Daniela Sia
Icahn School of Medicine at Mount Sinai, NY·Medicine & Clinical Research
Bile duct cancer that arises inside the liver, called intrahepatic cholangiocarcinoma (iCCA), is one of the hardest cancers to treat: five-year survival is about 5%, over half of cases are found after the tumor has spread, and roughly three in four patients do not respond to the current first-line treatment. Two linked questions drive this work: why do these tumors resist therapy, and what in the tumor's surroundings makes them so hostile to the immune system?
- Fields
Medicine & Clinical Research
Microbiology & Immunology
Genetics
- Topics
intrahepatic cholangiocarcinoma
iCCA
bile duct cancer
- Grants
- 2 known grants, through Apr 2031
What they work on
- Build a biobank of 50 intrahepatic cholangiocarcinoma patient-derived organoids with matched immune and stromal cells from the same patients, and test how faithfully these cultures reproduce the molecular programs of the original tumors.
- Use organoid–immune co-cultures (PDOTs) from 36 patient biopsies taken before standard chemoimmunotherapy to identify why most tumors resist treatment and to design combination regimens that improve response.
- Determine how B7-H4, an immune checkpoint protein overexpressed in most of these tumors, drives cancer cell growth and movement, by manipulating it in human and mouse cell lines and organoids and mapping the proteins its intracellular form binds.
- Test whether B7-H4 shapes the tumor's scar tissue and immune makeup by raising GARP and releasing active TGFβ1, using mouse liver tumors made by hydrodynamic tail vein delivery of Notch1 and Akt1 genes.
- Assess whether combining TGFβ1-blocking drugs with a B7-H4 monoclonal antibody slows tumor growth in genetic and orthotopic mouse models of bile duct cancer.
More about the research
Both projects attack the dense scar-like tissue and immune-suppressive environment that surrounds these tumors, one by building patient-matched laboratory models to test drug combinations, the other by dissecting a specific molecular pathway that appears to build that environment.
Why it matters
Intrahepatic cholangiocarcinoma kills most patients within five years and resists both targeted drugs and immunotherapy. Patient-matched organoid–immune co-cultures could let doctors test combination immunotherapies on a person's own tumor before treating them, and establishing B7-H4 as a driver of the tumor's fibrous, immune-suppressive environment would offer a new drug target that may also apply to other B7-H4-expressing cancers.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Steffi Oesterreich
University of Pittsburgh, PA·Medicine & Clinical Research
Compare ILC cell lines, patient-derived organoids, xenografts, homografts and genetically engineered mice with human ILC tumors using histopathology plus genomic, epigenomic and transcriptomic profiling.
Albert Koong
University of Texas MD Anderson Cancer Center, TX·Medicine & Clinical Research
Identify the HIF2-dependent factor that cancer-associated fibroblasts (CAFs) secrete to push macrophages toward an immune-suppressing M2 state in pancreatic cancer, using mass spectrometry, and determine how it is produced and how it alters macrophages.
Daniel Brat
Northwestern University, IL·Microbiology & Immunology
Test whether the spatial arrangement of tumor-associated macrophages alongside hypoxic glioma cells in the peri-necrotic niche sustains immune suppression, using an RCAS/tv-a mouse model to follow microenvironment changes after necrosis in real time.
The school
Icahn School of Medicine at Mount Sinai: 45 labs on PI Pages, $1.0B a year on research, 62 research doctorates a year.
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