On July 14, graduate student Natasha Sheybani successfully defended her dissertation to earn a PhD from the Department of Biomedical Engineering in the University of Virginia (UVA) School of Engineering & Applied Science. “Leveraging Focused Ultrasound to Potentiate Immunotherapy for Primary and Disseminated Solid Tumors” was the accumulation of five years spent studying the use of focused ultrasound for cancer immunotherapy.

Sheybani2The Foundation has supported Dr. Sheybani's work in the past, and in September, she plans to present a Foundation webinar on using focused ultrasound for enhancing gene therapy. Read on to learn more about her educational journey and future plans.

You started college when you were only 16 years old?
Yes, I graduated from the Appomattox Regional Governor’s School for Arts & Technology and then started college at Virginia Commonwealth University (VCU) when I was 16. I was part of the Honors program there and finished my bachelor’s degree in Biomedical Engineering in three years. I started my PhD studies at UVA immediately thereafter.

How did you choose UVA for your graduate program?
Throughout high school and college, some really fantastic research experiences in neurobiology and drug delivery fortified my interest in pursuing a PhD in biomedical engineering (BME). It was my research advisor, Dr. Hu Yang (whose lab I had worked in since I was 14), who first keyed me into the BME program at UVA after I expressed interest in pursuing image-guided drug delivery. When I eventually visited for a recruitment weekend, I was highly impressed with the vibrant culture of collegiality and collaboration in the department. Having the option to engage in translational research was also important to me. Thus, UVA BME’s unique co-location within the School of Medicine and Health System immediately caught my attention. I have found that this arrangement organically facilitates opportunities for collaboration, clinical translation, and observable impact. Most importantly, UVA is a globally pioneering institution for focused ultrasound technology and a Focused Ultrasound Center of Excellence.

When and how did you get interested in focused ultrasound?
It turns out that I had interest in focused ultrasound even before I even knew what it was. When I applied to graduate programs, I placed emphasis on programs with a research footprint in image-guided drug delivery. Given the drug delivery/biomaterials “roots” that I established via undergraduate research, making a lateral move into the realm of image-guided therapy seemed like a natural choice. In retrospect, it is uncanny that this criterion actually brought onto my radar screen many labs that were doing focused ultrasound research. I became fully captivated by the technology when I eventually interviewed with Dr. Richard Price, my PhD advisor. After that interview and some additional reading on the topic, I had no doubt that I wanted to contribute to the field. I direct-matched with the Price Lab, and this was the best decision I’ve ever made.

What are your areas of interest in focused ultrasound? What mechanisms and clinical indications do you study?
My PhD work has been centered on using focused ultrasound for immunomodulation, extracellular vesicle modulation, and drug delivery. To this end, the mechanisms I have worked most with are blood/brain tumor barrier disruption, thermal ablation, and hyperthermia. I have gained broader exposure through collaborations with the Foundation’s Merkin scholars. With Dr. Frederic Padilla and Dr. Cyril Lafon, I have explored the immunological impact of a wider array of thermal and mechanical focused ultrasound regimes in triple negative breast cancer. With Dr. Francesco Prada, I have explored sonodynamic therapy with fluorescein in glioblastoma. Down the road, I am keen on exploring other mechanisms of focused ultrasound as they relate to immunotherapy as well as its use for amplification of cancer biomarkers in the context of liquid biopsy.

What was the goal of your PhD work?
The goals of my dissertation were to understand the mechanisms of innate and adaptive immune responses elicited by focused ultrasound to primary or disseminated tumors and then use this information to design and test immunotherapeutic approaches predicted to synergize with focused ultrasound. I worked in murine models of glioblastoma and triple negative breast cancer to fulfill these objectives.

What advice would you give someone who is thinking about pursuing a PhD?
Don’t be afraid to advocate for yourself and find caring mentors who are willing to do the same. Before applying to graduate school, try to cultivate meaningful research experiences, seek advice from students who have followed the same path, and build your network early! Reach out to programs or labs that pique your interest. It is never too early to start those conversations, and you would be surprised at how receptive professors can be to an email from a curious, ambitious student. These steps will equip you with the information you need to weigh against your interests and priorities and ultimately make the choice that is best for YOU.

P.S. – for those who have just started graduate school, I will share some additional thoughts (albeit unsolicited). These nuggets of wisdom draw from Peter Diamandis’ Creed for the Passionate and Persistent Mind (i.e. “Peter’s Laws”). I held on to these reminders during grad school, and I hope they benefit other students:

  • Do it by the book…but be the author!
  • Patience is a virtue, but persistence to the point of success is a blessing.
  • Fail early, fail often!
  • Multiple projects lead to multiple successes.
  • If it were easy it would have been done already.
  • The best way to predict the future is to create it yourself!

Were there times you thought about changing your path?
I don’t think I ever questioned the concept of pursuing higher education. I think it was always in the cards because I grew up in a family that deeply values education. The interesting thing about my path was that in college, I also became majorly invested in some global health work with prison children that almost took me down the path of pursuing a PhD in public health. Although it was a tough decision, my investment in biomedicine and engineering was already too strong to shift course from a PhD in BME.

How did your parents support your academic journey?
My mom and dad are both university professors and thus fostered my love of learning in so many ways growing up. Needless to say, they have always been such remarkable models for the rewards and demands of an academic career - so much so that my younger brother is now pursuing a PhD in engineering as well.

My parents have supported my academic journey in countless ways. When I started research at VCU (before I could legally drive), they would embark on hours-long round trips regularly to deliver me to and from the lab. When I have been faced with critical decisions about my education, they have been a tireless sounding board, not to mention my number one advocates when situations called for it. Whenever I was confronted with frustrations or challenges during graduate school, I was able to turn to them as voices of reassurance and reason. It was in those moments that they taught me the lessons that no amount of education can teach: be confident, be good to yourself, live a life of purpose, treat everyone with kindness and respect, and surround yourself with people who lift you higher. Lastly and most importantly, I deeply appreciate the fact that my parents have always prioritized my and my brother’s happiness above all else. By their own example, they have taught us to stay happy, positive, empathetic, and grateful – no matter how difficult the circumstance. I’m sure what makes them most proud is knowing that we embrace these values in life and even in our academic pursuits.

What comes next?
This September, I will begin a postdoctoral fellowship at Stanford University. I will be co-mentored by Daniel Rubin, MD, MS (Professor of Biomedical Data Science, Radiology, and Medicine and Director of Biomedical Informatics for the Stanford Cancer Institute) and Ash Alizadeh, MD, PhD (Associate Professor of Medicine in Oncology). I will be supported by an NCI F99/K00 Predoctoral to Postdoctoral Transition Award.

What will you be doing for your postdoctoral project?
While I will be maintaining a footprint in focused ultrasound through collaborations, my main postdoc project will allow me to cultivate additional expertise in biomedical imaging informatics, functional genomics, and computational biology. I will be integrating features from circulating tumor DNA and PET/CT imaging into a machine learning-based radiogenomics framework. The goal will be to leverage this framework and adaptations of it to noninvasively model clinical risk and personalize treatment for cancer patients undergoing conventional chemotherapy or novel therapies like CAR T-cell immunotherapy. I hope to someday usher these emerging approaches for individualized clinical decision making into the field of focused ultrasound immunotherapy.

Has the Foundation played a role in your work?
Absolutely - the Foundation has played a profound role in my personal and professional journey. Some of my projects during graduate school were funded by Foundation grants to Dr. Price, and I benefitted greatly from the Foundation’s incomparable educational resources over the years. Additionally, I enjoyed engaging in productive collaborations with world-renowned Merkin Scholars, rich scientific dialogues with colleagues and mentors at Focused Ultrasound Foundation symposia and workshops, opportunities to mentor Global Interns, and so much more. The positive interactions I had with the Foundation and broader focused ultrasound community played such a transformative role in my work over these past five years – and this is a major reason that my dedication to this field is unwavering. I am immeasurably grateful to Dr. Neal Kassell for his mentorship, generosity, kindness, and wisdom – as well as to all of the inspiring members of Foundation team for making the focused ultrasound community feel like home.

Past Coverage
2019 Summer Intern Report: Jackie Brenner August 2019
UVA Student Researcher Earns Prestigious Award from the National Cancer Institute October 2018

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