Yan Li
Case Western Reserve University, OH·Genetics
Insulin-making beta cells in the pancreas keep blood sugar in check, and their loss or failure causes diabetes. Two connected questions run through this work.
- Fields
Genetics
Biology
Medicine & Clinical Research
- Topics
pancreatic beta cells
β-cells
diabetes
- Grants
- 2 known grants, through Jun 2028
What they work on
- Map how gene activity changes, cell by cell, as 24 human pluripotent stem cell lines become beta cells, using pooled single-cell RNA sequencing that sorts cells back to their line of origin.
- Chart changes in open chromatin with scATAC-seq and in 3D genome folding with low-input Hi-C during beta-cell differentiation, to find the DNA control regions that set cell fate.
- Discover and validate genes and enhancers (DNA switches) that control beta-cell differentiation, using high-throughput CRISPR screens and targeted genome editing.
- Compare beta cells with high and low levels of HNF1A, a gene-switching protein mutated in MODY3 diabetes, using a new single-cell multiome integration strategy.
- Test how HNF1A dosage shapes beta-cell function by raising or lowering it in stem cell-derived beta cells, including its control of FXYD2 and sodium currents.
- Identify upstream regulators of HNF1A in beta cells through genetic and chemical screens in a newly built cell line model.
More about the research
The first is how to reliably grow working beta cells from human pluripotent stem cells, which can turn into any cell type, for research and possible transplantation. The second is why beta cells within one person differ from each other, and whether those differences raise diabetes risk.
Why it matters
People with diabetes, including type 2 diabetes and the inherited form MODY3, could eventually benefit if lab-grown beta cells become consistent enough for transplantation. A clearer map of what controls beta-cell growth from stem cells could make those cells more reliable. Learning how HNF1A shapes differences between beta cells may explain part of diabetes risk and could point to new therapeutic opportunities.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Rafael Arrojo E Drigo
Vanderbilt University, TN·Physiology
Determine how calorie restriction, high-fat diet, aging and ER stress change beta cell epigenetic marks, gene activity, function and lifespan, using single-cell multiome sequencing and in vivo function measurements.
Sushmita Roy
University of Wisconsin-Madison, WI·Computer Science
Develop machine-learning methods, including probabilistic graphical models and matrix factorization, that define cell types and their lineage relationships across species from scRNA-seq and scATAC-seq while modeling the species phylogeny.
Xiangming Ji
Pennsylvania State University, PA·Physiology
Determine how metallothionein 1E (MT1E), a metal-binding protein that buffers oxidative stress, affects the function and survival of insulin-producing beta cells during the development of cystic fibrosis-related diabetes.
The school
Case Western Reserve University: 34 labs on PI Pages, $643M a year on research, 213 research doctorates a year.
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