What is the current focus of your research, what is the most exciting aspect of your work, and what do you find most rewarding about your work?
The focus of my research is, in a word, blindness. Work in the lab ranges from basic research on molecular mechanisms of retinal development to more translational efforts to develop stem cell-based therapies for ocular disease, especially age-related macular degeneration (AMD). There are few effective treatment options for most patients afflicted by this horrible disease, a leading cause of blindness. I’ve always been interested in developmental biology, with the thinking that if we can understand that process, maybe we can kick-start developmental programs to regenerate and treat disease and injury. Dysfunction of retinal pigmented epithelial (RPE) cells causes AMD, and my lab at UC Santa Barbara developed protocols to generate RPE from pluripotent stem cells.
One day at a meeting in Newport Beach, in the lobby of the hotel, I met Mark Humayun, a retinal surgeon from USC, and, with Mark’s leadership, we began to build a team that included surgeons, stem cell biologists, bioengineers, and retinal cell biologists. With David Hinton (USC), Linc Johnson (UCSB) and Jane Lebkowski (Regenerative Patch Technologies) we started the California Project to Cure Blindness, and obtained funding from the California Institute for Regenerative Medicine (CIRM) to move the research from bench to bedside, (or in our case, perhaps, from beach to bedside?). We assembled a dream team of experts from USC, UC Santa Barbara, Caltech, and City of Hope, and also collaborated with Pete Coffey at University College London (and recruited him to UC Santa Barbara, where lives on a boat). Our strategy has been to grow a monolayer of polarized RPE on a synthetic scaffold and implant it in the back of the eye to replace dying RPE cells in patients. We are now in a phase 1 clinical trial, with some promising results, and are now planning a larger, phase 2 trial.
With training in biochemistry and cell biology, I never thought I would be involved in a clinical trial. But it has been exciting and rewarding to see the translation of basic science to the clinic, where we might contribute to helping people. Patients that volunteer for clinical trials are my heroes; they are like ocular astronauts, willing to venture into the unknown. And people afflicted with blinding diseases are like rocket fuel for the lab, motivating us to work harder.
Most rewarding single event: recently, at the ISSCR meeting, my lab met Anna Kuehl , a patient in our phase 1 trial whose vision improved after therapy. She wanted to thank each one of them individually.
What led you to become a scientist and to stem cell research? Do you have any mentors or individuals who have inspired you in your stem cell work?
I developed a deep fascination for the outdoors and biology as a kid growing up in Minnesota. I was thinking about marine biology or forestry for a career, but when I took biochemistry, I changed my mind. I discovered that biochemistry is the foundation of all biology – it explains everything. Plant biochemistry was the focus of my undergraduate research at UC Davis with Eric Conn, where I found that I loved tinkering in the lab. That was followed by doctoral studies on bacterial chemotaxis at UC Berkeley with Dan Koshland, and then developmental neurobiology at UCSF with Louis Reichardt. My lab at UC Santa Barbara focused on the development of the retina and retinal disease for many years, but when Jamie Thomson’s picture appeared on the cover of Time magazine for the discovery of human embryonic stem cells, I grew interested in their potential for treating disease. My lab started working in earnest on deriving retinal cells from hESCs in 2004, with training from Wicell, some crucial help and advice from the Thomson lab, and funding from CIRM.
What guidance would you share in talking with trainees interested in pursuing your area of research? What do you most value about your membership with the ISSCR?
Big gains in knowledge often require interdisciplinary teams of researchers. Collaborate rather than compete if you can; build teams. ISSCR can help. At the next ISSCR meeting, challenge yourself to reach out to a colleague and establish a new collaboration.
How do you spend your free time? What is something your peers would be surprised to learn about you?
I still love the outdoors and try to get out on the bike every morning. I still love marine biology and try to get into the ocean as often as I can. I am co-founder of a biotech startup, I volunteer on archaeological expeditions, and I’m training to be a volunteer fireman.
I have a taxidermied bear on a surfboard in my living room, but that may not surprise anyone who knows me.