January 2025

At the January faculty meeting, the Institute for Stem Cell Biology and Regenerative Medicine  formally welcomed four new members. The researchers being welcomed to the institute come from a variety of stem cell-related fields: early human development, immune system gene therapy, liver function and regeneration, and stem cell interactions in primitive marine creatures. ISCBRM Director Ravi Majeti said “We are thrilled to expand our membership to include such amazing scientists working across basic and translational domains. All four of these faculty are world leaders in their disciplines and bring new opportunities for mentorship and collaboration with the ISCBRM community.”

Lay Teng Ang, PhD

Originally from Singapore, Ang earned her PhD from Cambridge University, then returned to her home city to become a Research Fellow at the Genome Institute of Singapore. In 2018, she moved to Stanford as Instructor and Siebel Investigator in the Institute for Stem Cell Biology and Regenerative Medicine. Recently, she was appointed as Assistant Professor in the Department of Urology.

Much of Ang’s research has been focused on pluripotent stem cells and how they can be guided to differentiate into pure populations of particular cell types. Currently, most differentiation schemes result in mixed populations of cell types that are of limited use in research or in the clinic.

Collaborating with other institute colleagues over the years, she has mapped out the successive binary choices, and the agents that influence those choices, that define the path from pluripotent stem cell to very pure populations of human heart and vascular endothelial cells. Currently, she studies the branching lineage choices, signals, and mechanisms that lead cells from a pluripotent state into functional blood vessels (e.g., endothelial cells, smooth muscle cells, fibroblasts) and functional epithelial cells (e.g., bladder and liver cells). 

“There are many patients with liver failure on the transplant waiting lists, and many of them will not be able to get a new liver,” Ang said. “If you could create a batch of very pure liver stem cells, you might be able to use stem cell therapy to help people regenerate their own livers. Liver cells could also be used to study the efficacy and toxicity of new drugs,” she said.

In the future, Ang is interested in generating bladder epithelial cells, making pure populations of more mature liver cells, and being able to make all three layers of blood vessels directly from pluripotent cells.

Becoming an institute member is meaningful to Ang. She said. “I look forward to continuing to work with other faculty and with students to advance the work taking place in my lab,” she said. “The institute has such an amazing cast of faculty members, it is so empowering to work with them.”

Rosa Bacchetta, MD

Rosa Bacchetta is well known to many in the institute. She has been at Stanford since she arrived as a visiting scientist in 2012. In 2014, she started working with the then institute co-director Maria Grazia Roncarolo, and in 2015 she became an Associate Professor of Pediatrics, in the Division of Stem Cell Transplantation.

“I’m really happy to become a member of the institute, not only because I really love the work being done here, and because there are really so many relationships between the work I do with T cells and the process of tissue regeneration and repair,” Bacchetta said.

Bacchetta arrived at Stanford with an expertise in IPEX syndrome, a genetic autoimmune disease, although the clinical application of her work has become relevant to many autoimmune diseases. “For serious early-onset autoimmune diseases, gene therapy offers the best possible cures” she said.

Although some of her work involves genetically engineered stem cells, the work that has progressed farthest is with engineered regulatory T cells, or Treg cells. Because Treg cells modulate the body’s immune responses, engineered Treg cells can be a critical lever for controlling IPEX. “The project has grown immensely over the years,” Bacchetta said. “We get emails from people all over the world with this rare disease.”

Bacchetta and her colleagues are currently running a phase one clinical trial of engineered autologous Treg cells, treating six patients and testing the treatment for signs of toxicity.

Although IPEX is a rare disease, the strategy of using engineering Treg cells could potentially be used to treat much more common autoimmune disorders like lupus or rheumatoid arthritis. “Treg therapy is very hot area, it’s very promising,” Bacchetta said. “Stanford is becoming a worldwide center for IPEX and immune dysregulation diseases.”

Matteo Molè, PhD

Originally from Italy, Matteo Molè came to Stanford 1 year ago from a position at Cambridge University in the UK. He is an Assistant Professor in the Department of Obstetrics and Gynecology in the Stanford School of Medicine. Molè studies implantation of the human embryo when it attaches to uterine tissue and begins to form the placenta.

“There are several reasons for studying this,” Molè says. “For one thing, we know very little about this process, because it happens inside the uterus and is inaccessible. We only have a few specimens, only three microscope sections, showing this happening.”

“The other reason is the clinical importance of information about this process,” he says. “Successful implantation is the limiting factor in IVF. Up to 60% of embryo transfers fail to implant.”

Implantation also may hold important lessons about the immune system and the vascular system, Molè says. “The implanted embryo has to work to not be rejected by the immune system, and also has to create a placenta that perforates the maternal vascular system and acts as a conduit for nutrients and messaging molecules.”

Molè was drawn to Stanford because it has a strong clinical Ob/Gyn department and a culture of cooperation between clinical and basic research. “Stanford is a good collaborative environment, where scientists can learn from clinicians, go back to the lab to advance our understanding, and then bring that knowledge back to clinicians to improve care,” he said. He was also attracted by funding available from CIRM and the presence of the Renew BioBank, which makes studying human embryos easier. “Embryos are so beautiful,” Molè said. “I am very happy spending hours and hours looking at them.

Ayelet Voskoboynik, PhD

Ayelet Voskoboynik has the privilege of studying one of the world’s strangest organisms in one of the most beautiful places on earth. Most of the week, Voskoboynik is in her lab at the Hopkins Marine Station in Monterey studying Botryllus schlosseri, a sea creature that is actually a colony of individual clones sharing a common circulatory system. It is our closest marine invertebrate relative.

Every week, each Botryllus organism in a colony reproduces asexually, producing 2-4 buds that become new organisms. Each bud completes its development within two weeks, lives as an adult for one week, and then deteriorates and dies on the last day of the third week. Voskoboynik studied Botryllus’ cellular deterioration while a graduate student in Israel and discovered that treating the colonies with antioxidants halted the programmed cell death in the colonies. Irv Weissman predicted that she was doing something to the colony’s stem cells and invited her to Stanford to continue research along these lines. “Of course he was right,” Voskoboynik said. “Irv is always right about stem cells.”

Over the years, Voskoboynik’s lab made major strides in studying this unusual organism. In 2013, Voskoboynik and her colleagues sequenced the Botryllus genome, creating a map that can guide myriad new studies into Botryllus’ biology. To accomplish this feat, Voskoboynik, Steve Quake, Irv and their colleagues developed new techniques for sequencing whole genomes, techniques that are still in use today.

With a full genome in hand, Voskoboynik and her group were able to isolate BHF, a factor that determined whether cells from other organisms in the same colony were treated as “self” or “non-self,” and thereby rejected or accepted. Voskoboynik is now working with other Stanford scientists to understand how this gene works to accomplish this differentiation.

During one phase of its life, Botryllus reproduces asexually, but in another phase it reproduces sexually. The group compiled a microscopic atlas of Botryllus anatomy in these two phases of life. This atlas and the Botryllus genome also allowed Voskoboynik to study the differences in the genetic program between the two modes of reproduction and development. These studies reveal new insights into how reproduction and regeneration work in all animals.

Another branch of the Voskoboynik Lab studies of Botryllus focuses on the generation and regeneration of the Botryllus nervous system. This work has the potential to offer insights into neurodegenerative disorders across all species.

A year ago, Voskoboynik became an Assistant Professor in the Department of Biology and is now looking forward to continuing her work as a member of the institute. “I feel like the institute has already been my home for so long now,” Voskoboynik said. “I’m looking forward to extending and deepening that relationship as a member.”