Printed: June 26, 2024
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 kids with hard-to-treat instances 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 typically deal with sufferers with a excessive probability of relapse. My hope is to discover a method to stop the leukemia from coming again.”
Wachter’s coaching, which has concerned medical 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 concentrate on drug improvement. Nonetheless, such modern work requires time and entry to stylish 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 college positions for tremendously proficient fellows and instructors who would thrive within the pursuit of impartial analysis in a supported, synergistic atmosphere early on of their careers. The award can be supposed to encourage those that could think about 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 offers me the time and scientific freedom to spend money on initiatives which can be greater threat, however actually promising,” says Wachter, who studied drugs in Munich, Germany.
Zooming in on fusion
The pediatric leukemia instances Wachter treats typically start with what she calls a “catastrophic genomic occasion.” Two genes that aren’t normally certain collectively fuse into one, kicking off a speedy course of that drives the event of most cancers.
The method, nevertheless, will not be easy. 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 intrude 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 find out how they operate. She has used X-ray crystallography to see proteins on the atomic degree and be taught their molecular construction. Now, she is utilizing cryo-electron microscopy to be taught extra about how massive 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 method to right it with a drug. Just lately, nevertheless, Scott Armstrong, MD, and others have found a method 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 grasp the proteins and molecular processes concerned and to plan a method to block them. Wachter’s purpose is to search out extra methods to cleverly intrude with the genetic drivers of pediatric blood cancers.
“There are lots of different exhausting to deal with pediatric cancers which can be additionally pushed by complicated genetic applications,” explains Wachter. “We have now to higher perceive the proteins and molecular processes concerned in these applications so we will develop molecules that block them.”