UCLA scientists receive CIRM grants to advance stem cell-based treatments for vision loss and infertility, and improve CAR T-cell therapy

Scientists at the UCLA Broad Stem Cell Research Center have received $7.4 million in grants from the California Institute for Regenerative Medicine, the state’s stem cell agency, to advance new stem cell-based treatments for irreversible vision loss and infertility and investigate the factors that determine why CAR T-cell therapies work for some patients and not others.

Mapping retinal environments to improve regenerative therapies for vision loss

Dr. Aya Barzelay-Wollman, assistant professor of ophthalmology

Millions of people with geographic atrophy — an advanced, late-stage form of dry age-related macular degeneration — experience progressive, irreversible vision loss, and no existing treatment can restore retinal tissue that has been lost to this disease. Stem cell-based approaches offer the possibility of replacing damaged retinal cells, but the survival of transplanted cells can be unpredictable in diseased tissue.

Barzelay-Wollman’s $2.5 million award will support her laboratory’s work to understand why. Her research will focus on the transition zone — the irregular boundary between surviving retina and areas of complete atrophy, where some of the last viable retinal cells are found. By studying this critical region in human tissue, her team aims to identify the biological conditions that determine whether transplanted retinal cells survive and integrate or fail.

Using human donor tissue, stem cell-derived retinal cells and advanced molecular analyses, Barzelay-Wollman and her team will map the cellular, molecular and structural features of distinct retinal environments and test how transplanted cells respond within them. The findings could reveal which local conditions help or hinder transplanted-cell survival and whether those barriers can be modified, providing a foundation for more effective regenerative therapies for geographic atrophy. 

The project also includes a collaboration with Dr. Tsu-Chin “T-C.” Tsao, distinguished professor of mechanical and aerospace engineering at UCLA, who will contribute engineering expertise to a component of the study involving precision robotics.

A physician-scientist, Barzelay-Wollman treats patients with retina diseases at the UCLA Doris Stein Eye Research Center and is a former clinical fellow in the Broad Stem Cell Research Center Training Program.

Mapping how human germ cells form to advance infertility treatment

Dr. Amander Clark, professor of molecular, cell and developmental biology

Infertility affects about one in six people of reproductive age, yet many cases remain unexplained. Some may originate very early in embryonic development, when primordial germ cells — the cells that eventually give rise to eggs and sperm — first form.

Clark is a co-investigator on a collaborative project led by Dr. Magdalena Zernicka-Goetz, professor of biology and biological engineering at the California Institute of Technology. Their $2.4 million award will support efforts to understand the surrounding tissues and signals that guide primordial germ cells as they emerge.

Using two complementary stem cell-derived models of early human development, their teams will map where and when primordial germ cells arise, identify the neighboring tissues that guide them and determine which molecular signals are essential for their development.

By creating a more detailed blueprint of this process, the researchers hope to uncover early mechanisms that contribute to infertility and help scientists more accurately recreate human germ cell development in the lab, laying a foundation for future approaches to diagnosis and treatment.

Clark is the inaugural director of the UCLA Center for Reproductive Science, Health and Education.

Uncovering why CAR T-cell responses succeed or fail in cancer and autoimmune diseases

Dr. Dino Di Carlo, Armond and Elena Hairapetian Professor and Chair of Bioengineering

CAR T-cell products that meet the same quality standards can perform well in some patients but fail in others. Understanding what drives those differences is increasingly important as CAR T-cell therapies expand beyond cancer into autoimmune and neuro-immune diseases such as lupus and multiple sclerosis.

Di Carlo is a co-investigator on a collaborative project led by Dr. Mohamed Abou-el-Enein, associate professor of clinical medicine in oncology, pediatrics, and stem cell biology and regenerative medicine at the Keck School of Medicine of USC. Their $2.49 million award will support efforts to uncover the cellular mechanisms that distinguish productive CAR T-cell responses from those that become dysfunctional.The researchers will investigate how factors including the starting state of a patient’s immune cells, the genetic elements controlling CAR expression and patterns of antigen exposure influence CAR T-cell function. 

Abou-el-Enein’s laboratory will use high-dimensional flow cytometry and computational analysis to build a detailed atlas of CAR T-cell states across patients and diseases. Di Carlo’s laboratory will leverage its nanovial technology and Cell-Cell-seq approach to study individual CAR T cells as they interact with their targets, linking whether a target cell is killed and other functional responses with the gene expression patterns in both cells. By integrating these interaction-level insights with the broader cellular atlas, the team aims to identify molecular and cellular patterns associated with effective CAR T-cell responses and dysfunction.

This resource could help identify more informative measures of therapeutic potency and guide the development of more consistent and durable cell therapies across patients and diseases.