2022 Milton Safenowitz Postdoctoral Fellowship Program for ALS Research Recipients
The ALS Association is proud to support the development of bright, early career scientists through the Milton Safenowitz Postdoctoral Fellowship. This award provides a maximum of $150,000 over two years to postdoctoral fellows in the ALS field.
The Safenowitz family established the award in memory of Milton Safenowitz, who died of ALS in 1998. These fellowships encourage and pave the way for promising scientists to enter the ALS field. Fellows work with a senior mentor and build connections within the ALS research community through meetings and presentations.
After completing this fellowship, more than 75% of awardees stay in ALS research. Many have gone on to establish their own laboratories and mentor more ALS researchers along the way, while others have gone on to careers in industry, nonprofits or medical writing.
Caiwei Guo, Ph.D.
Stanford University
Stanford, CA
Caiwei earned her Ph.D. in neuroscience from Baylor College of Medicine in 2020. Now under the mentorship of Dr. Aaron D. Gitler at Stanford, Caiwei is focused on better understanding how TDP-43 is involved in neurodegeneration.
TDP-43 is a protein normally found in the nucleus of nerve cells. It plays an important role in the processes neurons use to turn the “blueprints” found in DNA into shorter RNA templates that direct protein production. In people with ALS, TDP-43 exits the nucleus, becomes misshapen and clumps together with other proteins to create aggregates, a pathological feature found in 97% of people with ALS. Recent studies have shown that these aggregates disrupt the normal role TDP-43 plays in RNA splicing, a process that cuts out any genetic code that isn’t needed to produce a protein. This often leads to the inclusion of extra snippets of inappropriate sequences that are normally removed from RNA, called cryptic exons, which can cause neuronal dysfunction and loss.
The Gitler lab recently identified a set of 65 genes that are affected by cryptic RNA splicing in people with ALS and frontotemporal dementia. Using this gene set, Caiwei will investigate how cryptic splicing contributes to neuronal dysfunction and neuronal death in these diseases. She also will look for other proteins that suppress or enhance cryptic splicing. This knowledge could be used to generate novel therapeutic strategies.
Miriam Linsenmeier, Ph.D.
University of Pennsylvania
Philadelphia, PA
Miriam earned her Ph.D. in biochemical engineering from ETH Zurich in 2022. Now a postdoctoral fellow in the lab of mentor Dr. James Shorter, she is interested in determining if the misfolded TDP-43 proteins found in neuronal aggregates could be an effective therapeutic target. Her project will focus on utilizing a class of molecules called nuclear import receptors to restore TDP-43's natural shape and return it to its usual location and function. Miriam intends to identify nuclear import receptors that naturally target TDP-43 and understand how they work at a molecular level. She then will modify the top candidate to create an optimized variant that is highly efficient and specific. These results could pave the way toward new drug candidates for ALS.
Anuradhika Puri, Ph.D.
Washington University in St. Louis
St. Louis, MO
Anuradhika earned her Ph.D. in molecular genetics and biochemistry from the Institute of Microbial Technology in Chandigarh, India in 2021. Under the mentorship of Dr. Meredith Jackrel, she now is studying a way to reverse the clumping of misshapen TDP-43 and FUS proteins in motor neurons and prevent the cellular toxicity of these clumps, also known as aggregates. Anuradhika’s research focuses on HtrA1, a type of enzyme known as a disaggregase, which helps restore cellular proteins to their proper shapes. Recently, it was shown that HtrA1 can dissolve the toxic clumps of tau protein associated with Alzheimer’s disease. Initial data from the Jackrel lab has shown that HtrA1 also may be able to clear clumps of ALS-associated proteins like TDP-43 and FUS. For her project, Anuradhika is investigating how HtrA1 detoxifies TDP-43 and FUS. She also plans to engineer several variations of HtrA1 to better unravel TDP-43 and FUS aggregates, which could contribute to the development of new ALS therapies.
Kevin Rhine, Ph.D.
University of California San Diego
La Jolla, CA
Kevin earned his Ph.D. in biology from Johns Hopkins University in 2022. Now a postdoctoral researcher in Dr. Gene Yeo’s lab, Kevin is focused on gaining a clearer understanding of why aging is a major risk factor for ALS. To do this, he plans to turn skin cells from people with ALS into “aged” neurons so he can investigate the types of RNAs and proteins responsible for neuronal aging and how they interact with the RNAs and proteins that underlie the development of ALS. This aged neuron model also could be used to screen potential ALS treatments much more quickly than using mouse models.
Jayakrishna Shenoy, Ph.D.
Brown University
Providence, RI
Jayakrishna earned his Ph.D. from the University of Bordeaux in structural biology/solid-state NMR spectroscopy in 2020. Now under the mentorship of Dr. Nicolas Lux Fawzi at Brown University, Jayakrishna is interested in better understanding the structure of TDP-43. Currently, there are no high-resolution structural data showing how TDP-43 assembles to perform its healthy functions in neurons or how this process transitions into aggregation in people with ALS. Jayakrishna is aiming to change that using integrated experimental and computational structural biology techniques combined with molecular and cell biology approaches. The results of this project can then be applied to help guide the development of new strategies to treat and prevent TDP-43 aggregation.
