Jay Mahat, PhD: Adopting a ‘Mountaineer’s Code’ to Reach New Heights in Gene Regulation Research

Digbijay (Jay) Mahat, PhD, recently joined Columbia University as an assistant professor in the Department of Systems Biology. As a new member of the Herbert Irving Comprehensive Cancer Center (HICCC) Cancer Genomics and Epigenomics (CGE) program, Mahat’s research explores how changes in gene activity contribute to immune system diseases. He holds a joint appointment at Biohub, New York, researching non-coding regions of the genome in regulating gene expression in cancer and autoimmune diseases. 

Shifting Focus to Genomics 

Before coming to Columbia, Mahat earned his PhD at Cornell University. He completed his postdoctoral work primarily at the Koch Institute for Integrative Cancer Research of MIT and jointly with the Broad Institute of MIT and Harvard towards the end of his training, initially developing a single cell method of nascent RNA sequencing. While working on this pursuit, Mahat decided that he needed a backup plan. Inspired by the research of Dr. Tyler Jacks’ lab, Mahat started to think about cancer initiation and progression from the perspective of gene regulation.  

“My training has always been on gene regulation, how various parts of the genome, like coding genome, non-coding genome come together to orchestrate a gene program that cancer seems to hijack almost all the time,” said Mahat.  

The subsequent project, to study the mutant P53 protein that helps cancer cells survive, came out last year in the journal Immunity. With it, a new understanding of looking at cancer from the angle of coding and gene regulation came into view for Mahat – and has since become the focus of his work at Columbia and at Biohub. 

By researching the coding elements that infiltrate tumors, identifying cancer protein “flags,” and drug development, Mahat and his colleagues are making strides towards better treatment through cancer genomics.  

“We have various angles of this work that all converge in the domain of cancer biology, understanding it and reprogramming,” said Mahat.  

Coming to Columbia 

The ability to conduct his research at both Columbia and Biohub was key for Mahat when choosing where to set up his lab. He was particularly drawn to Columbia for the immense resources available to researchers and the rich educational environment of a medical school.  

“Two particular reasons that Columbia stood out was one, the larger ecosystem of medical scientists and physicians working together with access to the patient samples,” said Mahat. “And number two, being able to do this work simultaneously at both Columbia and Biohub. 

Within the HICCC, researchers have access to patient-derived samples through the university’s biobanks, enabling them to use real biological data from human beings in trials and translational research.  

The Mahat Lab 

In the untrodden world of research, the Mahat Lab enlists a shared identity based around the pillars of curiosity, collaboration, and mentorship.  

These key characteristics guide their research goals which investigate the dysregulation of gene programs and novel therapies in the context of pancreatic cancer, colon cancer, and other cancers of the gastrointestinal tract. 

Currently, Mahat is leading the way on several projects. One such project seeks to identify and disarm enhancers that suppress the immune system in pancreatic ductal adenocarcinoma, a common and aggressive form of pancreatic cancer.  

The lab also highlights their efforts to develop new cancer mapping technologies, making use of artificial intelligence and machine learning to build virtual cell models and multimodal single-cell genomic assays. 

While maintaining a robust research profile, Mahat also emphasizes the importance of mentorship and storytelling in science. 

Mahat asks his students what story they want to tell and who they’re telling it to. He urges them to question what the data represents beyond the numbers.  

“We have to be able to communicate science effectively, so I try to instill in my research fellows the importance of telling the story in a way that resonates with the kind of audience you have [when sharing research],” said Mahat. 

The Mountaineers’ Philosophy 

Hailing from a village in Nepal, Mahat grew up with views of Fishtail Mountain from his window and a deep connection to mountaineering culture. He sees many parallels between climbing and scientific discovery.  

"These terrains are uncharted. It's difficult, it's hard, but the joy of being there and being able to succeed is exhilarating,” said Mahat. "It’s something that I want to replicate and follow when we are pursuing difficult scientific questions in a lab.”  

His lab philosophy adopted from the “Mountaineer's Code” follows that of a climber, dependent on teamwork and perseverance to achieve its mission. 

“It's an ode to, and reflection of, where I come from. Every expedition relies on resilience, trust, and patience to endure storms both unexpected and unforeseen," said Mahat. 

When approaching an unexplored question in research, the Mahat Lab keeps their explorative spirit alive. Lifting themselves – and their research – to new heights.