By Leo Barolo
Among the bright spots of the last year is the arrival of two new faculty working at the cutting edge of genomic technology and its application.
Dr. Gaelen Hess, Assistant Professor in the Department of Biomolecular Chemistry, and Dr. Muhammed Murtaza, Associate Professor in the Division of Surgical Oncology, are the first faculty hired into the Center for Human Genomics and Precision Medicine. Both faculty bring unique perspectives to the mission of the Center, which is to deliver precision medicine that leverages a person’s genome sequence to patients in Wisconsin.
Hess’s research investigates linkages between genotype and phenotype to uncover fundamental biology and improve human health. Motivated during his Ph.D. at Harvard in Angela Belcher’s lab and postdoctoral work in Michael Bassik’s lab at Stanford, Hess is developing and applying novel tools in CRISPR-directed deep mutagenesis and high-throughput screening in mammalian cells. He and colleagues invented CRISPR-X, an approach that uses catalytically inactive Cas9 (dCas9) to direct a cytidine deaminase (AID) to specific sites in the genome. The system can generate libraries of local point mutations within cells. Coupled with high-throughput phenotyping and sequencing, CRISPR-X can rapidly distinguish functional DNA variants from inactivated mutants. Hess and colleagues have applied these and other genome engineering strategies to a range of biological problems, from understanding how mutant cells become resistant to chemotherapies to how human transcription factors regulate gene expression.
Hess is excited to launch his research program at UW-Madison to apply these tools to understand functional constraints of DNA repair pathways, pathogenic microbial effectors that alter host cell functions, and therapeutic responses to drugs and treatments.
This knowledge will advance our understanding of the effects of mutations in human patients, helping to accelerate diagnostics and treatment strategies.
“I have always been fascinated by the diversity in nature … [and the] numerous elegant solutions to so many biological problems.” – Dr. Hess
Murtaza’s research and approach to precision medicine comes from a different angle: developing new methods for cancer detection in patients in Wisconsin and beyond. Patients with cancer benefit from early detection so that treatment can mitigate disease spread. But for many cancers, early detection is a problem – simply stated, there aren’t good methods to catch the disease before it advances.
Before coming to UW-Madison, Murtaza developed a strong research program as a faculty member at the Translational Genomics Research Institute (TGen) in Phoenix, Arizona. His expertise is developing cutting-edge genomic and computational methods for detecting tumor DNA that is shed into blood, urine and other body fluids in patients with cancer. The circulating tumor DNA can be used as a marker to indicate cancer type and also tumor load. Early applications can both diagnose cancer in the early stages and also track tumor burden as patients undergo treatment, providing an early indication if treatment methods are working.
Despite the promise of tracking circulating tumor DNA, there are significant challenges in detecting small amounts of material and identifying the cancer type based on DNA sequence. Murtaza’s research has developed new sequencing-based methods as well as computational innovations in analyzing the data. Murtaza’s research will continue to push the boundaries of using circulating tumor DNA to influence patient care. Toward this aim, he is also the Co-Director of the Center’s Novel Diagnostics Program.
“What attracted me towards cancer biomarker development was realizing how the field was so ripe for innovation and rapid translational advances into clinical practice.” – Dr. Murtaza
The Hess and Murtaza Labs are housed in the WIMR West Wedge building within the Center for Human Genomics and Precision Medicine.