RESEARCH TOPICS

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Hematopoiesis, Stem Cells, and Immune Responses

One of the biological systems that we utilize is the amazing blood-forming system where blood and immune cell types are generated through the process of hematopoiesis. In a normal adult human being, ~100 to 200 billion new blood cells are generated every day to replace similar numbers of old blood cells. These mature blood cells originate from hematopoietic stem cells and exhibit vastly different forms, shapes and functions, regulating processes such as innate and adaptive immune responses, oxygen transport and coagulation. When the system go awry, malignancy arises in disease forms such as acute myeloid leukemia. We are interested in several questions. What are the functions of special noncoding RNAs (with recent interests on noncoding RNAs present on cell surface) in hematopoietic and immune cells? What regulates the crosstalk between cancer cells and immune cells? What regulates the competition between clones of hematopoietic stem cells? What controls the subcellular organelle shape and function during the differentiation of immune cells?

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Noncoding RNAs

The completion of the human genome project leads to the realization that only a small percentage of our heritable DNA sequences encodes proteins. Instead of being “junk DNA”, a significant portion of the genome is transcribed into the so-called non-coding RNAs.
Our lab is excited about the nascent fields of glycosylated RNAs (or glycoRNAs) and RNAs on the outer cell surface. Most cellular RNAs reside in the cytoplasm and nucleus. However, a fraction of RNAs that contain glycan modification can dwell on the outer cell surface with a long half-life. We recently discovered the first major function of these cell surface glycoRNAs in mediating neutrophil recruitment during inflammation. However, this is only the tip of the iceberg with many open questions that need answers.
Out lab also studies novel molecular functions of a class of small noncoding RNAs unknown as microRNAs (or miRNAs), whose discovery won the Nobel Prize in Physiology or Medicine in 2024. MiRNAs are tiny non-coding RNAs that are ~21 nucleosides in length and are often highly conserved among species. The traditional roles of miRNAs are to downregulate gene expression through recognizing sites in messenger RNAs. Our lab pursues an intriguing angle of identifying non-canonical functions of miRNAs.

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Cancer

Cancer research is a collection of vast fields. There are three angles that we are particularly interested in. First, what molecular processes regulate leukemia initiation and progression? Leukemia itself is a collection of many diseases with diverse genetic changes. We are interested in how noncoding RNAs are affecting leukemia initiation and progression. Second, how do solid cancer cells crosstalk with the immune cells? We are interested in how anti-cancer immunity is regulated by age-associated genetic changes in the hematopoietic stem cells and by chemotherapy drugs. And third, are there new hallmarks of cancer to be discovered? Experimentally, we utilize model systems such as leukemia, colorectal cancer, and melanoma. Computationally, we investigate large datasets for insights into cancer.

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Computational

Computational biology is an integral part of our laboratory. We develop computational tools and pipelines for analyzing data from new technologies. Examples include developing new tools to analyze emerging genomic data types, such as single cell and spatiomics datasets. We also use computation to address biological questions by combining biological instincts with computational expertise. The ever-expanding public datasets can be thoughtfully analyzed to reveal new biological insights, such as on noncoding RNA rules, on cancer principles, and on physiological processes such as aging.