2020 HDSA Berman-Topper Fellow
University of Massachusetts Medical School
Mentors: Neil Aronin, MD, and Michael Brodsky, Ph.D.
What initially inspired you to enter into HD Research, and, since entering the field, what experiences have brought you to your current point in your career?
After getting my bachelor’s degree in Chemistry from Shiraz University in Iran, I joined the University of Massachusetts Amherst as a Ph.D. student in Biological Chemistry. During the Ph.D., my main area of research was on understanding the mechanistic enzymology of T7 RNA polymerase and developing tools to improve in vitro RNA synthesis for therapeutic applications. Being actively involved in the field of RNA therapeutics and learning about recent revolution in RNA-based therapeutics made me very excited about the applications of RNA in biomedical research. I am also interested in understanding the underlying mechanisms of neurodegenerative diseases and developing therapeutic tools to target such diseases. After receiving my Ph.D., I started my postdoctoral training with Dr. Neil Aronin and Dr. Michael Brodsky at the University of Massachusetts Medical school, where I have been able to both apply and expand my skills to develop new CRIRSPR-Cas9 genome editing tools to correct the mutant Huntingtin gene back to the wild type gene. I am grateful for having the opportunity to work with my mentors where I can gain knowledge in both the molecular aspects of gene editing and the pathophysiology and clinical manifestations of Huntington’s disease.
In layman’s terms, please tell us some highlights about your HDSA-funded project. What is the potential impact of your project on the field of HD research and/or clinical outcomes for persons with HD?
CRISPR-Cas9 genome editing is a promising technology with the potential to treat genetic diseases by changing the DNA mutation that is the underlying cause of the disease. HD is caused by a CAG repeat expansion in Exon 1 of the Huntingtin gene. Our goal is to apply CRIRSPR-Cas9 genome editing tools to correct the mutant Huntingtin gene back to the wild type gene by reducing the number of CAG repeats to below the pathogenic threshold. We have very promising results in HD patient cells, and we are currently working on making the method work more efficiently in animal models. In one line of experiments, we are working on modulating cellular DNA repair pathways to probe the mechanism of induced repeat length contractions and identify reagents to improve this activity in the brain. Additionally, current approaches for delivery of these gene editing tools to the brain have challenges such as safety concerns due to continuous expression of these gene editing complexes. Therefore, we are concurrently, developing a new technique to deliver CRISPR-Cas9 gene editing tools to the brain in the form of ribonucleoprotein (RNP) complexes. This method will potentially reduce safety concerns due to short half-life of RNPs and promote uptake and distribution of editing throughout brain. If successful, a single treatment could revert the CAG repeat in mutant Huntingtin gene to the normal range. This approach will have therapeutic uses for HD and other neuropathological disorders associated with trinucleotide repeat expansions.
What do you like most about your work or the HD research field, and what is your biggest challenge?
I am hopeful that my research will lead to the development of therapeutic tools for HD patients to improve the quality of their life. This is highly rewarding and motivating for me. Of course, in research, we don’t always get the results we expect, which can be challenging sometimes. I try to overcome this challenge by reminding myself of the ultimate goal and the impact my work can potentially have.
What are your biggest goals as you move forward in your career, or major areas of interest for future research?
I’m very passionate about developing new drugs for diseases with no cures yet. I hope to continue a research career leading to development of new therapeutics to improve the lives of individuals with HD and other similar diseases.
When you’re not working on HD research, what do you do for fun?
I really enjoy outdoor activities such as hiking. I also recently got married and my husband and I really enjoy cooking together.
What has the grant support from HDSA meant to you?
I am very grateful and honored for receiving this grant from HDSA. The generous support from Berman-Topper HD Career Development Fellowship has allowed me to pursue my research goals while, at the same time, preparing me for my future career. The fellowship has also provided me an opportunity to interact with other Berman Topper fellows. Getting to know these wonderful researchers, discussing our research progress, and sharing ideas with each other, have been both very helpful and very inspiring for me.