Overview of my current research program and what I pitched at Yale Lifesciences PitchFest:
Alzheimer’s diseases is a devastating neurodegenerative condition for which there is essentially no treatment. There are many potential reasons for the lack of treatment including a poor understanding of what triggers the disease, mechanisms of progression and potential targets for therapy. For the past several decades there has been more interest in the accumulation of deposits of amyloid in the brain as potential targets. However, recent trials with anti-amyloid antibodies have demonstrated that at best this strategy is going to be marginally successful and it carries significant potential side effects. Our focus has been on the downstream pathological impact of amyloid deposits. We have shown that each amyloid plaque in the brain can affect up to a 1000 axons by inducing the formation of large spheroids (swellings) that disrupt the electrical axonal conduction as they enlarge. We have been studying the cell biology and signals that induce the formation of these spheroids and that mediate their enlargement. We have also identified potential molecular targets and have demonstrated that through gene therapy and other approaches we can diminish the formation of spheroids and reduce their enlargement. It is important to note that these treatments were associated with marked improvement in the electrical conduction of axons. Given the critical importance of efficient long-range signaling through axons between the different brain areas for critical functions such as memory, we believe our strategy is a novel approach that targets neurons directly, and we hope it will ultimately be beneficial for patients. With Blavatnik funds we aim to refine our therapeutic approach more conclusively to demonstrate the potential benefits in preclinical models as a step in the direction of human translation.
Favorite off-time activities:
Spending time with my family and friends. Recently - and unexpectedly - during COVID I have been exercising a lot, which I am enjoying quite a bit.
Best advice for new innovators & what I'm learning along the way:
In my lab, things begin with exploratory and curiosity-driven science, without a clear cut hypothesis. Our approach is to pay a lot of attention to technical innovations and develop novel methodologies . We especially like techniques and strategies that allow discoveries in the most unbiased way possible. Importantly, we do not like to be influenced much by dogmas and hot hypotheses. Instead, we pay attention deeply to the data. Any finding that is highly reproducible is likely to be important, no matter if it sounds boring.
Translational science, however, requires a significant change in mindset to a more focused and goal-oriented approach, which is sometimes difficult for labs like mine.
