Working alone, a scientist or university can only make so much progress in finding answers to basic questions or new treatments for diseases ranging from HIV to cancer to diabetes. That’s why nearly 300 scientists from USC, UCLA and UCSF gathered in Santa Barbara for a Tri-institutional Stem Cell Retreat.
Hosted by USC at the Fess Parker: A Doubletree Hilton Resort from May 17–19, the retreat showcased some of the most innovative projects from the three universities’ stem cell research centers — which were all established with support from Eli and Edythe Broad and the California Institute for Regenerative Medicine (CIRM).
Andy McMahon, director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, opened the event with a clear articulation of its purpose: “If we want a true measure of success for the meeting, it won’t simply be that we’ve had a good time, but that the scientific interchange between us provides new insights into each of our own specific interests, and new collaborative opportunities emerge as a result.”
Francesca Mariani, the lead organizer from USC, added that these collaborations have the potential to “bring our work at the bench closer to the clinic.”
Holger Willenbring, the lead organizer from UCSF, and Hanna Mikkola, the lead organizer from UCLA, both commented on the tremendous value of the three institutions coming together to share their research.
Willenbring said: “I really enjoy the tri-institutional thing, because it’s very uncommon. This is a very open meeting. There’s good exchange.”
Mikkola added: “Everybody’s just putting their best stuff forward, and everybody’s talking about unpublished, honest, new data.”
Keynote speaker Amy Wagers from the Harvard Stem Cell Institute detailed her quest for the “fountain of youth” by reversing the dysfunction of stem cells in aging tissues such as muscle. In a striking experiment, Wagers connected the circulatory systems of an old mouse and a young mouse. The old mouse experienced several “youthful” benefits, including a decrease in abnormal heart enlargement and an increase in the regeneration of muscle, neurons and the insulin-producing “beta cells” of the pancreas. Conversely, the young mouse suffered certain ailments of age, including a decrease in the regeneration of muscle, neurons and beta cells. Wagers’ eventual goal is to find ways to use some of these “youthful” blood-borne factors to treat age-related dysfunction.
Wagers engaged with her California colleagues throughout the retreat. “I’ve enjoyed myself very much,” she said. “What I’ve found valuable about the experience is really the breadth of science that has been discussed here and the paralells that one can draw between different stories. And it’s been incredibly intellectually stimulating, and I feel very honored to be a part of it.”
Throughout the retreat, principal investigators (PIs), postdoctoral scholars and PhD students from the three institutions discussed advances relevant to a wide variety of diseases.
As the leading cause of death in the Western world, heart disease was the topic of several talks. USC PI Megan McCain discussed how she engineers micro-scale mimics of human tissues called “hearts on chips,” which enable scientists to study diseases and screen drugs. USC postdoctoral scholar Michaela Patterson presented her hypothesis that multiple genes dictate the number of regenerative heart cells, called “mononuclear diploid cardiomyocytes,” that are present in a mammalian heart. UCLA PI Arjun Deb described how some scar-forming “fibroblast” cells have the ability to become blood vessel-forming “endothelial” cells, which boost the ability to heal after a heart attack. UCSF/Gladstone PI Deepak Srivastava discussed ways to reprogram cells as a potential treatment for heart disease.
Srivastava enjoyed the opportunity to connect with scientists studying the heart as well as other organ systems. “Being able to learn what other people are doing in their own systems that you might be able to leverage for your own studies is of tremendous benefit,” he said. “And all being within California, it’s easier to develop those collaborations from a physical distance standpoint. So I found that very useful.”
Another aspect of the cardiovascular system, the blood, was also a popular topic. UCLA PI Donald Kohn discussed curing children with a lethal form of immune deficiency, known as “bubble baby” disease, through correcting the genes in their blood stem cells. Kohn is using the same approach to develop a clinical trial addressing sickle cell disease. His PhD student Aaron Cooper discussed improving methods for gene therapy targeting these stem cells.
Cancer was another common theme among the presentations. UCLA senior scientist Deanna Janzen talked about approaches to targeting ovarian cancer stem cells. UCLA PhD student Drake Smith discussed genetically engineering blood stem cells to form a type of immune cell called “invariant natural killer T cells,” which could potentially fight lung cancer.
UCLA PI John Chute also addressed blood stem cells with a focus on their microenvironments. His goal is to develop stem cell therapies for malignancies and other diseases.
“This retreat is the best collection of all the best minds in stem cell research in California,” said Chute. “I mean, to me, it’s the audience we like to present our work to. Not only that, there are a lot of young people, who are the kind of people we love to engage and collaborate with. Young people bring open-mindedness that’s different. It’s fun to present your work to this kind of community.”
Owen Witte, director of UCLA’s stem cell research center, discussed the stem cell nature of neuroendocrine prostate cancer.
“The breadth of what’s presented is impressive,” said Witte, “and it’s impressive because it influences other people in other areas to think differently when they see science from a broad palette as opposed to a very narrow perspective.”
Gay Crooks, co-director of UCLA’s stem cell research center, added: “It’s three great insitutions doing fantastic cutting-edge work in stem cell science. And we have always had a lot to learn from our colleagues in science everywhere, but especially when we’re local in California.”
Several neural researchers also shared their findings. UCSF PI David Rowitch presented a cell-based therapy for hypomyelinating leukodystrophy, a fatal disorder in which the brain’s white matter degenerates leading to loss of muscle function, sight and hearing. USC PI Michael Bonaguidi highlighted neural stem cells, USC postdoctoral fellow Kate Galloway discussed reprogramming skin cells into neurons, and USC postdoctoral fellow Suhasni Gopalakrishnan talked about converting skin cells into the sensory cells of the inner ear.
Gopalakrishnan commented on the value of interacting with the wider stem cell community: “At least when I’m in the lab, I tend to think about it just from the reprogramming perspective, and it helps us think about other kinds of regenerative models — and there are so many regenerative systems in the human body.”
Continuing the conversation about the body’s sensory organs, USC PI David Hinton summarized the plans for an upcoming phase 1 clinical trial to treat age-related macular degeneration, the leading cause of blindness in the elderly in the Western world. A partnership with USC colleague Mark Humayun and collaborators at UCSB, Caltech and the City of Hope supported by nearly $40 million in funding from CIRM, the trial uses stem cells to produce some of the key cells that help people see — known as “retinal pigment epithelial cells.”
UCLA PhD student Yingqian Peng enjoyed Hinton’s talk. “Some of the work inspired me,” she said. “I’m very happy to be here.”
Hinton appreciated that the retreat created opportunities for students and postdoctoral fellows to meet more established PIs. “This is such a comfortable meeting with a good amount of chances for interaction, and it’s great to meet the students from the different labs that are very active and want to participate,” he said. “Last night, I was so impressed. Everybody was around and talking about their work, and there was a real sense of excitement about the future of stem cell research.”
UCSF PI Sarah Knox gave a different perspective on the role of the parasympathetic nerves — which send signals that guide the formation and regeneration of certain organs, such as the intestines, trachea, prostate, salivary glands and others.
Several researchers also shared their progress in tackling diseases of the digestive system. To address the diabetes epidemic, UCSF PI Julie Sneddon, UCSF PI Matthias Hebrok and UCSF postdoctoral scholar Holger Russ all discussed ways to turn stem cells into the insulin-producing “beta cells” required to regulate blood sugar levels. Tracy Grikscheit, a PI at Children’s Hopital Los Angeles and USC, talked about her work in intestinal regeneration as a treatment for Short Bowel Syndrome, a cause of mortality in infants. UCSF postdoctoral scholar Johanna Schaub discussed how to build a functional liver system from cells called hepatocytes.
McMahon addressed adult kidney repair and its similarities to normal kidney development. Twenty-six million Americans suffer from chronic kidney disease, and many die as a result of the shortage of organs available for transplant.
Two presentations addressed the skeletal system. USC PI Gage Crump tackled the topic of repairing bone fractures resulting from everything from car accidents to gun shot injuries. USC PI Yang Chai described a special population of so-called “mesenchymal stem cells” that maintain and repair the skull. These stem cells could potentially be used to treat babies who suffer from fused skull joints, which constrict the developing brain and disrupt vision, sleep, eating and IQ.
USC PI Paula Cannon shared her progress in developing next-generation tools to genetically edit blood stem cells as a treatment for HIV, immune deficiencies and blood diseases. Cannon and her colleagues have already developed one gene editing tool that could potentially cure HIV/AIDS by introducing a mutation in a gene called CCR5 that confers natural immunity to HIV. Heading into clinical trials, the approach is inspired by the “Berlin patient,” a man cured of both HIV and leukemia through a bone marrow transplant from a donor with a CCR5 mutation.
“This three institution meeting is really showcasing what powerhouses USC, UCLA and UCSF are, and what leaders they are in the whole field of regenerative medicine,” she said.
UCLA postdoctoral fellow Konstantinos Chronis and UCSF postdoctoral scholar Aydan Bulut-Karslioglu explored how genes are either “turned on” or “turned off” through a process called epigenetic regulation, which can influence a stem cell’s potential to become any type of cell. UCLA PI Amander Clark discussed epigenetic regulation in the context of human sperm and eggs.
Several other scientists shared their highly diverse projects related to stem cell biology. USC PI Scott Fraser discussed tools everyone can use — the latest generation of microscopes and imaging tools. UCSF postdoctoral fellow Ripla Arora talked about changes in the lining and glands of the uterus while the embryo implants and develops. UCLA PI Brigitte Gomperts shared research about genes that regulate stem cells in the airways of the lungs. UCSF PI Jason Pomerantz explored the complex question of whether or not suppressing tumors also suppresses regeneration.
“The retreat’s great,” said Pomerantz. “It’s a nice environment to get the three insitutions together and to share science outside of our immediate colleagues who we usually talk to every day and have a little bit of a broader interaction. It develops some good relationships.”
Nearly 100 additional scientists presented their research on posters, and 10 of these gave brief “poster highlight” talks.
“I really like the fact that — even compared to previous retreats — it’s been very diverse topics-wise,” said UCLA postdoctoral fellow and poster presenter Rafael Demarco. “And we’ve been learning a lot about so many different systems. And the quality of the presentations just has been very spectacular.”
UCSF postdoctoral fellow Laralynne Pryzbala, whose work addresses how mechanical forces control stem cell differentiation, won the prize for best poster.
“I’m an embryonic stem cell biologist, but there are people studying stem cells from all different types of organs, so it really gives a good overview of what people are doing in other stem cell fields,” she said. “I’ve been able to meet a lot of people, and so that’s been really nice, and people from other instutitons, too. I’m not as familiar with the stuff out of UCLA and USC, so it’s really cool to see that.”
UCSF PhD student Terren Niethamer mentioned that there “have been lots of good networking opportunities.”
USC PhD student Cynthia Neben added: “For me, it’s great, because I want to stay in California for postdoc.”
The scientists also relaxed during more casual activities, such as a speed networking cocktail hour, hot topics lunch discussions, a scavenger hunt, a beach volleyball game and more.
“It’s a really nice location,” said USC PhD student Marie Rippen. “I was glad to see that a lot of people participated in the volleyball, and the hot topics were cool. There are enough breaks that are interspersed, and there’s a good mix of PIs and postdocs that are speaking. So it’s nice to be able to hear somebody talk and then have the opportunity at the coffee break or lunch to go discuss their research with them.”
The retreat received generous support from: Eli and Edythe Broad; title sponsor Amgen; platinum sponsor Gibco by Thermo Fisher Scientific; gold sponsors CIRM and Cellular Dynamics International; silver sponsors Affymetrix, Fluidigm, Genea Biocells, Genentech, Leica Beckman Coulter, and Sanofi; and bronze sponsors Bio-techne, Eppendorf, and NuGEN.
McMahon concluded the meeting by expressing his hope that the three institutions would repeat the experience next year.
“I’ve learned so much from this meeting,” said McMahon. “It’s a rapidly moving field, so I think we need a retreat next year as well.”
To view more photos from the retreat, visit flickr.com/photos/106541334@N04/sets/72157652753693109.