Pioneering Regenerative Medicine: Research at the UCLA Broad Stem Cell Research Center

The UCLA Broad Stem Cell Research Center (BSCRC) stands at the forefront of regenerative medicine, driving innovation and translating groundbreaking stem cell research from the laboratory to the patient's bedside. Rooted in the ambition of translating novel discoveries into tangible therapies, the BSCRC fosters a collaborative and technologically advanced environment that accelerates the clinical translation process.

Mission and Approach

BSCRC's mission revolves around supporting innovation, upholding the highest ethical standards, and accelerating the transition of groundbreaking stem cell research from the laboratory to the patient. The center transcends traditional academic boundaries, promoting technology-driven, cross-disciplinary research spanning fundamental discoveries to clinical applications. With over 250 faculty members representing diverse departments, schools, and disciplines, the BSCRC embodies the belief that stem cell research thrives in a truly interdisciplinary environment.

History and Development

Established in 2005 as the Institute for Stem Cell Biology and Medicine by then-UCLA Chancellor Albert Carnesale, the center was created to foster multidisciplinary teams of UCLA stem cell researchers. These teams would leverage cutting-edge technologies to pave the way for the next generation of medicine. Under the guidance of founding director Owen Witte and co-director Judith Gasson, the institute initiated the recruitment of internationally renowned scientists. The BSCRC also prioritizes education, offering training programs for UCLA undergraduate and graduate students, postdoctoral scholars, and clinical fellows, as well as undergraduates from California State University, Northridge, through a dedicated partnership.

Cancer and Stem Cell Biology Research Program (CSCB)

The Cancer and Stem Cell Biology Research Program (CSCB) bridges basic and translational investigators who share an interest in the unique biological processes of malignancy and stem cells. A deeper understanding of how normal and aberrant cells self-renew and differentiate is expected to provide novel biological insights into the initiation, progression, and recurrence of cancer. This knowledge empowers researchers to explore novel therapeutic targets and biomarkers.

CSCB members are drawn from three UCLA schools and affiliated institution Caltech. While each CSCB investigator typically focuses on either hematopoietic or epithelial stem cells, the shared biology of stem cells and cancer across all tissue types has cultivated a highly interactive environment within the CSCB research program. This collaboration is further strengthened by the close relationship between the UCLA Health Jonsson Comprehensive Cancer Center and the UCLA Broad Stem Cell Research Center. Nearly every CSCB investigator is involved in at least two of the program's specific aims, utilizing animal model systems, human pluripotent stem cells, and primary human tissues to uncover basic biologic processes and reveal new opportunities for cancer treatment.

Specific Aims of the CSCB Research Program

The primary objective of the CSCB research program is to connect basic and translational investigators interested in the shared biological processes of malignancy (de-differentiation) and stem/progenitor cells. Specific aims of the research program are:

To understand how the biology of epithelial and mesenchymal stem cells is regulated during malignant transformation and normal development.
To define the mechanisms that regulate growth and differentiation of Hematopoietic Stem and Progenitor Cells (HSPCs) during malignant transformation, normal development, aging, and after transplantation.
To determine the role of the microenvironment in tumor formation and stem cell regulation.

CSCB Leadership

Dr. Gay Crooks, the Rebecca Smith Professor of Pathology and Laboratory Medicine and Pediatrics at UCLA, directs the CSCB research program. Dr. Crooks, who became director in 2015 after serving as co-director for three years, is also the co-director of the UCLA Broad Stem Cell Research Center. Her research interests encompass human hematopoiesis from adult human hematopoietic stem cells and pluripotent stem cells, T lymphoid differentiation from stem cells, and microenvironmental control of hematopoiesis. Dr. Brigitte Gomperts, Full Professor of Pediatrics and Pulmonary Medicine and Vice Chair for Research in the Division of Pediatric Hematology-Oncology, joined Crooks as co-director of CSCB in 2015. Dr. Gomperts' research focuses on airway epithelial homeostasis and lung carcinogenesis, as well as the role of the microenvironment in regulating airway repair after injury.

Clinical Trials: A Phased Approach to New Therapies

All research conducted at the BSCRC is driven by the ultimate goal of bringing new therapies to patients. Potential therapies undergo rigorous testing in a stepwise manner to evaluate their safety and effectiveness. This process begins in the lab, progresses to preclinical models, and culminates in a series of clinical trials.

Clinical trials are research studies that involve people. They are essential for determining if a new medical strategy, treatment, or device is safe and effective. These trials are carefully designed and monitored to protect the participants and ensure the integrity of the data.

The clinical trial process is typically divided into phases, each with a specific purpose:

Read also: Navigating Tech Breadth at UCLA

Phase I: Evaluating Safety and Dosage

Phase I clinical trials primarily focus on evaluating the safety, dosage range, and potential side effects of a therapy in a small group of humans. Traditionally, these trials are conducted in healthy volunteers. However, due to the unique characteristics and potential risks associated with cell and gene therapies, Phase I trials at the BSCRC are often conducted in individuals who have the disease or condition the therapy is intended to treat. This approach allows researchers to gather relevant safety and efficacy data in a more representative context before moving on to later-phase trials.

A critical aspect of Phase I trials is monitoring for adverse events, which are any unexpected health problems that might occur. If a study isn't deemed safe, it won't move on to the next phase.

Phase II: Assessing Efficacy and Side Effects

After safety has been assessed in a limited number of subjects, Phase II trials evaluate a treatment's efficacy and side effects in a larger group of patients. These trials typically involve a few hundred participants and are designed to help determine the optimal dosage and identify common short-term side effects. The key questions addressed in Phase II are: Is it safe to continue testing, and does it work?

Phase III: Confirming Effectiveness in a Broader Population

To confirm a treatment's effectiveness, monitor side effects, and compare it to standard treatments or a placebo, researchers conduct Phase III trials with a significantly larger number of participants, often ranging from several hundred to several thousand. This phase provides essential data for regulatory approval and is pivotal in shaping the drug's labeling and usage instructions.

Phase IV: Monitoring Long-Term Benefits and Risks

Even after a treatment has been approved and marketed to the public, Phase IV trials continue to monitor its long-term safety and effectiveness. This ongoing surveillance helps identify any rare or delayed side effects and provides a more comprehensive understanding of the treatment's overall benefit-risk profile.

Read also: Understanding UCLA Counselors

Advanced Capabilities and Resources

In 2021, UCLA established the Dr. Allen and Charlotte Ginsburg Center for Precision Genomic Medicine, which includes the UCLA Stem Cell and Genome Engineering Center (HSCGEC). The HSCGEC serves as a central hub for stem cell and genome engineering efforts within UCLA and the West Coast.

The HSCGEC offers cutting-edge services focused on:

Generating pluripotent stem cells from patient samples.
Providing genome engineering and editing services for basic core and preclinical research.
Conducting chemical and CRISPR screenings, including CRISPR-mediated activation and/or inhibition of genes.

Beyond its core functions, the center also engages in independent research, optimizing published techniques to ensure reliable and reproducible methodology, and pioneering novel differentiation paradigms. The HSCGEC maintains and provides well-characterized human embryonic stem (hES) cell lines and human induced pluripotent stem (iPS) cell lines. The Center Director and staff offer consultation on experimental design and can assist in getting projects involving pluripotent cells moving quickly.

Recent Advances and Ongoing Research

The BSCRC is actively involved in a wide range of research projects, including:

Gene Therapy for Immune Diseases: BSCRC scientists have initiated cell and gene therapy clinical trials for patients with deadly immune diseases. For example, BSCRC researchers have made significant strides in lentiviral gene therapy for X-linked chronic granulomatous disease and autologous ex vivo lentiviral gene therapy for adenosine deaminase deficiency.
Immunotherapies for Cancer: UCLA has a history of success in developing novel immunotherapies to treat cancer.
Stem Cell Therapies for Eye Diseases: BSCRC researchers are exploring stem cell-based therapies for blinding eye diseases. Recent studies have focused on the safety and feasibility of cultivated autologous limbal stem cells (cLSC) for limbal stem cell deficiency.
Induced Pluripotent Stem Cells (iPSCs): BSCRC researchers have made significant contributions to the development and application of iPSCs, including the generation of human iPSCs from dermal fibroblasts.

Meetings and Seminars

The BSCRC actively fosters collaboration and knowledge sharing through a variety of meetings and seminars, including:

Participation in the UCLA Health Jonsson Comprehensive Cancer Center seminar series.
Sponsorship of the Cell and Developmental Biology weekly seminar series.
Co-sponsorship of the annual UCLA Stem Cell Symposium.
Co-sponsorship of the monthly Hematology Research Meeting âBlood Groupâ with the ERGR Research Program.
Sponsorship of outside invited speakers that focus on research related to cancer and stem cell biology.
Monthly seminars for Pre-doctoral and Postdoctoral students supported on T32 grants associated with the program (Tumor Cell Biology, Vascular Biology, CIRM training grants).

tags: #UCLA #stem #cell #institute #research