Prof. Sachs secures more than $6 million to advance molecular therapeutics

An infusion of new funds for BME Professor Jonathan Sachs aims to advance scientists’ understanding of molecular dynamics and develop new drugs for treating neurodegenerative diseases, including Alzheimer’s and Parkinson’s, and inflammatory conditions such as rheumatoid arthritis. 

In less than two years, Prof. Sachs secured more than $6 million—a figure that includes child projects, subawards, and supplements—through a variety of funding mechanisms, including an NIH Maximizing Investigators' Research Award (MIRA) R35, two NIH R01s, and the Small Business Innovation Research (SBIR) program. 

Projects—and Prof. Sachs’ research efforts more broadly—aim to turn fundamental physics into cures for human disease by combining experimental biophysics, cell biology, and computational modeling using some of the world’s fastest supercomputers.

Advancing knowledge of protein dynamics

A recent NIH Maximizing Investigators' Research Award (MIRA) R35 award for more than $1.8 million is enabling Prof. Sachs and his lab to better understand the structural dynamics of Tumor Necrosis Factor (TNF) receptors. This family of proteins is an essential regulator of inflammation that can lead to diseases such as rheumatoid arthritis and cancer if they malfunction.

The project builds on Prof. Sachs’ previous work, which has fundamentally altered the view of how TNF receptors function. Further advancing this knowledge could one day help engineer novel drugs that target specific molecular motions and avoid activating unwanted and unrelated molecular processes. This has the potential to eliminate some dangerous side effects of current therapeutics, a finding published in Science Signaling.

In addition to the R35, Prof. Sachs recently received an R01 from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) for more than $2.7 million to advance his research on TNF receptors in collaboration with UMN’s Ben Hackel. He’ll also be collaborating with Bryce Binstadt, UMN Medical School, and David Ferguson, UMN Pharmacy, to engineer a drug that builds off his team’s findings, thanks to support from an internal grant from the UMN Office of Academic Clinical Affairs.

Understanding the molecular dynamics of neurodegenerative diseases

Prof. Sachs is using the same technological tools his team developed to study the dynamics of TNF receptors to monitor the molecular dynamics of toxic protein aggregates, such as those that cause neurodegenerative diseases like Alzheimer’s and Parkinson’s.

His lab was one of the first to demonstrate that small molecules can target tau aggregates and protect human neuronal cells from the toxic effects of aggregation through research published by Alzheimer’s & Dementia. Now, Prof. Sachs is building on this technology with an R01 from the National Institute of Neurological Disorders and Stroke (NINDS) called"Exploiting new fibril structures to understand the biophysical basis for oligomerization and toxicity of alpha-Synuclein."  Recent work on small molecules targeting Synuclein aggregates will be published soon in npj Parkinson’s Disease (part of Nature Partner Journals).

In addition, a project with Photonic Pharma has been awarded an extension of their SBIR Phase I grant from the National Institute of Aging. Prof. Sachs is partnering with the Minneapolis-based drug development company to help discover new therapeutic avenues for treating Alzheimer's and Parkinson’s. 

Finally, he’s received a child award through a National Heart, Lung, and Blood Institute R21 to BME Prof. Dave Wood. Together, they’ll be studying HbS oligomers as a therapeutic target for the treatment of sickle cell anemia.

More about Prof. Sachs’ research

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