Written by: Beth Dougherty
Doctor-scientist Franziska Wachter, MD, got here to Dana-Farber 10 years in the past as a postdoctoral fellow with a imaginative and prescient. Within the clinic, she cares for youngsters with hard-to-treat circumstances of acute myeloid leukemia (AML). Within the laboratory, her eyes are on the molecular drivers of the illness.
“I attempt to join the 2 roles as a lot as I can,” explains Wachter. “I usually deal with sufferers with a excessive probability of relapse. My hope is to discover a option to forestall the leukemia from coming again.”
Wachter’s coaching, which has concerned scientific residency and stints in a number of Dana-Farber labs, blends stem cell transplant, biochemistry, and structural biology — a novel mixture that positions her to give attention to drug improvement. Nonetheless, such progressive work requires time and entry to classy know-how.
Wachter may have each as a result of, in recognition of her expertise, she was named to the 2024 Sidney Farber Students Program. This system goals to construct another pathway to school positions for tremendously gifted fellows and instructors who would thrive within the pursuit of impartial analysis in a supported, synergistic setting early on of their careers. The award can be supposed to encourage those that could take into account leaving tutorial analysis, particularly individuals who determine as feminine, to remain within the discipline. Wachter plans to pursue her personal initiatives within the laboratory of mentor and researcher Eric Fischer, PhD.
“The award provides me the time and scientific freedom to spend money on initiatives which are increased threat, however definitely promising,” says Wachter, who studied medication in Munich, Germany.
Zooming in on fusion
The pediatric leukemia circumstances Wachter treats usually start with what she calls a “catastrophic genomic occasion.” Two genes that aren’t often sure collectively fuse into one, kicking off a speedy course of that drives the event of most cancers.
The method, nonetheless, is just not simple. The management of typical cell biology entails the exact regulation of genes. Particular proteins work collectively, like an orchestral conductor, to cue the genome at vital moments and switch genes on and off. Fused genes can intervene with this course of, like a conductor with one hand tied behind their again.
Wachter’s work entails the microscopic inspection of those protein conductors to learn the way they perform. She has used X-ray crystallography to see proteins on the atomic stage and study their molecular construction. Now, she is utilizing cryo-electron microscopy to study extra about how giant protein complexes fuse collectively and drive AML. Cryo-electron microscopy entails freezing a number of copies of a protein pattern and bombarding them with an electron beam to create 3D fashions that may reveal each the protein’s construction and performance.
Oblique inhibitors
When a genetic course of goes awry and drives most cancers, there isn’t all the time a direct option to appropriate it with a drug. Lately, nonetheless, Scott Armstrong, MD, and others have found a option to inhibit a genetic course of that drives AML by blocking the exercise of a protein not directly concerned within the course of.
It took many years for the group of researchers behind this work to know the proteins and molecular processes concerned and to plot a option to block them. Wachter’s objective is to search out extra methods to cleverly intervene with the genetic drivers of pediatric blood cancers.
“There are numerous different laborious to deal with pediatric cancers which are additionally pushed by complicated genetic packages,” explains Wachter. “We now have to higher perceive the proteins and molecular processes concerned in these packages so we are able to develop molecules that block them.”
