Mike Holmes, PhD, is the Chief Scientific Officer at Ambys Medicines. Holmes is joining the QB3-Berkeley Professionals in Residence (PIR) program on April 16th and 23rd. He spoke with PhD student Diana Aguilar Gómez about his career from being a graduate student to industry. They also discussed his pioneering work in genome editing techniques in gene therapy and the application and importance it has to severe liver disease patients.
Register here to join the PIR events with Mike Holmes on April 16th and 23rd.
Diana Aguilar Gómez: Could you briefly describe your career trajectory?
Mike Holmes: As an undergraduate, I was doing research in a genetics laboratory. I worked very closely with a postdoc who taught me how to work in a lab and do science. I fell in love with doing research. From that point, I decided that was what I wanted to do. I saw myself doing academic research and decided to go to graduate school. I ended up going to UC Berkeley, my first choice. While I really loved doing research, I wanted to do something more applied. I liked the idea of going into industry and trying to build medicines or novel therapies for patients with significant, unmet needs. I became passionate about the idea of applying my research towards building gene therapies and medicines for patients.
DAG: Could you explain what gene therapy is and if genome editing is a type of gene therapy?
MH: Gene therapies very broadly revolve around the idea of delivering genetic payloads to cells. These payloads would change or provide missing factors, to down-regulate or reduce the expression of factors that might be responsible for driving disease. The general sense of gene therapy is the idea of delivering to cells new genetic payloads that would ameliorate the impact of disease. I consider genome editing to be a tool that can be used by gene or cell therapy to invoke a therapeutic response. For example, we might use gene therapy to deliver genome-editing reagents or we might use genome-edited cells to develop better cell therapy.
DAG: What did you do when you finished your PhD at UC Berkeley?
MH: I joined a small company called Sangamo Therapeutics. It was working on how to build engineered transcription factors as a potential gene therapy approach for patients with severe unmet medical needs. Three weeks into my new job, our boss was tragically killed in an accident. We were in a very young company that suddenly didn’t have a clear mentor. Very quickly, many of us within the company found ourselves in leadership roles. With the opportunity I was given out of this tragedy, one of the projects I ended up leading was in genome editing — trying to figure out how to develop genome editing as a way to expand what we could do from a gene therapy standpoint.
DAG: Why did you leave Sangamo Therapeutics to go to Ambys Medicines?
MH: I was at Sangamo for 17 years. I started off as a “scientist one,” and then I left as the Chief Technology Officer. I worked my way up to heading up the research group there. Working with a tremendous group of scientists to invent a field and figure out how to use genome editing in a variety of applications, both for advancing basic science research as well as perfecting it for use as a therapy — it was a dream job for me in terms of just how much success we had and how far we are taking the technology. After 17 years, I found myself wanting to do something kind of new and different. The company had grown to 300 people. Oftentimes, I was in a variety of meetings that had nothing to do with science; it had to do with running a larger company. I wasn’t passionate about the nuts and bolts of running a large company, and I want to get back to my roots.
I moved to a startup company called Ambys Medicines in 2018. This company has the mission of trying to find novel therapies for patients with severe liver disease. For patients with both acute and chronic liver disease where the disease is so severe, the standard of care for them is one of liver transplant. There are probably more than 30,000 people in the United States who are in need of significant therapy for liver disease, but we only do about 8,500 transplants per year. The number of patients is expected to actually grow over the next decades, and therefore, there is a significant amount of unmet need.
DAG: How are you tackling this problem at Ambys Medicines?
MH: We are using cell and gene therapy to try and regenerate the liver in patients with severe liver disease. From a gene therapy perspective, the idea is in the context of cirrhosis, when the liver is no longer able to regenerate itself to maintain sufficient liver activity and function. In the context of gene therapy, can we deliver genes that can modulate the different pathways that are involved in driving severe liver disease and cirrhosis? We want to stop and potentially reverse the changes that have occurred in the liver. Our aim is to restore the natural regenerative processes in the liver. In the context of cell therapy, what we’re doing is we’re getting primary human hepatocytes, and we’re expanding them outside the body. We can introduce them back into patients, such that we can augment liver function, ameliorate disease, and significantly improve the quality of patients’ lives. Those are the two scientific pillars of Ambys. To replace the need for transplants is our big mission.
DAG: What does a typical day look like for you?
MH: Right now, in the context of COVID-19, I spend a lot of time in meetings over Zoom, staying in touch with people and having meetings to talk about the science that we’re doing and to discuss next steps. We are essential. We do have many of the people here on site. However, it’s one of the things where, in science, sometimes some of the best discoveries or best discussions are you just going down the hall, seeing the person, and working on the whiteboard. Zoom has helped us a lot in terms of staying in touch, but that’s the one thing that we haven’t found a technology for to replace those one-on-one informal discussions that a lot of times discoveries come out of.
DAG: Do you have any advice for PhD students who are considering going to industry?
MH: Think about the scientific problems facing society, and the topics that you’re really passionate about. Find the job and the company that best matches up with that passion. Science is tough; it’s challenging, many experiments just don’t work. You need to work in a field that is exciting for you. One of the things that drew me to industry was the tangible applications like a project becoming a drug or treatment for disease.
DAG: Why did you decide to take part in this program with UC Berkeley?
MH: I greatly appreciate all the opportunities that UC Berkeley gave me, both in terms of the education and the connections I made. I certainly greatly appreciate the experience I had in getting me ready to build my career. I like the idea of giving back to Berkeley and do anything I can do to help the students and the people. In learning from my own experience, how can I better help them in making the right choice? I remember being at the same stage and trying to figure out what I wanted to do. I remember going to a variety of very similar presentations — people talking about going into consulting or industry. I appreciate these different perspectives. If I can participate in this and help even one person, then I think it’s worthwhile and paying back to all those before me who helped me.
Mike Holmes, PhD, is a passionate scientist who is currently Chief Scientific Officer at Ambys Medicine. He gained his PhD in molecular and cell biology from UC Berkeley. After he graduated and did a short postdoctoral training, Mike transitioned to industry. He worked 17 years for Sangamo Therapeutics, where he and a group of talented scientists were pioneers in developing gene therapies involving genome editing tools. Mike received his BS in molecular biology from UC San Diego.
Diana Aguilar Gómez is a PhD Candidate in the Computational Biology program which is affiliated with QB3-Berkeley. She is working on her thesis at the Nielsen lab and her research involves population genetics and evolution of coloration in lizards and frogs.