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Jill Zitzewitz is unraveling protein misfolding to understand disease

Funded by ice bucket challenge, ALS researcher working to development therapies

By Megan Bard

UMass Medical School Communications

January 30, 2017

The Women in Science video series on UMassMedNow highlights the many areas of research conducted by women at UMass Medical School.

Jill A. Zitzewitz, PhD, associate professor of biochemistry & molecular pharmacology, is working to decipher the molecular basis of protein misfolding diseases, such as amyotrophic lateral sclerosis (ALS) and Alzheimer’s.

Determining why some proteins misfold and how this leads to disease will help scientists develop therapeutic small molecules and antibodies to treat disease.

Dr. Zitzewitz’s research efforts use biophysical methods to probe the folding, misfolding and aberrant aggregation processes in ALS variants with particular emphasis on TDP-43, a protein associated with many nonfamilial or sporadic cases of ALS.

“We are trying to understand the conformations and shapes of proteins and what they’re normally supposed to be doing,” said Zitzewitz, who opened her lab at UMMS in 2001. “Are there any partially-folded or misfolded forms that have an important function for some reason or are there some situations that might make a protein vulnerable to misfolding and disease processes?”

With funding from the ALS Association that was primarily raised through the Ice Bucket Challenge, Zitzewitz is trying to develop a small molecule screen that could target the TDP-43 protein.

She said she is especially motivated in her studies by patients and their families.

“The work has really moved more into taking the fundamental biophysics that we understand well as far as how proteins fold and behave to try to really track when things go wrong,” she said.

As a mentor, Zitzewitz said some of the research accomplished in her lab can be credited to “one graduate student at a time.” Zitzewitz, who serves as a co-chair of the university’s Women’s Faculty Committee and teaches molecular biophysics, has mentored more than a dozen undergraduate and high school students in the lab and said one of her goals is to work on the pipeline of women in science.

“I want to provide greater opportunity for people to be in the lab, to experience the STEM fields,” she said, adding that she takes pride in helping students find their passion.

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