September Research Faculty Spotlight
FAN YANG, PhD
ASSOCIATE PROFESSOR OF ORTHOPAEDIC SURGERY AND OF BIOENGINEERING
When did you become interested in biomaterials research?
I was first exposed to biomaterials research when I started my Ph.D. in Bimedical Engineering at the Johns Hopkins University. I was fascinated by the exciting prospect of repairing and regenerating human tissues using biomaterials and cell-based approaches. This sounded like a much more attractive option than metal or plastic- based medical devices/prosthetics. What was particularly attractive to me was how biomaterials could serve as a powerful tool to directly modulate biology and medicine, and offer solutions for tissue repair in a way that current treatment options cannot achieve.
Would you give some brief highlights of your research work?
FY: A bioengineer by training, I work at the interface of materials science, biology, engineering, and medicine. We are particularly interested in developing minimally invasive injectable hydrogel based therapies that can regenerate cartilage, bone, blood vessels etc. For example, our lab has invented a patented macorporous microribbon-based hydrogel platform. Unlike conventional hydrogels, the microribbon hydrogels demonstrate cartilage-mimicking shock absorbing mechanical properties, and enable fast new cartilage regeneration by stem cells in 3D with morphology and mechanical properties that mimic native cartilage. Using various animal models, we have demonstrated the potential of this microribbon hydrogel platform for regenerating various tissue types including bone, cartilage, muscle and tendon. Another major theme of our research is to apply 3D biomaterials to engineer 3D in vitro cancer models for drug discovery. For example, osteosarcoma (OS) is an aggressive bone cancer for which survival has not improved over three decades. While biomaterials have been widely used to engineer 3D soft-tissue tumor models such as breast cancer, the potential of engineering 3D biomaterials-based OS models for comprehensive interrogation of OS pathology and drug discovery remains untapped. To address this critical unmet need, we recently reported a 3D osteosarcoma model with bone matrix mimicking compositions. We showed that only our 3D OS model, but not conventional 2D culture, allowed retention of osteosarcoma signaling and drug responses in vivo. Through collaboration with clinician scientists, we are actively working on further applying such novel 3D OS model for discovering novel therapies using multiple patient-derived osteosarcoma cell lines.
How big is your research group? What can you share with our readers about the ways you run your group and motivate the students and/or postdocs, the challenges and the rewards?
My research group is composed of 15 members from diverse backgrounds including Bioengineering, Materials Science & Engineering, Chemical Engineering, Mechanical Engineering, Stem Cell Biology, and Medicine. Their diverse background provides a great niche for fostering creativity and innovation among the entire team. Research is a journey of discovering unknowns, and is filled with unexpected challenges. To make the process more fun and productive, I try to foster a supportive and collaborative lab culture. As such, each lab member not only gets feedback from me, but also from peer mentoring from other postdoctoral fellows or students. We also encourage active and dynamic discussions in lab meetings, subgroup meetings, and journal clubs. Such brainstorming process is very rewarding as it helps everyone grow together in a synergistic manner. I am very grateful that we have a wonderful group of talented people in our lab who not only help each other with research challenges, but are also a source of support and encouragement as we face inevitable challenges in life.
You have been very successful in securing research funding from highly competitive sources from both federal and private foundations. In your opinion, what are the keys to such successes?
FY: For lab PIs, getting continuous funding is one of the most important responsibilities and also the toughest job. Funding for a lab is like the fuel for a car, without which no car can run. I started actively engaging in grant writing since I was a graduate student and a postdoc, and I would encourage junior fellows/students to volunteer to help with writing fellowships/grants. If you want to learn how to drive, the only way to do it is to take driving lessons and learn from experience. Most of my grants involve clinician scientists as collaborators, who are the end users of the technologies that we develop. I make a concerted effort to seek their feedback early during the proposal development phase. Their clinical expertise is very helpful and offers complementary perspectives to help define the right problems that are not only innovative but also clinically impactful.
You mentioned about the importance to collaborate with clinician scientists. What would help foster productive collaboration between basic scientists like yourself and clinician scientists?
FY: Over the past decade, our lab has developed various biomaterials-based platform technologies that can be tailored to solve different unmet medical needs. Before we invest too much time in developing and optimizing a new technology, I would first reach out to clinician scientists in that specialty to get “user feedback”. The idea is to start with the end in mind, to validate with future clinician users on whether they believe the unmet need is indeed critical, and better understand what their wish list would be for an ideal solution. Then we go back to the lab and develop technologies further. This helps ensure technologies we develop will address high impact medical needs and make it easier for adoption by the clinicians in the end. Sometimes clinicians reach out to me with a specific medical challenge, and then we would brainstorm together to design a solution. In my experience, the most rewarding collaboration comes in when all parties are genuinely passionate about solving a research problem of common interest while bringing in complimentary expertise and perspectives.
Looking ahead, what challenges do you see in realizing the impact you would like to make through your innovative research work?
Most projects in our lab starts with materials synthesis, characterizing cell-materials interactions in vitro, and then validating them in vivo using small animal models. To realize the impact in translating these therapies from bench to bedside, it would be critical to further validate them in large animal models and move into clinical trials. These kind of translational work are usually hard to be funded through traditional grants. Looking forward, we would love to work with right collaborators and funding resources to help move these exciting new technologies forward to help patients.
Dr. Yang’s lab research was recently featured in a Stanford Podcast called "the future of everything".
August Research Faculty Spotlight
KEVIN SHEA, MD
CHAMBERS-OKAMURA ENDOWED PROFESSOR OF PEDIATRIC ORTHOPAEDICS
What are the major research themes/focuses of your laboratory?
We focus upon developing a better understanding of the pediatric musculoskeletal system, to improve our understanding of anatomy, develop/modify orthopedic surgeries to improve outcomes in young athletes with injuries.
We have developed partnerships with DVM/PhD researchers to further understand the development of the knee, blood supply of tissues, and how development/vascular supply can changes our approaches to ACL and other ligament reconstructions, Cartilage/Meniscus Repair, patella instability, and healing of osteochondritis dissecans lesions of the upper and lower extremities.
We combine anatomic research with surgical education for students, residents, fellows, surgeons to improve outcomes, develop consensus about ideal surgical techniques, and encourage creativity as we develop new, improved surgical techniques.
What is your research group/lab like?
We emphasize team building, and the development of a culture that supports education, research, and aligns with the goals of students, residents, fellows, surgeons, DVM/PhD research teams.
We encourage questions, new approaches, and novel research ideas that can come from our unique access to exceptional rare (and very valuable!) pediatric tissue.
We engage people at all levels – especially the students, new learners – who have such amazing, insightful questions for all of us to ponder.
Describe some of the interesting projects and results.
Our understanding of pediatric joints has led to new approaches for patella instability, ACL, and other ligament reconstruction.
A new understanding of pediatric meniscus vascularity and anatomy will support development of more anatomic approaches for meniscus repair, transplant, stabilization.
Our anatomic studies provide clear guidelines to surgical approaches to smaller pediatric knees, with open growth plates. These studies will guide surgeons to safer surgical approaches to complex problems and lower the risk of neurovascular injury, growth plate compromise, and other complications.
What was your biggest challenge in research?
Obtaining access to adequate amounts of pediatric tissue to support a sustained, prolonged research program has been one of our historic and future challenges.
As interest in our research program has grown from 3 to over 50 individuals, we are looking for opportunities to continue our educational/collaborative research programs and continue to provide access to a growing number of those interested in being part of this program.
How did you get interested in research?
I enjoyed playing with motor, electronics, engines as child – always looking to modify these to improve performance. I think of research as an exploration tool to identify new problems, ask questions, and try to improve outcomes.
What is your favorite part of the job?
Asking Questions, responding to questions, and continuing to learn from the students, resident, fellows, surgeons, DVM/PhD researchers who challenge us, push us to get better. The ongoing list of research questions, opportunities that we see every year inspire us on this journey.
Allowing students, residents, fellows, young faculty to become actively involved in research, publications, and careers in academics.
Baskar, Danika, Tyler J. Stavinoha, Mark Sanchez, Anshal Gupta, Sahej D. Randhawa, Matthew S. Rohde, Brian Vuong et al. "Quantifying the Relationship Between the Medial Quadriceps Tendon–Femoral Ligament and Patellar Borders: A Pediatric Cadaveric Study." The American Journal of Sports Medicine (2022).
Tran, Emily P., Aleksei B. Dingel, E. Bailey Terhune, Nicole A. Segovia, Brian Vuong, Theodore J. Ganley, Peter D. Fabricant, Daniel W. Green, Tyler J. Stavinoha, and Kevin G. Shea. "Anterior cruciate ligament length in pediatric populations: An MRI study." Orthopaedic Journal of Sports Medicine 9, no. 4 (2021): 23259671211002286.
Shea, K. G., Milewski, M. D., Cannamela, P. C., Ganley, T. J., Fabricant, P. D., Terhune, E. B., ... & Polousky, J. D. (2017). Anterolateral ligament of the knee shows variable anatomy in pediatric specimens. Clinical Orthopaedics and Related Research®, 475(6), 1583-1591.
Gadinsky, Naomi E., Kenneth M. Lin, Craig E. Klinger, Jonathan P. Dyke, Laura J. Kleeblad, Kevin G. Shea, David L. Helfet, Scott A. Rodeo, Daniel W. Green, and Lionel E. Lazaro. "Quantitative assessment of the vascularity of the skeletally immature patella: a cadaveric study using MRI." Journal of Children's Orthopaedics 15, no. 2 (2021): 157-165.
Stavinoha, T. J., Randhawa, S., Tompkins, M., Ellis, H., Ganley, T., & Shea, K. G. (2021). THE EXTENT OF MEDIAL QUADRICEPS TENDON FEMORAL LIGAMENT (MQTFL) PATELLAR AND QUADRICEPS ATTACHMENT: A PEDIATRIC CADAVERIC STUDY. Orthopaedic Journal of Sports Medicine, 9(7_suppl3), 2325967121S00104.
Randhawa, S., Tran, E., Segovia, N. A., Ganley, T., Tompkins, M., Ellis, H., & Shea, K. G. (2021). Epidemiological Study of the Discoid Meniscus: Investigating Demographic-Based Predictors in Large-Scale Claims Database. Cureus, 13(11).