrugs is that they get stuck in the liver, as this filtration organ has immune cells that engulf foreign materials. To solve this problem, we studied whether any known medications could block the activity of these immune cells. We found that the antimalarial drug chloroquine was able to prevent immune cells from trapping nanoparticles in the liver. This strategy is an easily implementable and broadly applicable approach to improve nanoparticle therapy, as chloroquine has already been widely used in patients. I am now collaborating with oncologists and nanomedicine companies to initiate a clinical trial at Mayo Clinic based on this approach.
ASP: What is it like working in China in biotechnology?
Wolfram: Every time I land in Beijing, I am at the center of the world! During my morning walks to the Chinese National Center for Nanoscience and Technology, buildings would appear out of nowhere. The quick changes in scenery mirrored the fast-paced scientific environment. The center is an international hub for innovation in nanotechnology. I met more individuals from the United States Food and Drug Administration and the National Institutes of Health during one semester in China than several years in the United States.
Foreign visitors watched in bewilderment as Chinese students lay fast asleep at their desks in the middle of the day. This observation could have led to snap judgments about work ethic, but a closer look revealed that the resting period was a deliberate strategic effort to recharge in order to work long into the night. In addition to their hard-working nature, the Chinese scientists and professors impressed me with their hospitality. On a weekly basis, I was invited to elaborate dinners with rotating tables that would offer a greater variety of dishes than covered by the entire Finnish cuisine.
Today, in my joint appointment as an associate professor at the Wenzhou Institute of Biomaterials and Engineering in China, I look back in gratitude to the science, friends, and collaborators that arose from my Chinese adventure.
ASP: Can you describe some of the roles you have for mentoring young scientists?
Wolfram: One of my main goals is to inspire students to think differently and have the courage to tackle life-threatening diseases. If we can encourage others to become visionary leaders, the opportunities to improve the world are boundless. My goal is also to be a role model for women in science, and I have been actively involved in educational activities and community outreach. For examples, I am the Co-Chair of National Cancer Institute Physical Sciences-Oncology Network Education and Outreach Working Group. For the past five years, I have also organized outreach events with hands-on activities that expose K-12 grade students to science. During my research career, I have had the pleasure to mentor many outstanding individuals, including, Bronwyn Scott.
ASP: How do you think the Amgen Scholars Program prepared you for your current work?
Wolfram: The Amgen Scholars Program solidified my passion for translational research and made me confident in a laboratory environment. In addition to gaining skills in several experimental techniques, I also learned how to think like a scientist. The conference at the end of the program, which was held at the University of Cambridge in the United Kingdom, introduced me to a broader international community of scientists and gave me a strong sense that scientific problems are solved through a global effort. The Amgen Scholars Program provided me with me the confidence to venture out into the world. After completing the program, I have been extensively involved in international research collaborations between the United States, China, and Europe.
ASP: What advice do you have for Amgen Scholars?
Wolfram: Find a purpose that benefits the greater good and be part of something bigger than yourself. Write down your goals and make them specific and exciting. Be persistent, as this quality seems to be the main determinant of success. Having a positive attitude will make everything easier and more enjoyable. Network like crazy! Life is short, so be unafraid to take the unconventional path.
ASP: What is the driving force behind your work?
Wolfram: Patients provide daily inspiration for our research and serve as a reminder of the importance and urgency of our mission. Our goal is to benefit a large number of future patients with the nanomedicine treatments that we are developing. The development of new therapeutic agents is a laborious process that usually takes at least 15 years and costs $1 billion. Despite the hurdles ahead, we do not give up and keep our end goal in focus.