Following the grant award, the training program successfully appointed eight graduate students, four postdoctoral fellows and one clinical fellow. Appointment followed a campus-wide call for applications and a holistic review process in which we aimed to appoint trainees from a broad-range of backgrounds and scientific disciplines. In this we believe we believe we were greatly successful. Following appointment of trainees, we have organized a number of cohort-building activities culminating in a now to be annual retreat. Attendance at the retreat was compulsory for both trainees and mentors and this policy was adhered to with some understandable exceptions where a prospective attendee had a previous engagement, e.g. an international meeting. One notable outcome of the retreat was the realization of the potential for collaborative projects between training labs. Another important outcome came from an open discussion about improving trainee outcomes and is a subject that the program directors will act on. Following the grant award, the training program successfully appointed eight graduate students, four postdoctoral fellows and one clinical fellow. Appointment followed a campus-wide call for applications and a holistic review process in which we aimed to appoint trainees from a broad-range of backgrounds and scientific disciplines. In this we believe we believe we were greatly successful. Following appointment of trainees, we have organized a number of cohort-building activities culminating in a now to be annual retreat. Attendance at the retreat was compulsory for both trainees and mentors and this policy was adhered to with some understandable exceptions where a prospective attendee had a previous engagement, e.g. an international meeting. One notable outcome of the retreat was the realization of the potential for collaborative projects between training labs. Another important outcome came from an open discussion about improving trainee outcomes and is a subject that the program directors will act on. Students are required to participate in our monthly Stem Cell Seminar Series during Fall and Winter Quarter, where they attend a distinguished guest speaker’s seminar on their current research and are given the opportunity to meet and have lunch with the speaker. During their Spring Quarter of their first or second-year on the training program, students are required to enroll in Molecular Biology (Mol Bio) 243, Topics in Stem Cells, presentation by participating faculty or guest lecturer that is open to the science community, followed by discussion of the lecture topic or a related topic. Finally, students are required to have taken Microbiology and Molecular Genetics (MMG) 250, Conduct of Research, where each session includes a formal presentation by faculty/invited speaker followed by a discussion of case studies related to the topic under consideration. This course is usually taken during a graduate student’s Gateway program and fulfills this requirement. Additionally, our students are invited to applicable seminars and workshops presented by other UCI departments. These events can improve their understanding of their research from a different lens or provide different career pathways that were not completely realized until attending the event.
During the review period, one trainee published a paper describing the role for membrane-bound receptor, PIEZO1, in the development of neuronal cells in the brain. PIEZO1 modulates the quantity, quality, and organization of cells by influencing cellular cholesterol metabolism. The study established a direct link in neural development in neural stem cells for a role for the PIEZO1 receptor and intracellular cholesterol levels, These studies have important implications for human brain development and how cholesterol may play a part in this process in health and disease. Another trainee published a paper about neuronal support cells termed microglia. The findings of their studies, carried out in a well-tested animal model of Alzheimer’s disease (AD), indicated that microglia help prevent some of the pathological changes associated with some forms of AD. These studies also indicated that one of the main AD risk genes actually affects microglia and not neurons, suggesting that new treatments for AD might involve treating cells other than neurons in the brain.
In summary, our trainees have made some important scientific discoveries and have made much progress in furthering their career goals. We strongly believe this training program will further the goals of the California Institute of Regenerative Medicine and help develop new stem cell based treatments for human diseases and disorders.
Reporting Period:
Year 2
The CIRM Scholars program is now completing its second year. Currently we have 11 graduate students, 2 postdoctoral fellows and 2 clinical fellows appointed to the program and here we are reporting on them and another 7 trainees that completed the program - a total of 18 trainees. Our trainees have made enormous progress towards the goal of developing the next generation of researchers for the stem cell field. As part of their training, students are required to participate in our monthly stem cell research Seminar Series during Fall and Winter Quarter, where they attend a distinguished guest speaker’s seminar describing their latest research. In addition, they are given the opportunity to meet and have lunch with the speaker where they discuss such topics as their latest scientific results, their career goals and hear how leading scientists in the field have successfully navigated important issues in their careers. During their Spring Quarter of their first or second-year on the training program, students are required to enroll in “Topics in Stem Cells”, which entails a presentation by participating faculty or guest lecturers that is open to the science community, followed by discussion of the lecture topic or a related topic. All trainees are required to have taken a course entitled “Responsible Conduct of Research”, where each session includes a formal presentation by faculty/invited speaker followed by a discussion of case studies related to the topic under consideration. This course is usually taken during a graduate student's first year. Additionally, trainees are required to attend applicable seminars and workshops presented by their own home departments. Together, these events prepare trainees at all levels for an independent career in research or other areas related to success in the stem cell and regenerative medicine field such as patent law, regulatory practice, clinical trials, translational research and product development, etc. Our goal is to improve our trainees' understanding of their research with a different lens or provide different career pathways that were not completely realized until attending the event.
One major outcome of our training program has been in the advancement of the careers of our trainees. Several trainees have been awarded fellowship and honors reflecting the science or commitment to outreach and diversity. We encourage our trainees at all levels to obtain their own funding as a route towards independence. This past year several of our trainees have obtained fellowships or awards or have secured positions. For example, one of our postdoctoral fellows obtained a fellowship from a long-established charitable foundation that supports research on neurodegenerative disease and a graduate student won an individual F31 fellowship from the NIH. One of our clinical trainees is moving on to the clinical phase of study in dermatology. Our trainees have published 15 articles describing strong advances in stem cells and regenerative medicine. These articles have appeared in outstanding venues,, including in Nature (2), Nature Genetics, Developmental Cell, Cell Reports, EMBO Molecular Medicine, and Development.
In summary, our trainees have made some important scientific discoveries and have made much progress in furthering their career goals. We strongly believe this training program will further the goals of the California Institute of Regenerative Medicine and help develop new stem cell based treatments for human diseases and disorders.
Grant Application Details
Application Title:
CIRM Scholars Comprehensive Research Training Program
Statement of Benefit to California:
A primary goal of Proposition 14 is to continue to translate basic stem cell research to clinical applications. The disability and loss of personal freedom and earning power resulting from a disease or disorder are devastating and create a financial burden for California in addition to the suffering caused to patients and their families. Therapies using stem cells have the potential to change millions of lives. Using stem cells as models of disease will help us understand the underlying causes of disease and likely aid in the development of drugs to treat those diseases. For the potential of stem cells to be realized, California researchers need the personnel to develop them into viable treatments. Therefore, the raison d’etre for the proposed program is to provide training to the next generation of researchers in stem cell biology, gene therapy and regenerative medicine capable of advancing the development of new methods of treating human disease. The breadth and depth of the stem cell biology, gene therapy and regenerative medicine research programs, which have already made important advances and secured significant funding from CIRM, will act as the core around which all training will be organized. Anticipated benefits of our Training Program to the Citizens of California include: creation of a training program that will attract the best and brightest minds to the state; development of new cell-based treatments for a variety of diseases and disorders; generation of new techniques for using stem cells (and derived cells) to deliver drugs or other agents to tissues, thereby developing new treatment methods; development of methods of using gene therapy to treat human diseases; improved methods for understanding normal development and environmental risks to the early embryo; improved methods for detecting and understanding effects of toxicants in the environment and workplace; improved clinical trial methodology that will directly impact human testing of stem cell and gene therapies; development of new improved methods for developing and testing drugs for treating disease; transfer of new technologies and intellectual property to the public realm with resulting IP revenues coming into the state; creation of new biotechnology spin-off companies based on generated intellectual property; creating interdisciplinary research teams that will have a competitive edge for obtaining funding from out of state; development of researchers and clinicians that will establish clinical research programs in the state; and, creation of new jobs in the biotechnology sector. It is anticipated that the return to the State in terms of revenue, health benefits for its Citizens, job creation, and revenue, will be significant in the long term.
