Aaron Hobbs, Ph.D.

Assistant Professor
Department: Cell & Molecular Pharmacology
Programs: Cellular Injury, End Organ Disease

 

 

Research Interests:

The primary focus of the Hobbs lab is on KRAS mutant-specific signaling in pancreatic cancer. His work demonstrating that KRAS G12R (KRASG12R) efficiently promotes PDAC but not other cancers is paradigm-shifting for the RAS field. He plans to utilize common and rare KRAS mutations to study pancreatic cancer tumorigenesis and better understand how to stop the proliferation of PDAC. Pancreatic cancer has a five-year overall survival rate of 12%, highlighting the need for effective therapeutic strategies. Mutational activation of the KRAS proto-oncogene is the initiating event in PDAC, and ~95% of patients harbor KRAS mutations. KRASG12R is the third most common KRAS mutation in PDAC, representing 20% of cases, yet is rare in KRAS-mutant lung and colorectal cancers (<1%). Dr. Hobbs’ published data support KRASG12R as a potent PDAC driver. However, all KRAS mutations are not created equal. He has shown that KRASG12R cannot interact with the lipid kinase PI3Ka, a well-characterized RAS effector thought to be necessary for KRAS-driven PDAC tumorigenesis. Thus, he has hypothesized that additional pancreas cell-specific mechanisms promote constitutive PI3K activity, allowing KRASG12R to promote PDAC development despite not activating PI3K directly. He has recently found that all four class I PI3K isoforms are expressed in PDAC and appear to function redundantly to promote proliferation.

Dr. Hobbs’ lab has additionally focused on micropinocytosis, a process tightly linked to KRAS. In this work, it appears that 2 different micropinocytosis pathways are active in PDAC – and both are targets of potential therapeutic intervention.

The specificity of the KRAS G12R mutation to pancreas cancer highlights Dr. Hobbs’ overall research objective, the development of mutation-specific therapies. His research efforts will provide new biologically meaningful targets for the development of therapies targeting individual KRAS mutations and his laboratory seeks to answer these questions using a unique array of multi-disciplinary approaches, including protein biochemistry, structure biology, cell signaling, organoids and mouse models.

Publications:

PubMed Collection