E proteins have been shown to play an important role during various stages of B and T cell development. E proteins execute this regulatory function mainly via binding to the E-box sequence around the target genes. However, the activity of E proteins can be inhibited by Id proteins, such as Id2 and Id3 in the immune system.

Previous studies have suggested crucial roles played by Id2 and Id3 in the differentiation process of certain T cell lineages. Id2 was required for CD8 T cell differentiation and activation, while Id3 was required to inhibit E2A activity upon pre-TCR and TCR signaling. During my PhD study, I performed a wide array of experiments to probe into the functions of Id2 and Id3 during the development of regulatory T cells (Treg) and innate-like follicular helper T (Tfh) cells. My work helped unveil that Id2 and Id3 expression was required for Treg cells to suppress the onset of fatal Th2-mediated inflammation. Meanwhile, I also discovered that thymic Id2 and Id3 expression was indispensable for inhibiting the expansion of innate-like Tfh cells and the pathogenesis of αβ T cell lymphoma.

Besides T cells, B cells are also a target population to be regulated by Id proteins like Id3. Ablating Id3 expression specifically in the B cells, I found that these Id3-deficient B cells were clearly impaired in their ability to differentiate into germinal centers upon antigen stimulation. In addition, without Id3 expression, these B cells can no longer elicit any IgG1 response during the memory phase upon encountering a secondary challenge.

To summarize, my PhD study helped to reveal the important functions played by Id2 and Id3 during the differentiation and activation of different lymphocytes.

In 2010, the famous writer Fei Dao called Chinese science fiction “a lonely hidden army,” emphasizing both its marginalized position and its power to contend with the state. Ten years later, Jing Tsu described science fiction as the “secret weapon in China’s soft-power arsenal,” drawing attention to the “grassroots fan base” and its enthusiasm about the genre. These changing metaphors indicate the potential significance of reading Chinese science fiction not just as a literary genre, but participatory culture. Taking Remembrance of Earth’s Past trilogy as an example, this thesis gives a chronological review of the development of the Chinese science fiction fandom, and close-reading of the original work and selected fan productions. Through positioning colonial inferiority, state censorship, and gender bias in the frame of fandom, this thesis argues that Chinese science fiction and its fandom together form a space for fans’ reimagination, reinvention and resistance that yields alternative historiographies of China.

Hepatocellular Carcinoma is a complex cancer with little available targeted therapeutics, in part due to the recently uncovered paradoxical roles of previously defined proto-oncogenes. Our lab and others have identified overexpression and ablation of several proto-oncogenes sensitizes the liver towards HCC development. Previously, our lab demonstrated hepatocyte deletion of Shp2/Ptpn11 in mice (SKO) ablates HCC driven by cMET/Δ90-β-catenin or cMET/PIK3CA mutant yet greatly accelerates chemical carcinogen-induced HCC. To clarify the complex mechanisms of Shp2 function in HCC, we examined the contribution of the proto-oncogene Myc, which acts downstream of Shp2. The aim of my dissertation research is to elucidate the novel murine model of Myc-driven tumorigenesis in SKO background, examining cell-intrinsicand extrinsic factors driving tumor development. Original work in this dissertation shows that Myc-driven hepatocellular carcinoma (HCC) is dramatically aggravated in mice with hepatocyte-specific Ptpn11/Shp2 deletion. Using single-cell RNA-sequencing coupled with functional assays, we show Shp2-knockout livers exhibit defective clearance of tumor-initiating cells by altering macrophage polarization and reducing macrophage phagocytic activity, resulting in an immune-suppressive environment. We uncover that Myc-induced tumors selectively develop from the rare Shp2-positive hepatocytes in Shp2-deficent liver. Myc-driven oncogenesis depends on intact Ras-Erk signaling, driven by Shp2, to sustain Myc stability. Basal Wnt/β-catenin signaling is upregulated in Shp2-deficient liver, which is further augmented by Myc transfection. Ablating Ctnnb1 suppresses Myc-induced HCC in Shp2-deficient livers, revealing an essential role of β- catenin in assisting in Myc-driven HCC. Consistently, Myc overexpression and CTNNB1 mutations are frequently co-detected in HCC patients with poor prognosis. Single cell RNA sequencing and functional in vivo / in vitro data together reveal the complex mechanisms of liver tumorigenesis driven by cell-intrinsic oncogenic signaling of Myc, supported by intrinsic Shp2 and β-catenin signaling, in cooperation with a tumor promoting microenvironment generated by disruption of Shp2 proto-oncogenic signaling.