Waihay Wong
Northwestern University, IL·Medicine & Clinical Research·Early-career
As people age, individual blood stem cells pick up mutations, and sometimes one of them outgrows its neighbors so that a sizable fraction of a person's blood cells all carry the same mutation — without any blood cancer being present. This common condition, clonal hematopoiesis of indeterminate potential (CHIP), turns out to be linked to a surprising list of illnesses: cardiovascular disease, chronic obstructive pulmonary disease, chronic liver disease, osteoporosis and gout.
- Fields
Medicine & Clinical Research
Microbiology & Immunology
Genetics
- Topics
clonal hematopoiesis
NLRP3 inflammasome
hematopoietic stem cells
- Grants
- 1 known grant, through Feb 2029
What they work on
- Test whether the NLRP3 inflammasome, an immune-cell sensor that triggers inflammatory signaling, is required for Tet2-deficient blood cells to outcompete normal ones, using mouse models of clonal hematopoiesis, human cell xenografts and patient specimens.
- Define how NLRP3 inflammasome activity changes gene transcription and chromatin accessibility in blood cells, using single-cell sequencing of Tet2-deficient hematopoietic cells.
- Identify which hematopoietic progenitor cell population drives the Tet2-deficient, NLRP3-dependent clonal expansion, by profiling progenitor compartments in clonal hematopoiesis models.
- Evaluate whether the inflammatory drive in clonal hematopoiesis of indeterminate potential (CHIP) can be therapeutically targeted by interfering with NLRP3 inflammasome function.
More about the research
What these conditions share is inflammation, and the genes mutated most often in CHIP — TET2 and DNMT3A, which control how DNA is chemically marked to switch genes on and off — have been tied to excess chemokine production and overactive inflammatory machinery in myeloid immune cells. How that inflammation actually drives the mutant clone to expand, and how it tips some people toward blood cancer, remains unclear.
Why it matters
Clonal hematopoiesis is extremely common with age and raises the risk of heart disease, lung and liver disease, osteoporosis, gout and blood cancers. If the NLRP3 inflammasome proves necessary for mutant blood clones to expand, existing and future anti-inflammatory drugs aimed at this pathway could be tested as a way to slow clonal growth and reduce the downstream disease risk in older adults carrying these mutations.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Britta Will
Albert Einstein College of Medicine, NY·Biology
Map when chaperone-mediated autophagy (CMA), a selective protein-recycling pathway, is active in precancerous CHIP blood stem cells and leukemic stem cells, using a CMA reporter mouse and lentiviral CMA biosensors in patient cells.
Lukasz Gondek
Johns Hopkins University, MD·Medicine & Clinical Research
Determine the cancer-causing potential of donor-derived CHIP in transplant recipients, using a cohort of 1,857 donors over 40 and serial recipient samples to separate true driver mutations from background aging mutations.
Nancy Speck
University of Pennsylvania, PA·Biology
Determine which components of the TGFβ/BMP signaling pathways must be inhibited, and at what time, to improve maturation of SMAD7-deficient pre-HSCs into HSCs, using a quantitative ex vivo culture system with mouse embryo cells.
The school
Northwestern University: 71 labs on PI Pages, $1.3B a year on research, 536 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.