Dr. Weike Pei obtained his Ph.D. in Immunology at Heidelberg University in 2018. In graduate school, he worked with Dr. Hans-Reimer Rodewald on cell fate decision of hematopoietic stem cells. Following postdoctoral training at the German Cancer Research Center, he joined Harvard Medical School/Brigham and Women’s Hospital as a Research Fellow, working on immune regulation and cancer immunotherapy. His research is published in Nature, Cell Stem Cell, Nature Protocols, Cell Research and other journals. In 2022, Dr. Weike Pei joined Westlake University as an Assistant Professor.

The development of blood and immune system starts from hematopoietic stem cells (HSCs), following a series of cell fate decision events, ultimately giving rise to a complex defending system with distinct cell lineages. ‘How cell fate choice is regulated’ is a long-standing question in biology. At the molecular level, transcriptional and epigenetic networks define a specific phenotype of immune cells. At the cellular level, specialized cells integrate extracellular signals to establish stable cell fate. At the multicellular level, cell-cell interactions between tissue and immune cells coordinate and maintain tissue homeostasis.

Our previous research was focused on the development and application of novel lineage tracing technologies for understanding cell fate decision. We developed a barcode-based clonal lineage tracing approach, termed Polylox. Using the Polylox, we discovered that HSCs are comprised of subsets with different fate patterns: multilineage, myeloid-restricted and differentiation-inactive under steady-state (Nature, 2017; Nature Protocols, 2019). To decode the molecular programs that determine HSC fate, we developed the PolyExpress RNA barcoding system that enables paired analysis of cell fate and transcriptomes at single-cell resolution. Applying the PolyExpress, we identified potential HSC fate regulators (e.g. Hoxb2) in situ, providing a new entry point to investigate the molecular mechanism of cell fate choice (Cell Stem Cell, 2020).

By integrating developmental biology, immunology, systems biology and synthetic biology, we are developing multi-dimensional single-cell lineage tracing technologies, which aims to study cell fate regulation at genetic, epigenetic, transcriptional and spatial-temporal scales. Using novel single cell approaches, we will investigate the development and regeneration of the blood and immune system under physiological conditions and challenges such as cancer, viral infection and aging.

Our research centers around the following topics:

(1) establishing next-generation single-cell fate mapping tools

(2) resolving the fate of hematopoietic stem cells in health and aging

(3) optimizing the in vitro differentiation methods of immune cells for cellular therapy (e.g. CAR-NK)

(4) dissecting the response of immune cells (e.g. myeloid cells, T cells, B cells) upon cancer and infection

Additionally, we will investigate cell fate decision and lineage commitment in several solid organs (e.g. embryo, brain, tumor) based on collaboration with other groups. 

1. Pei W*, Feyerabend TB*, Rossler J, Wang X, Postrach D, Busch K, Rode I, Klapproth K, Dietlein N, Quedenau C, Chen W, Sauer S, Wolf S, Hofer T, Rodewald HR. Polylox barcoding reveals haematopoietic stem cell fates realized in vivo. Nature. 2017; 548: 456-460.

(Featured in Nature Methods, Elected by Faculty of 1000)

2. Pei W*, Shang F*, Wang X*, Fanti AK, Greco A, Busch K, Klapproth K, Qin Zhang, Quedenau C, Sauer S, Feyerabend TB, Hofer T, Rodewald HR. Resolving fates and single-cell transcriptomes of hematopoietic stem cell clones by PolyloxExpress barcoding. Cell Stem Cell. 2020; 27: 383-395. Cover Article, Preview feature in Cell Stem Cell.

(Cover Article, Preview feature in Cell Stem Cell)

3. Pei W*, Wang X*, Rossler J*, Feyerabend TB, Hofer T, Rodewald HR. Using Cre-recombinase-driven Polylox barcoding for in vivo fate mapping in mice. Nature Protocols. 2019; 14: 1820-1840.

4. Pei W^#, Kuchroo VK^#. tRNA-m¹A modification: a translational checkpoint for T cell expansion. Cell Research. (In press)

5. Rodewald HR, Feyerabend TB, Pei W. Genetic random DNA barcode generator for in vivo cell tracing. PCT/EP2016/065932.  

Email: peiweike@westlake.edu.cn

We have several open positions for staff scientists, postdoctoral fellows, graduate students, research assistants and interns. We aim to create an encouraging environment for all lab members to pursue original studies ranging from technology development, target discovery to translation research. All applicants with strong passion in our research are warmly welcomed to join us!