Andrew Lowy
University of California-San Diego, CA·Medicine & Clinical Research
Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is the deadliest common cancer. Fewer than one in ten patients survive five years.
- Fields
Medicine & Clinical Research
Biochemistry
Biophysics
- Topics
pancreatic cancer
pancreatic ductal adenocarcinoma
acinar-to-ductal metaplasia
- Grants
- 2 known grants, through Jul 2031
What they work on
- 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.
- Identify which functional domains of MICAL2 are needed to promote pancreatic cancer, using new cell lines that carry mutant MICAL2 constructs.
- Determine how MICAL2 drives acinar-to-ductal metaplasia, an early precancerous cell change, through actin remodeling by RAC1 and ARP proteins, EGFR and PI3K/AKT signaling, and mapping of MICAL2-dependent kinase circuits.
- Predict, using multiscale computational models, how MICAL2 changes cytoskeleton organization and cell mechanics during early pancreatic cancer, and test those predictions experimentally.
- Determine how MICAL2 changes the stickiness of pancreatic cancer cells and their durotaxis, or movement in response to surface stiffness, and how this shapes migration and metastasis.
- Define how MICAL2-related signaling from cancer cells and surrounding stromal cells reshapes the tumor microenvironment to support pancreatic cancer invasion.
More about the research
Advanced tumors rarely respond to therapy, so progress depends on understanding how the disease starts and how it spreads. Both projects center on MICAL2, a gene the lab found by comparing super-enhancers in normal pancreas and PDAC. Super-enhancers are DNA stretches that strongly switch on the genes that define a cell's identity. MICAL2 makes an enzyme that takes apart actin filaments, the protein cables that shape cells and let them move. It also turns on genes through serum response factor (SRF), a protein that controls which genes are switched on. One project asks how MICAL2 helps tumors begin. The other asks how it helps cancer cells migrate and spread.
Why it matters
Pancreatic cancer is rarely caught early and resists treatment, and it hits African American and Hispanic patients especially hard. By showing how MICAL2 drives the first steps of tumor formation and the spread of cancer cells, this work could establish MICAL2 as a target for intercepting the disease early or blocking metastasis. It could also clarify when targeting MICAL2 would be most useful. No highly specific MICAL2 inhibitors exist yet.
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.
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.
Saunjoo Yoon
University of Florida, FL·Pharmacology
Test the effectiveness of 4NSGnpcetu, anti-EGFR antibody-coated nanoparticles carrying a modified gemcitabine, in patient-derived pancreatic cancer organoids with stroma and in primary tumor cells from patients.
The school
University of California-San Diego: 84 labs on PI Pages, $1.9B a year on research, 637 research doctorates a year.
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