Mario Shields
Stony Brook University, NY·Medicine & Clinical Research
Pancreatic cancer is aggressive, and patients have few treatment options. One overlooked player is Gα13, a G protein that relays signals from G protein-coupled receptors (GPCRs).
- Fields
Medicine & Clinical Research
Pharmacology
Biochemistry
- Topics
pancreatic cancer
pancreatic ductal adenocarcinoma
Gα13
- Grants
- 1 known grant, through Jul 2028
What they work on
- Test whether blocking mTORC1 signaling delays tumor development and causes cell death in early and advanced pancreatic tumors lacking the G protein Gα13, using a genetic mouse model of pancreatic cancer.
- Determine how Gα13 loss changes tumor metabolism and whether Gα13-deficient pancreatic tumors are especially vulnerable to drugs that disrupt mitochondrial function.
- Measure whether Gα13 loss raises inflammatory cytokines and tumor-promoting immune cells, and whether mTORC1 inhibition limits these to suppress tumor growth.
- Test whether combining anti-inflammatory agents with mitochondrial inhibitors enhances anti-tumor effects, and use human tumor slice cultures to see if Gα13 status predicts response to mTORC1 inhibition.
More about the research
GPCRs are the largest class of cell-surface receptors and a major target of approved drugs. In some cancers Gα13 promotes tumors; in others it suppresses them. The lab previously reported that removing Gα13 in a genetic mouse model of pancreatic cancer sped up tumor growth and shortened survival. These tumors showed high mTOR signaling, a growth-control pathway that is also elevated in human pancreatic cancer, and they responded to the mTOR inhibitor rapamycin. The team also found that losing Gα13 increased mitochondrial metabolism and production of inflammatory cytokines, signaling molecules that drive inflammation.
Why it matters
Patients with pancreatic cancer have few effective treatments. Learning how Gα13 loss drives tumor growth through mTORC1, metabolism and inflammation could reveal which patients' tumors are vulnerable to mTORC1 inhibitors, mitochondrial inhibitors or anti-inflammatory drugs. It could also point to combination therapies for patients whose tumors lack Gα13.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Wantong Yao
University of Texas MD Anderson Cancer Center, TX·Medicine & Clinical Research
Define the molecular pathways through which a newly identified stress-response regulator helps pancreatic ductal adenocarcinoma (PDAC) cells survive nutrient shortage, low oxygen and oxidative stress, and evade the immune system.
Andrew Lowy
University of California-San Diego, CA·Medicine & Clinical Research
Test whether deleting MICAL2, an actin-dismantling enzyme, blocks or delays KRAS-driven pancreatic tumor formation and progression, using whole-body and conditional deletion in genetically engineered mice.
Brittany Allen-Petersen
Purdue University, IN·Biochemistry
Identify how PP2A-B56α, a subunit of a phosphate-removing enzyme, controls the fusion of macropinosomes with lysosomes, focusing on chemical changes made to proteins after they are built.
The school
Stony Brook University: 32 labs on PI Pages, $319M a year on research, 289 research doctorates a year.
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