NIBR's new Neuroscience team will leverage the latest advances in human genetics to probe the underlying pathophysiology of neuropsychiatric and neurodegenerative diseases. NIBR hopes to hire 30 associates by the end of 2013 and 70 more over the next three years. The goal is to harness the recent explosion of neuroscience knowledge and technology to help patients.
Ricardo Dolmetsch was living the scientific dream by his mid thirties. Already a professor at Stanford, he was running a successful lab, winning grants and receiving recognition for work on calcium channel signaling. But then his son was diagnosed with autism.
Determined to understand—and perhaps even treat—the disease, Dolmetsch redirected his entire lab, pivoting from esoteric biophysics experiments to research with clear, immediate connections to neurodevelopmental disorders. Having a mission changed everything.
"I basically gave up all my grants and applied for new ones in 2007,” says Dolmetsch, who recently became Global Head of Neuroscience at NIBR. “The transition that year was very traumatic and painful from a professional perspective, but it was great from a personal perspective."
Dolmetsch assembled talent and acquired new skills to explore the molecular roots of his son’s condition. He became an expert on induced pluripotent stem cells, for example, which enabled him to develop an in vitro model of Timothy syndrome, a rare disease with a variety of symptoms, including the characteristic features of autism.
Timothy syndrome provided a springboard for his larger quest. And knowledge of calcium channels came in handy because they’re mutated in patients with the disease, a discovery made only recently, after Dolmetsch had spent more than a decade studying their basic biology. Dolmetsch also advanced his research agenda as senior director of molecular networks for the Allen Institute for Brain Science.
His unconventional professional journey continues at NIBR, where he plans to pursue therapies for autism, schizophrenia, and other diseases through his global leadership role. According to Dolmetsch, the field is finally ripe for rational drug discovery, so now is the perfect time for the company to re-launch its neuroscience program. And he’s ready to lead the charge.
The Neuroscience team will leverage the latest advances in human genetics to probe the underlying pathophysiology of neuropsychiatric and neurodegenerative diseases. They’ll also take advantage of new tools, including induced pluripotent stem cells, to build disease models and manipulate neural circuits. Dolmetsch hopes to hire 30 associates by the end of 2013 and 70 more over the next three years. The goal is to harness the recent explosion of neuroscience knowledge and technology to help patients.
The group will also build on successes within NIBR. Neuroscience has a long history at Novartis, which manufactures Ritalin and Exelon Patch.
"I’ve spent a lot of time working to understand autism and other diseases because I really care about the people affected, but at some point you have to start doing something to help them instead of just concentrating on the pure biology," says Dolmetsch.
He’s now positioned to make a difference in many lives. It’s a wonderful—and surprising—place to be, says Dolmetsch. A career in science seemed beyond the realm of possibility when he was growing up in Cali, Colombia. Following is an excerpt from a conversation with Dolmetsch about his path to NIBR and vision for neuroscience.
Did you know from a young age that you wanted to be a scientist?
RD: I come from a family of artists. My mother is an eccentric human rights lawyer; my dad is a musician. They wanted me to be Bohemian and play the guitar, and, in fact, they were heartbroken when I told them I was going to become a scientist. But research wasn’t something I thought about as a young kid.
When did that change?
RD: I was an undisciplined kid, and I went to this nice, but slightly rigid school, where I was a good student with lots of attitude problems. I was suspended for two weeks when a nun caught me typing dirty limericks, so I had to find something to do at home. I discovered that my sister had all of these bread-making books and decided to test them out. It turns out I’m really good at following directions. I also tried altering the recipes, systematically changing the quantities and ingredients, which was really fun. It occurred to me that scientists do these types of experiments all the time.
What did your lab study at Stanford?
RD: Before 2007, we studied something really basic: ion channel signaling, which is ultimately important for understanding how experience changes the development and function of the brain. The lab was actually quite successful, but then the focus changed when my son was diagnosed with autism.
How did your perspective shift after the diagnosis?
RD: I was very worried, so I spent a lot of my time poring over the scientific literature to learn as much as possible about autism. I eventually thought—if I’m going to spend all this time figuring out what is known about this disease, then I might as well work on it in the lab. There’s nothing like having a mission to focus your resources.
Which questions did you tackle first?
RD: Idiopathic autism is a really tough thing to work on because it’s not a single disease; it’s a whole bunch of different diseases. I realized that it was going to be difficult to get any traction on something that was so diverse, so I decided to focus on a few orphan diseases related to autism, including Timothy syndrome. Orphan diseases are often easier to characterize on a mechanistic level, and they can provide clues about the molecular underpinnings of more common diseases.
Why did you leave Stanford for industry?
RD: Over the past few years, I’ve gotten to know a lot of kids with autism and other neurodevelopmental diseases, and I’ve become really committed to their welfare. I think that we now have an opportunity to develop therapies for some of them, which is exciting. This is a very special time for neuroscience. The field is finally ripe for rational drug discovery.
What’s happened to enable rational drug discovery?
RD: We’ve recently obtained genetic clues about the underlying pathophysiology of many neuropsychiatric and neurodegenerative diseases. And we have some new tools that make the preclinical work more feasible. For example, induced pluripotent stem (iPS) cells allow us to grow neurons derived from patients’ skin or blood cells. In oncology, scientists have long been able to take biopsies from patients’ tumors, culture those cancer cells and build models, which can be used to develop treatments. Neuroscientists can’t take biopsies from patients’ brains, but iPS cells offer a way around this hurdle.
RD: I was attracted to the academic culture of NIBR. If you’re trained as a biologist, you care about two things: conceptual advances and making people’s lives better. Here we can do both.
Who’s your favorite scientist and why?
RD: Max Perutz. He was the leader of the Laboratory of Molecular Biology (LMB) at Cambridge at the time that Watson and Crick and Sanger were there. Over the course of about 10 years, the LMB group won something like five Nobel Prizes. I think Perutz was a great leader. Based on everything I’ve read, he believed in soft power. His goal was to create an environment for really smart people to do really well, and he pruned things so that they grew into the right shape without imposing too many constraints from the top.