Sidney Farber Scholar Pursues Innovative Treatments for Leukemia 

Physician-scientist Franziska Wachter, MD, came to Dana-Farber 10 years ago as a postdoctoral fellow with a vision. In the clinic, she cares for children with hard-to-treat cases of acute myeloid leukemia (AML). In the laboratory, her eyes are on the molecular drivers of the disease.  

“I try to connect the two roles as much as I can,” explains Wachter. “I often treat patients with a high chance of relapse. My hope is to find a way to prevent the leukemia from coming back.” 

Wachter’s training, which has involved clinical residency and stints in multiple Dana-Farber labs, blends stem cell transplant, biochemistry, and structural biology — a unique combination that positions her to focus on drug development. However, such innovative work requires time and access to sophisticated technology.  

Wachter will have both because, in recognition of her talent, she was named to the 2024 Sidney Farber Scholars Program. The program aims to build an alternative pathway to faculty positions for tremendously talented fellows and instructors who would thrive in the pursuit of independent research in a supported, synergistic environment early on in their careers. The award is also intended to encourage those who may consider leaving academic research, especially people who identify as female, to stay in the field. Wachter plans to pursue her own projects in the laboratory of mentor and researcher Eric Fischer, PhD. 

“The award gives me the time and scientific freedom to invest in projects that are higher risk, but certainly promising,” says Wachter, who studied medicine in Munich, Germany.  

Zooming in on fusion 

The pediatric leukemia cases Wachter treats often begin with what she calls a “catastrophic genomic event.” Two genes that are not usually bound together fuse into one, kicking off a rapid process that drives the development of cancer.  

The process, however, is not straightforward. The control of typical cell biology involves the precise regulation of genes. Specific proteins work together, like an orchestral conductor, to cue the genome at critical moments and turn genes on and off. Fused genes can interfere with this process, like a conductor with one hand tied behind their back.  

Wachter’s work involves the microscopic inspection of these protein conductors to learn how they function. She has used X-ray crystallography to see proteins at the atomic level and learn their molecular structure. Now, she is using cryo-electron microscopy to learn more about how large protein complexes fuse together and drive AML. Cryo-electron microscopy involves freezing multiple copies of a protein sample and bombarding them with an electron beam to create 3D models that can reveal both the protein’s structure and function. 

Indirect inhibitors 

When a genetic process goes awry and drives cancer, there isn’t always a direct way to correct it with a drug. Recently, however, Scott Armstrong, MD, and others have discovered a way to inhibit a genetic process that drives AML by blocking the activity of a protein indirectly involved in the process.  

It took decades for the team of researchers behind this work to understand the proteins and molecular processes involved and to devise a way to block them. Wachter’s goal is to find more ways to cleverly interfere with the genetic drivers of pediatric blood cancers.  

“There are many other hard to treat pediatric cancers that are also driven by complex genetic programs,” explains Wachter. “We have to better understand the proteins and molecular processes involved in these programs so we can develop molecules that block them.”