At Vincere, I set strategy, recruit, and manage a team of world-class therapeutic discovery and development experts toward success in chemistry, in vivo pharmacology, disease efficacy studies, IND-enabling studies, clinical trial planning, and AI/ML projects that have delivered multiple small molecule programs targeting mechanisms that drive age-related decline with a lead program expected to enter the clinic within 18-24 months.

After almost a decade researching neurodegeneration, I came to a realization that if we are to defeat these complex diseases, we must develop and use the sharpest tools in the arsenal and this includes computational tools that are still not commonplace in drug discovery. I co-founded a computational drug discovery company, NI, alongside my husband who is a computer scientist. At NI we use several computational tools. Examples include: 1. physics-based simulation of neurons from patients and addition of potential therapeutics to assess their potential, 2. network analytics of the biochemical interactome and discovery of points of convergence in various forms of the disease, 3. AI/ML probing of multi-omics data to select patients who are most likely to respond to a particular therapeutic – this includes analysis of terabytes of proteomics, transcriptomics, genetic, methylomics, and other data that would not be possible without computational tools. This work includes multiple collaborative projects with University of Oxford, Mayo Clinic, Michigan State University, and Southern Research Institute. The company has raised private and grant funding.

My drug discovery experience deepened during my post-doctoral training at the Mayo Clinic with Dr. Farrer and an interdisciplinary team which included geneticists, animal modelers, and molecular biologists. Through a collaboration with H. Lundbeck Pharmaceuticals and Michael J. Fox Foundation, I worked with the team on characterization of LRRK2 inhibitors for the treatment of Parkinson’s disease. LRRK2 inhibitors now represent a promising therapeutic and are in Phase II clinical trial by Denali Pharmaceuticals. I also had a chance to learn alongside stellar geneticists and take part in discovery of multiple genetic contributors to Parkinson’s disease, including VPS35.

Not all dopamine neurons degenerate in Parkinson’s disease. What makes the degeneration-resistant cells such as A12 neurons special? and can this be leveraged to make the susceptible neurons resistant to further degeneration? This was the topic of my PhD dissertation in the lab of Dr. John Goudreau. I showed that the protected neurons required expression of proteins following neurotoxic insult (otherwise they degenerated). I used laser capture microdissection to collect susceptible (A9), partially protected (A10), and fully protected (A12 – TIDA) dopamine neurons and used microarray technology to determine which genes are upregulated only in the fully protected neurons. One of the upregulated genes was familiar: Parkin! Using stereotaxic lentiviral delivery, I was able to show that decreasing expression of parkin made the protected neurons susceptible to neurotoxicity. The work of other groups had also demonstrated that increasing parkin can protect the susceptible neurons. I received multiple awards for this work, including a coveted NIH National Research Service Award (NRSA), a research excellence award, and a dissertation completion fellowship. At the time, we had no idea how to increase parkin or its activity in people. But many years later I would co-found a drug discovery company, Vincere, to try to do exactly that. As a side project during my PhD, I also began my journey into drug development through a DoD funded collaboration with Pfizer for repurposing of existing medications such as Viagra for neurodegenerative diseases. It turns out Viagra was not neuroprotective in our Parkinson’s models – but it also didn’t cause any harm, suggesting Parkinson’s patients would likely be able to take Viagra without exacerbating the disease.