Katherine W. Ferrara, PhD, is a Distinguished Professor of Biomedical Engineering at UC Davis and the Director of their Center for Content Rich Evaluation of Therapeutic Efficacy. She also serves on the Foundation’s Research Advisory Committee and has contributed as faculty during our biennial Symposium.
In this interview, she addresses questions about her career, her laboratory at UC Davis, and her work.
Q. When and how did you get interested in focused ultrasound?
I grew up in Pennsylvania and initially became a physical therapist. Later, I went back to school and received my PhD in electrical engineering from UC Davis. I then worked in ultrasound engineering for many years, starting in the 1980s with GE medical systems as part of a group called design west. We developed significant components of GE’s first MRI unit. Our group was integrated into their early ultrasound business, and I’ve been interested in various aspects of ultrasound imaging and therapy since that time. When GE moved their ultrasound business from California back to Milwaukee, many of us went on to do different things. I enjoy both industry and academics so I moved to the academic world at UC Davis.
Q. What mechanisms and applications of focused ultrasound do you study?
I would say that 50% to 60% of our research work involves focused ultrasound. Our main areas of interest are:
1. The Physics of microbubbles
My laboratory has done a lot of work on the basic physics of microbubbles, and not necessarily in conjunction with focused ultrasound. Studying these topics led us to believe that there could be therapeutic effects associated with combining them with sound.
2. Image-guided drug delivery
Our overall focus is image-guided drug delivery. We synthesize nanoparticles and sometimes deliver them with focused ultrasound, but not always. We have had several projects where we looked at how ultrasound and microbubbles work together for drug delivery. We’ve also developed methods for tagging these particles with a radiotracer to determine how much drug is delivered with and without ultrasound (molecular targeting). We are interested in delivering drugs, nucleic acids, and carriers. We are also developing new transducer arrays geared toward integration in image-guided delivery.
Recently we began integrating immunotherapy into our protocols. The challenge is to optimize the multiple and complicated aspects of the protocols - there are many parameters to control. For example, our studies with focused ultrasound and immunotherapy have tested 10 to 15 different combinations of two immunotherapy drugs with focused ultrasound, in combination or alone.
Q. Describe the mission, size, and scope of your laboratory?
The Ferrara Lab is a part of the department of biomedical engineering on the campus of the University of California Davis. Our projects span all aspects of image-guided drug delivery, including the fusion of images between ultrasound, PET, MRI, and CT, the development of activatable drug delivery vehicles, and the development of molecularly targeted drug delivery vehicles. Members of our laboratory bring expertise in biomedical engineering, physics, electrical engineering, chemical engineering, mechanical engineering, computer science, materials science, chemistry, and biology.
For focused ultrasound, we have two MR-guided focused ultrasound systems from Image-Guided Therapy – one is used to treat small animals and the second is installed at our veterinary hospital. The latter has a larger bore system with a 256-element array integrated into a clinical magnet. We have a goal to treat veterinary patients similar to efforts in the National Cancer Institute’s Comparative Oncology Program. It is a great model of translational research that has the potential to bring cancer treatments to patients more quickly.
Q. How many people work in your focused ultrasound research team? What is their expertise?
We maintain a team of 15 to 20 people in our laboratory. Besides the four staff members who oversee in vitro and in vivo operations, our group includes 7 senior or visiting scientists, 4 post-doctoral fellows, 4 graduate students, one programmer, and one junior specialist.
Q. Who are your internal and external collaborators?
I am currently a visiting scientist at Stanford University, and we collaborate with several Stanford scientists. We have worked with a number of different ultrasound systems and have previously developed transducer innovations with Siemens Medical Solutions. In our currently funded work, we also collaborate with scientists at Sonic Concepts, Verasonics, Cedar Sinai Medical Center, the University of Southern California, Duke University, and Emory University. Collaboration is critical, and particularly important to foster in young people, so we try hard to promote that within our group.
Q. What major discoveries/results have you achieved researching focused ultrasound?
Our laboratory has received numerous awards, including the Achievement Award from the IEEE Ultrasonics, Ferroelectrics, and Frequency Control Society, the top honor of this society. I was elected a member of the National Academy of Engineering as a result of my work on the interaction of microbubbles and ultrasound. Key work from our laboratory involves the physics of phase inversion imaging and radiation force imaging, with seminal publications in each of these areas.
Q. How does your work translate to clinical applications of focused ultrasound?
We are primarily looking at preclinical models of breast cancer and pancreatic cancer, so we hope to lead to discoveries in those areas. Our recent publication was in a mouse model of epithelial cancer.
Q. What do you see as the potential role and benefit of focused ultrasound in the treatment of cancer?
I see two major roles: the use of ultrasound to release drugs from activatable drug delivery vehicles and the use of ultrasound to ablate tumors.
Q. What are your main sources of funding?
We are primarily funded by grants from the National Institutes of Health, and we receive support from the Focused Ultrasound Foundation.
Q. What role does the Foundation play in your work?
The Foundation (FUSF) has been very supportive. I received a research award when we were developing our early drug delivery ideas, and it supports an aspect of my immunotherapy work. FUSF is playing an important role in allowing investigation of new ideas in new areas because the NIH does not fund this type of work. Getting people talking is essential, and it is doing that with workshops and events. FUSF is also asking the field to develop common methods, metrics, and models, and making sure that techniques and technologies are disseminated quickly. FUSF is doing a lot to support and promote the many exciting things happening in the field. The number of indications has grown; we now have the ability to do things in a controlled and repeatable way; and the brain applications are looking particularly compelling, as their clinical impact seems to be substantial.
Q. What did you contribute to the 2016 Focused Ultrasound Foundation/CRI Immunotherapy Summit, and what did you find helpful about participating?
We presented our work on the combination of focal therapies with immunotherapy to treat cancer, including a description of our in vitro and in vivo preclinical experiments that showed how focused ultrasound disruption could release tumor antigens or be combined with microbubbles to disrupt cell membranes and vasculature. We also described our priming protocol to achieve a complete response. We participated in discussions of preclinical models and began discussions of new projects with collaborators from Stanford.
Q. What do you say to women who are interested in Engineering?
When I went to school, I was the only woman in most of my classes. Women have made progress, but not as much as we would like to see. I would be very encouraging to other women to consider engineering as a career. In some areas, women have reached parity--at MIT, for example. Biomedical engineering is such a wonderful career--I would encourage young women to think about it.
Key Focused Ultrasound Publications
Silvestrini MT, Ingham ES, Liu Y, Fite BZ, Mahakian LM, Tam SM, Kheirolomoom A, Tucci S, Watson KD, Wong A, Monjazeb A, Hubbard NE, Murphy WJ, Borowsky AD, Ferrara KW. Priming is key to effective incorporation of image-guided thermal ablation into immunotherapy protocols. JCI Insight 2017 Mar 23;2(6):e90521.
Zhang H, Ingham ES, Gagnon MKJ, Mahakian LM, Liu J, Willmann JK, Ferrara KW. In vitro characterization and in vivo ultrasound molecular imaging of nucleolin-targeted microbubbles. Biomaterials 2017 Feb;118:63-73.
Wong AW, Fite BZ, Liu Y, Kheirolomoom A, Seo JW, Watson KD, Mahakian LM, Tam SM, Zhang H, Foiret J, Borowsky AD, Ferrara KW. Ultrasound ablation enhances drug accumulation and survival in mammary carcinoma models. J Clin Invest 2016 Jan;126(1):99-111.
Kheirolomoom A, Ingham ES, Mahakian LM, Tam SM, Silvestrini MT, Tumbale SK, Foiret JL, Hubbard NE, Borowsky AD, Murphy WJ, Ferrara KW. CpG expedites regression of local and systemic tumors when combined with activatable nanodelivery. J Control Release 2015 Dec 28;220(Pt A):253-64.
Fite BZ, Wong A, Liu Y, Mahakian LM, Tam SM, Aina O, Hubbard NE, Borowsky A, Cardiff RD, Dumont E, Ferrara KW. Magnetic Resonance Imaging Assessment of Effective Ablated Volume following High Intensity Focused Ultrasound. PloS One 2015 Mar 18;10(3):e0120037.
Kheirolomoom A, Lai CY, Tam SM, Mahakian LM, Ingham ES, Watson KD, Ferrara KW. Complete regression of local cancer using temperature-sensitive liposomes combined with ultrasound-mediated hyperthermia. J Control Release 2013 Nov 28;172(1):266-73.
Past Coverage of the Ferrara Laboratory
October 2016 FUS Immunotherapy Summit Builds on Momentum
December 2015 FUS Plus Chemotherapy Kills Cancer in Mice
May 2014 Focused Ultrasound Featured at Society for Thermal Medicine Meeting
May 2013 American Association of Physicists in Medicine Annual Meeting - Agenda
July 2010 Leading Experts Join FUS-TDD Core Stakeholder’s Group
April 2009 FUSF Funds Targeted Drug Delivery Research Project