2020 Grantee: Alexander Muir, PhD
University of Chicago
Research Project: Microenvironment Induced Metabolic Requirements of Pancreatic Cancers
Award: 2020 Pancreatic Cancer Action Network Career Development Award
Award Period: July 1, 2020 – June 30, 2022
Dr. Alex Muir is an assistant professor in the Ben May Department for Cancer Research at the University of Chicago. He earned his PhD in biochemistry, biophysics and structural biology from the University of California, Berkeley. There, he trained with Dr. Jeremy Thorner, studying the metabolism (what nutrients are taken up by cells and how they are digested by the cell) of fungi as they adapt and cope with stressful changes in their environment. He then trained as a postdoctoral fellow under Dr. Matthew Vander Heiden at MIT, where he developed expertise in studying the metabolic adaptations that cancer cells use to survive in the harsh environment of tumors.
The Muir lab now works to comprehensively identify the critical nutrients and metabolic pathways that pancreatic cancers require to survive the tumor environment, towards the goal of finding metabolic drugs and tailored diets to treat pancreatic cancer patients.
Compared to healthy organs, pancreatic cancers have a unique local microenvironment that is characterized by substantial fibrosis (structural tissues) and abnormal vasculature (blood vessels). Thus, not only are the pancreatic cancer cells themselves mutated, but the environment they occupy is abnormal as well.
This suggests researchers could therapeutically target pancreatic tumors on the basis of their microenvironment while sparing normal organs lacking such abnormalities. Unfortunately, scientists have not known enough about the microenvironment of pancreatic tumors to realize the goal of exploiting microenvironmental differences for therapeutic gain.
To better understand the microenvironment of pancreatic tumors, Dr. Muir and his team recently developed techniques to measure nutrient levels in the microenvironment of tumors and healthy tissues. They found that pancreatic tumors indeed have a unique nutrient microenvironment compared to the rest of the body. Now, they seek to identify the cellular processes that pancreatic tumors specifically require for growth and survival in their unique nutrient environment.
Dr. Muir and colleagues will use metabolic studies (looking at ways pancreatic cancer cells and their microenvironment break down and utilize nutrients differently from healthy cells) and advanced CRISPR-based genetic screening approaches (a way to locate and disrupt specific sequences of DNA) to leverage this new microenvironmental information.
Collectively, these experiments will provide new insight into the metabolism underpinning pancreatic cancer and identify a new class of therapeutic targets exploiting the unique microenvironment of pancreatic tumors.