Tan Ieng Huang came to the U.S. from China for high school and is a SPARK student at CIRM. During her internship at UC San Francisco, she worked in Dr. Arnold Kriegstein’s lab. He is the founding director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF. Not only did Tan Ieng work in his lab—but she also interviewed him about his research and views on the field.

This fascinating interview showcases our SPARK students’ creativity and curiosity. You’ll see more examples of that creativity in the coming weeks. For now, enjoy her conversation with a major force in the field today—and who may soon have company from bright young scientists like her.

‘a tête-à-tête with Prof. Arnold Kriegstein’

Prof. Arnold Kriegstein is the Founding Director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UC San Francisco. He also serves as the co‑founder and scientific advisor of Neurona Therapeutics. Neurona aims to develop safe, effective cell therapies for chronic brain disorders.

Trained as a clinician, Prof. Kriegstein has long been fascinated by the human brain. His lab studies the transcriptional and signaling networks that guide brain development. They also examine the diversity of neuronal cell types and their potential fates. He has worked for years to apply this knowledge to therapeutic development.During my SEP internship, I had the chance to work in the Kriegstein lab. I was in awe. I’m fascinated by the brain, and over two months, I interacted with Prof. Kriegstein often. His insights were remarkable. Here are some excerpts from our conversations to inspire others, too.

Can you share a little bit about your career journey as a scientist?

Prof. Arnold Kriegstein (AK): I wanted to be a doctor from a very young age. In high school, I began doing hands‑on research and discovered that I loved working in the lab. From then on, I looked for a way to combine those interests, and an MD/PhD became the ideal path for me.

I later became interested in the nervous system. In high school, I spent a summer at Rockefeller University studying operant conditioning in rodents. That experience sparked my fascination with behavior and the brain’s role in learning and memory. Those early interests grew into a focus on cortical development and, over time, shaped my career.

What inspired you growing up, and what made you choose medicine as a career?

AK: It’s a little hard to say what drew me to medicine because I have an identical twin brother. We always shared activities and did things together. Early on, we even became Eagle Scouts. To earn that rank, we applied to a special program that let us shadow physicians at a local hospital. I remember doing that when I was very young.

One evening, they showed us films of eye surgery. My brother fainted when the surgeon made an incision in the eye. It’s funny to me now because he became an eye surgeon many years later.

That early experience stayed with us. We both became fascinated by medicine and medical research.

What inspired you to start the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research Institute?

AK: My interest in brain development over the years became focused on earlier stages of development and eventually Neurogenesis, you know, how neurons are actually generated during early stages of in utero brain development.

In the course of that, we discovered that radial glial cells, long thought to simply guide migrating neurons, were actually neural stem cells. They made neurons and also guided them toward the cortex. So they were these master cells, hugely important, now referred to as neural stem cells.

But at that time, it was really before the stem cell field took off. Because we studied neurogenesis, and because I contributed to understanding how the brain develops, it was easy for me to identify as someone who studied neural stem cells. I became a neural stem cell scientist. When I was a professor at Columbia University, I started a neural stem cell program, raising $ 15 million to seed it. Shortly after, I was approached to join UCSF as the founder of a new stem cell program. It was much broader than the nervous system; it covered all the different tissues and organ systems.

Can you tell us a little bit about how stem cell research is contributing to the treatment of diseases? How far along are we in terms of treatments?

AK: It’s taken decades, but things are really starting to reach the clinic now. The original work was basic discovery in research laboratories. Now it’s moving toward the clinic. It’s a really exciting time. Initially, the promise of stem cell science was called Regenerative medicine. The idea is to replace injured or worn-out tissues or structures with new cells, new tissues, and new organs. Regeneration became possible by understanding that stem cells can be tweaked to help make new cells and tissues.

It’s a very exciting process, but the main progress so far hasn’t been replacing worn-out tissues and injured cells; it’s been understanding diseases using a human-based model. That’s largely because of the advent of induced pluripotent stem cells, a way to make neurons, heart cells, or liver cells in the laboratory and study them both under normal developmental conditions and in disease states. Those platforms, which are relatively easy to make now and are pretty common all over the world, allow us to study human cells rather than animal cells, and the hope is that by doing that we will be able to produce conventional drugs and treatments that work much better than those we had in the past, because they will be tested in actual human cells rather than animal cells.

There are still many species-specific differences, right?

AK: Absolutely, in fact, one of the big problems now in Big Pharma, you know, the drug companies, is that they invest millions and sometimes hundreds of millions of dollars in research programs that are based on successes in treating mice, but patients don’t respond the same way. So the hope is that starting with a treatment that works on human cells makes it more likely to work in human patients.

What are your thoughts on the current challenges and future of stem cell research?

AK: I think this is an absolute revolution in modern medicine. The advent of two things that are happening right now: first, the use of induced pluripotent stem cells- the ability to make pluripotent cells from adult tissue or cells from an individual allows us to use models of diseases that I mentioned earlier from actual patients. That’s one major advance. And the other is gene editing, and the combination of gene editing and cell-based discovery science allows us to think of engineering cells in ways that can make them much more effective as a form of cell therapy, and those cell therapies have enormous promise. Right now, they are being used to treat cancer, but in the future, they might be able to treat heart attack, dementia, neurodegenerative diseases, ALS, Parkinson’s disease, a huge list of disorders that are untreatable right now or incurable. They might be approached by the combination of cell-based models, cell therapies, and gene editing.

What are the challenges now?

AK: You know, like many other technologies, there are uncertainties, and there are some issues. Some problems are off-target effects: you try to change one particular gene, but you might also change other genes in unexpected ways and cause complications. But we understand this better now and can make much more precise gene-editing changes in individual genes without affecting unanticipated areas of the genome. And then there are also the problems of how to gene-edit cells in a safe way. Certain viral factors can introduce the gene-editing apparatus into a cell, and if you are doing that in a patient, you can also get unwanted side effects from the vectors you use; often, these are modified viral vectors. So things get complicated very quickly when you start trying to treat patients, but I think these are all tractable problems, and I think they will all be solved over time. It will be a terrific, very promising future for treating patients who are currently untreatable.

Do you have any advice for students who want to get into this field?

AK: Yes, I think it’s never been a better time. I’m amazed by the technologies available now. Gene editing, as I mentioned, and single‑cell approaches—including single‑cell multi‑omics—let us study gene expression in individual cells and understand how cells form, change, and shift into new fates. These tools allow us to envision true regenerative medicine: healing or replacing injured or diseased tissues. I think this is becoming possible now, making it an incredibly exciting time. Anyone interested in stem cell biology or new ways to treat disease should get into a lab or clinical setting. This moment is more exciting than ever.

What motivates you every day to do Research and contribute to this field?

AK: Being an MD/PhD means working with two different reward systems. On the PhD side, discovery drives him. I enter the lab each day knowing I might learn something no one has seen before. Those moments feel incredibly satisfying.

On the MD side, helping patients has always motivated me. I planned to become a neurologist and treat adults and children with neurological disorders. Over the past decade, I spent less time with patients and more time in the lab. Still, my team has begun moving discoveries into the clinic. They recently launched a clinical trial of a new cell‑based therapy for epilepsy at Neurona Therapeutics, which I find very exciting.

I hope the therapy helps patients. It also gives him the rare chance to watch a lab project grow into a potential treatment. This brings together his two passions: basic science and clinical medicine. I feel a little late in life, but not too late, and I am very excited about it.

Tan Ieng Huang, Kriegstein Lab, SEP Intern, CIRM Spark Program 2022