Fox Chase Researcher Receives NIH Grant to Advance Treatment of Immune Diseases Using Genome Editing

A Fox Chase Cancer Center researcher has received a grant of approximately half a million dollars from the National Institutes of Health (NIH) to identify disease-causing T cell defects. The work will also involve developing genome editing as an improved and more personalized form of treatment of immune-related diseases.

Grant recipient David Wiest, PhD, Deputy Chief Scientific Officer at Fox Chase, will serve as the co-lead on the final phase of a three-part collaborative study subcontracted by the University of California, San Francisco.

The project will utilize the multidisciplinary expertise of Wiest and his lab to enhance understanding of how human T cells develop and to identify the defective gene that blocks development of the immune system in children with severe combined immunodeficiency (SCID) and related diseases. SCID is a life-threatening genetic disorder in which infants lack T and B lymphocytes.

"We hope that this approach paves the way for genome editing of the DNA of the child's hematopoietic stem cells as a therapy to correct the defective gene and restore the child's immune system," said Wiest.

They also hope the study will enable scientists to identify new genes that regulate immune cell development, which may be useful as therapeutic targets in immune-related diseases or even cancer.

Wiest's work will build on the findings from the second part of the study, in which the researchers will begin to identify what genes and mutations cause T cell insufficiency using CRISPR-based screening. CRISPR is an editing tool used to find a small number of genes inside many genetic sequences.

Wiest is responsible for overall administration and guidance of functional analysis of genes in zebrafish, a process which will validate the findings on which genes are essential to proper T cell development. He and his team will also utilize patient variants found through the CRISPR-based screening to determine if the variants prevented the genes from properly functioning.

Zebrafish are an increasingly popular organism used in research on human diseases. More than two-thirds of human genes can be found in the genetic makeup of zebrafish. The research will focus on re-expressing the human genes in the zebrafish to see if this can prevent developmental stunting when the essential genes in the zebrafish are lost.

The three-part project's use of a varied approaches, including screening of newborns, whole genome sequencing, and functional tests in zebrafish is to ensure the study is thorough. The ultimate goal, Wiest said, is improving how patients with these conditions receive treatment.

About Fox Chase Cancer Center

The Hospital of Fox Chase Cancer Center and its affiliates (collectively "Fox Chase Cancer Center"), a member of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation's first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center's nursing program has received the Magnet recognition for excellence five consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship and community outreach. It is the policy of Fox Chase Cancer Center, that no one shall be excluded from or denied the benefits of or participation in the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.