Training Program in Stem Cell Research
Our goal is to continue the Type I CIRM-funded Comprehensive Training Program that was established at this institution nearly 3 years ago. Specifically, we want to support 6 graduate students, 6 postdoctoral (Ph.D.) fellows, and 4 clinician-scientists (M.D. and or Ph.D.). We provide a unique training environment for students at all levels who are pursuing careers in regenerative medicine. Specifically, our institution offers a world-class research training experience in the context of an equally prestigious medical school and clinical enterprise. We are also noted for our faculty, a diverse and talented group of individuals—1,500 full-time members who are renowned for their dedication to the training process. Additionally, this institution has a long history of supporting human embryonic stem cell research within a framework of the highest ethical standards of conduct. In this productive research environment, our regenerative medicine institute fosters work toward regenerative medicine therapies. The regenerative medicine institute has 7 pipelines that are designed to promote the development of cell-based therapies for repair/regeneration of cardiovascular, neural, pancreas and liver, hematopoietic, musculoskeletal, epithelial, and reproductive tissues. Each pipeline integrates the research of numerous investigators who are working together to translate basic research discoveries into clinically viable therapies. The pipelines are supported by programs that cut across several disciplines, including Human Embryonic Stem Cells, Cancer, Immunology, Genetics, and Bioengineering. Regenerative medicine institute research is supported by key technology core facilities. Additionally, we were awarded a grant to build and run a CIRM Shared Laboratory and Teaching Facility that will be an important resource for our trainees and a CIRM Major Facilities Award that will allow consolidation and expansion of stem cell-related activities in a new building. With regard to campus-wide events, the regenerative medicine institute sponsors many well-attended series, including regularly scheduled seminars, journal clubs, a young-faculty forum, and an annual retreat. These events take place against a backdrop of stimulating activities with similar formats in other programs that cover cutting-edge research developments in the U.S. and around the world. In this context, CIRM trainees at this university will have several different types of learning experiences that include formal courses in stem cell biology and related topics such as human development and cell biology. Ethical issues will be addressed in a course that is solely devoted to this topic. Trainees will also do research with world-class mentors who focus on transforming basic research discoveries into clinical applications. Thus, this university provides an exceptional and exciting environment for trainees who will be the next generation of leaders in the field of regenerative medicine.
We envision that the citizens of the state of California will benefit in many ways from continuing this institution’s Comprehensive Training Program for graduate students, postdoctoral fellows (Ph.D.), and clinician-scientists (M.D. and/or Ph.D.). Collectively, the basic research, translational strategies, and clinical therapies that will emerge from the work of this university’s California Institute for Regenerative Medicine (CIRM)-funded trainees will be an important stimulus to the state economy, particularly the biotechnology sector and associated medical enterprises. Additionally, specific groups of individuals will directly benefit from work that is focused on cell-based therapies for repairing tissues and organs whose damage leads to common medical conditions, such as diabetes, cardiovascular disease, Parkinson’s disease, paralysis and/or immune dysfunction. On the way to achieving the CIRM’s ultimate goals in terms of novel regenerative therapies for patients, we envision that numerous other benefits will emerge. For example, human embryonic stem cell (hESC) systems are powerful tools for unraveling the molecular bases of human development, which remain largely a black box. A fundamental lack of understanding regarding the mechanisms that give rise to the hundreds of cell types that form tissues and organs makes it extremely difficult to discern why these processes sometimes go awry, leading to birth defects and/or setting the stage for many diseases. Additionally, it is likely that novel therapies for other medical conditions will emerge. In this regard, some forms of cancer are now thought to be associated with the proliferation of stem cells that carry mutations in genes that promote their self-renewal rather than differentiation and integration into the compartment that they normally occupy. Other important applications include drug development. For example, hESCs and their differentiated progeny could be used to screen lead compounds for efficacy, safety and/or toxicity. Where will the workforce come from that will enable this revolution in how the medical establishment approaches patient care? Given the fact that hESCs were first described just 10 years ago, this is a very young field that must be rapidly populated with scientists and clinicians who are specially trained in all aspects of regenerative medicine, a new specialty. This necessity makes the funding of CIRM-sponsored training programs especially critical for institutions such as ours that have the ability to make important research discoveries and translate them into clinical therapies. In this regard, our university has a long and distinguished history of training leaders in science and/or medicine who easily traverse the boundaries between academia and industry. Our past successes strongly suggest that our CIRM-funded training programs will be equally successful. Accordingly, we expect that our trainees will become leaders in the field.
This training grant is a very valuable asset to a broad range of UCSF programs. The resources that are made available to our Scholars enrich graduate education and the training experiences of the postdoctoral and clinical fellows that are supported under this mechanism. A description of the various components of our training program follows.
The process of securing a CIRM-sponsored fellowship at UCSF is very competitive. We work extremely hard to make sure that open positions are widely advertised to our various constituencies. These include the many graduate groups, the departments with which they are affiliated and the clinical training programs. Announcements are made through several routes including LISTSERVES and in person at seminars, journal clubs, workshops and retreats.
We know that a strong, fair and open application process is key to recruiting truly outstanding trainees. One aspect is making sure the applicants have sufficient time to prepare outstanding proposals. Therefore, the announcement of vacant positions is made at least four weeks before the application due date. The proposal has several components, including a three-page research plan, a mentor training plan/letter and biographical sketches from the applicant and his/her Principal Investigator. We ask for two additional reference letters from individuals who know the prospective Fellow well, and can make detailed comments about their past accomplishments and future potential. A committee consisting of UCSF scientists, who broadly represent the major stem cell research pipelines at this university, reviews the applications. Two individuals provide written critiques and scorers for each application. Thus, we use objective criteria to choose the Scholars.
Our trainees take advantage of the numerous and varied stem cell-related activities that are sponsored by this program and available at UCSF. This year we started a new activity, CIRM Scholar Lunches. These meetings are designed to bring the pre-doctoral students, postdoctoral fellows and clinical fellows that this training grant supports together with the leadership of the program. We allot time for general discussions and to cover special topics. During the past year the latter included ethical issues in stem cell biology, careers in the biotechnology sector, obtaining venture capital for start-ups, licensing and patenting.
The Scholars also attend local, national and international meetings. The CIRM annual meeting is a popular event that brings them together with trainees and their mentors from other universities. This is a valuable opportunity for scientific interchange and networking. Many also attend the annual meeting of the International Society for Stem Cell Research, which is an exciting opportunity to meet the thought leaders in many branches of stem cell science. The other meetings they attend are usually more specialized, focusing on their particular areas of research.
At UCSF they take advantage of many retreats that are held annually. Examples include those that are sponsored by the Biomedical Sciences Program, The Developmental and Stem Cell Biology Program and the Program in Biomedical Sciences. They also attend lectures that are part of the 11 regular seminar series at this university. Some are entirely focused on topics in stem cell biology and others include speakers who work in the field. The Scholars also participate in Journal Clubs, where exciting new publications are discussed and in Workshops, where they have an opportunity to present work in progress and receive feedback from the students, fellows and faculty who attend.
They also take formal courses or audit these offerings. Some are specially designed for stem cell trainees such as Developmental and Stem Cell Biology, which integrates fundamental concepts in these fields. They also take the one-week Stem Cell Biology course that is offered by the UCSF CIRM Shared Lab and Teaching Facility, which has both a lecture in the laboratory component. They also participate in a course that addresses ethical issues in stem cell biology research. On an individual basis they attend more specialized courses that are specially tailored to their fields of study.
Program administration is directed by the Principal Investigator and the Co-Principal Investigator, Dr. Robert Blelloch, a physician and scientist. A strong oversight committee, consisting of prominent UCSF stem cell scientists, helps manage this important resource. A talented staff handles financial and other administrative aspects of the training grant.
In summary, we have designed a training program with maximal benefits to our CIRM Scholars. As a group, they have gone on to many types of careers in the stem cell sciences. They have taken jobs in the biotechnology sector and in academia. We think that their training experiences at UCSF have given them a very strong foundation on which to build successful careers.
The UCSF CIRM training grant is a critical component of graduate and postgraduate education at this institution. This unique resource enables the training of individuals who will go on to basic research in a laboratory setting. The diverse nature of our faculty mentors assures that equal importance is given to educating trainees who are interested in translating research findings into clinical therapies. As a group, our past and current trainees include top tier young investigators in the field of regenerative medicine.
Our CIRM Scholars enter the program following a rigorous selection process. Open slots are widely advertised 4-6 weeks prior to the due date. The mechanisms include the listservs of our graduate programs, clinical chairs and The Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research at UCSF. Current mentors and trainees are ambassadors for our program. The application process is designed to be rigorous and fair. Prospective trainees write a three-page research plan, which is accompanied by the mentor’s individual training program and three letters of reference. This material, and the biographical sketches of the student and faculty member, provide a very complete picture of the applicant’s past accomplishments, planned experiments and future potential, information that is key to the integrity of the selection process. Reviews are conducted by an experienced faculty committee representing the broad range of stem cell-related activities at this institution. Formal written critiques are prepared and numerical scores given, which enable ranking. Many applicants apply. As a result, our trainees are from the top echelon.
As to Program activities, UCSF offers an outstanding environment for stem cell and regenerative medicine research, in general, and our CIRM trainees in particular. This includes a dozen formal seminar series. They also attend the Stem Cell Journal Club, a discussion of high profile recent papers, and the Stem Cell Workshop, where they present work in progress. Every major program at UCSF holds an annual retreat. Our CIRM Scholars are required to attend one of these events. Finally, they use their travel allowances to attend national and international meetings on various topics in the fields of stem cell and developmental biology, as well as more clinically oriented symposia as related to regenerative medicine therapies. This year our Scholars had the added benefit of attending the Third Annual Tri-Institutional Stem Cell Retreat that included speakers from UCSF, UCLA and USC. We also sponsor lunch-time get-togethers for all trainees, which are led by the Program Director. This venue is a valuable forum for research presentations and discussions, for example, ethical issues and career counseling.
The courses that our trainees take depend on their educational level. Graduate students are enrolled in formal instruction; the exact components of the curriculum depend on the program, most commonly Biological Sciences, Biomedical Sciences or Developmental and Stem Cell Biology. As their research interests mature, they sometimes seek additional coursework, for example, in computer programming. The postdoctoral fellows and physician-scientists tend to have completed their coursework and focus on research. However, (along with the graduate students) they participate in the program activities. They are required to take classroom instruction regarding the Responsible Conduct of Research and Ethical Issues as Related to Stem Cell Research. In addition, several elect to take our CIRM Shared Laboratory Training Course, and attend lectures in the graduate courses that are relevant to their research.
Our CIRM training grant benefits from having a very capable administrative head who works with additional staff in the office of The Eli & Edythe Broad Center for Regeneration Medicine and Stem Cell Research at UCSF. The chief administrator assists the Program Director in all aspects of the day-to-day operations of the training grant. He monitors upcoming openings in the program and works with the Principal Investigator to strategize efforts to effectively and efficiently select new trainees. He also processes all appointments, renewals and terminations for the CIRM Fellows. He serves as a liaison between trainees, CIRM and institutional offices. Although not his primary duty, he helps the Program Director manage the financial aspects of this grant, which are handled by the office of The Broad Center. Our governance structure includes an Oversight Committee with members who are leaders in stem cell research and regenerative medicine.
In summary, our training program has been very successful. We are producing the next generation of leaders in stem cell/developmental biology and the translational and therapeutic applications that are emerging from these fields. Thus, our CIRM scholars are fueling the pipeline that will deliver stem cell-based therapies to the citizens of California.
- Nature (2014) Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells. (PubMed: 24413397)
- Nat Cell Biol (2014) The chromatin regulator Brg1 suppresses formation of intraductal papillary mucinous neoplasm and pancreatic ductal adenocarcinoma. (PubMed: 24561622)
- Nature (2014) Mouse liver repopulation with hepatocytes generated from human fibroblasts. (PubMed: 24572354)
- Proc Natl Acad Sci U S A (2014) Synthetic control of mammalian-cell motility by engineering chemotaxis to an orthogonal bioinert chemical signal. (PubMed: 24711398)
- Elife (2014) Distinct and separable roles for EZH2 in neurogenic astroglia. (PubMed: 24867641)
- G3 (Bethesda) (2014) Enhancer-trap Flippase Lines for Clonal Analysis in the Drosophila Ovary. (PubMed: 25024257)
- Nature (2014) Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells. (PubMed: 25079315)
- Cell Rep (2014) Control of Outer Radial Glial Stem Cell Mitosis in the Human Brain. (PubMed: 25088420)
- Nat Biotechnol (2014) Low-coverage single-cell mRNA sequencing reveals cellular heterogeneity and activated signaling pathways in developing cerebral cortex. (PubMed: 25086649)
- Nature (2014) Radial glia require PDGFD-PDGFRbeta signalling in human but not mouse neocortex. (PubMed: 25391964)
- J Immunol (2014) Fetal Intervention Increases Maternal T Cell Awareness of the Foreign Conceptus and Can Lead to Immune-Mediated Fetal Demise. (PubMed: 24415782)
- Semin Reprod Med (2013) Human trophoblast progenitors: where do they reside? (PubMed: 23329637)
- Methods Mol Biol (2013) Directed differentiation of human pluripotent stem cells along the pancreatic endocrine lineage. (PubMed: 23546752)
- Nat Commun (2013) Mitotic spindle orientation predicts outer radial glial cell generation in human neocortex. (PubMed: 23575669)
- Cell Stem Cell (2013) Integration of Genome-wide Approaches Identifies lncRNAs of Adult Neural Stem Cells and Their Progeny In Vivo. (PubMed: 23583100)
- Blood (2013) Direct and indirect antigen presentation lead to deletion of donor-specific T cells after in utero hematopoietic cell transplantation in mice. (PubMed: 23610372)
- Cell Rep (2013) Bivalent Chromatin Marks Developmental Regulatory Genes in the Mouse Embryonic Germline In Vivo. (PubMed: 23727241)
- Nature (2013) Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. (PubMed: 23812591)
- Development (2013) A dynamic population of stromal cells contributes to the follicle stem cell niche in the Drosophila ovary. (PubMed: 24131631)
- Dev Biol (2013) Cerebellar Cortical Lamination and Foliation Require Cyclin A2. (PubMed: 24184637)
- J Pediatr Surg (2012) Alterations in maternal-fetal cellular trafficking after fetal surgery. (PubMed: 22703775)
- J Cell Biol (2012) Nodal signaling regulates endodermal cell motility and actin dynamics via Rac1 and Prex1. (PubMed: 22945937)
- PLoS One (2012) The bHLH Repressor Deadpan Regulates the Self-renewal and Specification of Drosophila Larval Neural Stem Cells Independently of Notch. (PubMed: 23056424)
- Clin Perinatol (2012) In utero hematopoietic cell transplantation for the treatment of congenital anomalies. (PubMed: 22682381)
- Chimerism (2012) Maternal microchimerism in patients with biliary atresia: Implications for allograft tolerance. (PubMed: 22772071)