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Northwestern scientist wins Hartwell award to study pediatric leukemia

A Northwestern University Feinberg School of Medicine scientist, Panagiotis “Panos” Ntziachristos, an assistant professor of biochemistry and molecular genetics, is a winner of the 2017 Hartwell Individual Biomedical Research Awards.  

Ntziachristos won for his project “Splicing Errors and Drug Resistance in Acute Lymphoblastic Leukemia.”

The award, one of 12 awarded by The Hartwell Foundation, provides research support for three years at $100,000 direct cost per year. 

In addition, by winning the Individual Award, Northwestern has qualified to receive a Hartwell Fellowship that provides postdoctoral support for two years at $50,000 direct cost per year to a candidate who holds a Ph.D. and/or equivalent doctorate and will pursue further specialized training in biomedical research.

Each year, more than 3,000 children in the U.S. are diagnosed with acute lymphoblastic leukemia (ALL). As the most prevalent malignancy among children younger than 15, ALL is a cancer that starts with an increase in the proliferation of immature white blood cells (lymphocytes) from the bone marrow, where new blood cells are made. The abnormal cells are unable to function properly and crowd out healthy cells, causing anemia, bruising and bleeding, fever and an inability to fight infection.

Current research on the development of ALL focuses mainly on mutated genes and the first step in their level of expression (transcription), where a strand of DNA nucleic acids is copied into a new molecule of messenger RNA (mRNA). Each mRNA transcript specifies the amino acid sequence of a protein product and serves as a template for protein production (translation).

For approximately 95 percent of transcripts, portions of intervening DNA (introns) must be removed after transcription, with the final remaining mRNA consisting of spliced sequences of DNA (exons) connected to one another. This process is similar to combinations of notes and syllables that create "words" and "phrases." Longer combinations of those "words" can create "sentences" and combinations of those create a "verse." Splicing of pre-mRNA is catalyzed by complexes assembled from five small RNA molecules and numerous protein factors. 

Ntziachristos has discovered that the amount of protein splicing factors increases in aggressive disease compared to the time of diagnosis, leading to splicing errors, similar to errors in combinations of words leading to wrong sentences. This aberrant process might be responsible for drug resistance. Such errors may not only contribute to cancer initiation and progression but also have the potential to affect tumor suppressor genes and enzymes that can make disease refractory to chemotherapy.

In his project, Ntziachristos will characterize the mechanisms of this process and determine the effect of small molecule inhibitors on protein levels of the splicing machinery in leukemia, and whether therapy can be improved using the inhibitors in combination with chemotherapy.

“If I am successful in developing a new targeted therapy for children diagnosed with ALL, it will improve clinical outcomes by reducing relapse, while extending the quality of their lives,” Ntziachristos said. "I am very grateful for the support of The Hartwell Foundation.”

“The Hartwell Foundation seeks to inspire innovation and achievement by offering individual researchers an opportunity to realize their professional goals,” said Fred Dombrose, President of The Hartwell Foundation.

In selecting awardees, the foundation considers the compelling and transformative nature of the proposed innovation, the extent to which a strategic or translational approach might accelerate the clinical application of research results to benefit children of the U.S., the extent of collaboration in the proposed research, the institutional commitment to provide encouragement and technical support to the investigator and the extent to which funding the investigator will make a difference.

The award funding counts toward We Will. The Campaign for Northwestern, Northwestern’s university-wide fundraising initiative. The funds raised through the “We Will” Campaign are helping realize the transformational vision set forth in Northwestern’s strategic plan and solidify the University’s position among the world’s leading research universities. 

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