Xiancai Zhong

• Doctor of Philosophy
• City of Hope National Medical Center

Recurrent somatic mutations in spliceosome factor 3b subunit 1 (SF3B1) are identified in hematopoietic malignancies, with SF3B1-K700E being the most common one. Here, we show that regulatory T cell (T reg )–specific expression of SF3B1-K700E ( Sf3b1 K700Efl/+ /Foxp3 YFP-Cre ) results in spontaneous autoimmune phenotypes. CD4 ⁺ T cells from Sf3b1 K7...

Th17 cells are a subset of IL-17-expressing CD4+ T helper cells and play a predominant role in the pathogenesis of autoimmune diseases such as multiple sclerosis and psoriasis. Th17 cells sustain their activation and effector functions primarily through a metabolic profile characterized by high glycolytic and oxidative metabolism. Both glycolysis a...

Steroid receptor coactivator (SRC) family members (SRC1, SRC2 and SRC3) are transcriptional co-regulators. SRCs orchestrate gene transcription by inducing transactivation of nuclear receptors and other transcription factors. Overexpression of SRCs is widely implicated in a range of cancers, especially hormone-related cancers. As coactivators, SRCs...

Nuclear receptor coactivator 2 (Ncoa2) is a member of the Ncoa family of co-activators, and we previously showed that Ncoa2 regulates the differentiation of induced regulatory T cells. However, it remains unknown if Ncoa2 plays a role in CD8+ T-cell function. Here, we show that Ncoa2 promotes CD8+ T cell-mediated immune responses against tumors by...

T cell activation stimulates substantially increased protein synthesis activity to accumulate sufficient biomass for cell proliferation. The protein synthesis is fueled by the amino acids transported from the environment. Steroid nuclear receptor coactivator 2 (SRC2) is a member of a family of transcription coactivators. Here, we show that SRC2 rec...

RORγt is known to instruct the differentiation of T helper 17 (T H 17) cells that mediate the pathogenesis of autoimmune diseases. However, it remains unknown whether RORγt plays a distinct role in the differentiation and effector function of T H 17 cells. Here, we show that mutation of RORγt lysine-256, a ubiquitination site, to arginine (K256R) s...

Rationale: Immunosuppression in the tumor microenvironment (TME) is key to the pathogenesis of solid tumors. Tumor cell-intrinsic autophagy is critical for sustaining both tumor cell metabolism and survival. However, the role of autophagy in the host immune system that allows cancer cells to escape immune destruction remains poorly understood. Here...

Steroid nuclear receptor coactivator 2 (SRC2) is a member of a family of transcription coactivators. While SRC1 inhibits the differentiation of regulatory T cells (Tregs) critical for establishing immune tolerance, we show here that SRC2 stimulates Treg differentiation. SRC2 is dispensable for the development of thymic Tregs, whereas naive CD4+ T c...

Rationale Immunosuppression in the tumor microenvironment (TME) is key to the pathogenesis of solid tumors. Tumor cell-intrinsic autophagy is critical for sustaining both tumor cell metabolism and survival. However, the role of autophagy in the host immune system that allows cancer cells to escape immune destruction remains poorly understood. Here,...

Macrophages are essential in eliciting antibody-dependent cellular phagocytosis (ADCP) of cancer cells. However, a satisfactory anticancer efficacy of ADCP is contingent on early antibody administration, and resistance develops along with cancer progression. Here, we investigate the mechanisms underlying ADCP and demonstrate an effective combinator...

Tumor-associated macrophages (TAMs) are often the most abundant immune cells in the tumor microenvironment (TME). Strategies targeting TAMs to enable tumor cell killing through cellular phagocytosis have emerged as promising cancer immunotherapy. While several phagocytosis checkpoints have been identified, the desired efficacy has not yet been achi...

Peptidyl‐prolyl cis‐trans isomerase NIMA‐interacting 1 (Pin1) has been frequently overexpressed in many types of malignancy, suggesting its oncogenic function. It recognizes phosphorylated serine or threonine (pSer/Thr) of a target protein and isomerizes the adjacent proline (Pro) residue, thereby altering folding, subcellular localization, stabili...

While failure in resolution of inflammation is considered to increase the risk of tumorigenesis, there is paucity of experimental as well as clinical evidence supporting this association. Resolvin D1 (RvD1) is a representative pro‐resolving lipid mediator that is endogenously generated from docosahexaenoic acid for the resolution of inflammation. H...

Tumor-associated macrophages (TAMs) represent one of the most abundant components of the tumor microenvironment and play important roles in tumor development and progression. TAMs display plasticity and functional heterogeneity as reflected by distinct phenotypic subsets. TAMs with an M1 phenotype have proinflammatory and anti-tumoral properties wh...

Uncontrolled macrophage functions cause failure to resolve gut inflammation and has been implicated in the pathogenesis of inflammatory bowel disease (IBD). 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), one of endogenous lipid mediators formed from arachidonic acid during the inflammatory process, has been reported to terminate inflammation. However...

Chemotherapy is commonly used as a major therapeutic option for breast cancer treatment, but its efficacy is often diminished by disruption of patient’s anti-tumor immunity. Chemotherapy-generated tumor cell debris could hijack accumulated tumor-associated macrophages (TAMs), provoking tumor recurrence. Therefore, reprogramming TAMs to acquire an i...

Korean Red Ginseng (KRG) exerts chemopreventive effects on experimentally induced carcinogenesis through multiple mechanisms. In this study, we investigated effects of KRG on dextran sulfate sodium (DSS)-induced colitis and azoxymethane (AOM) plus DSS-induced colon carcinogenesis in mice. Male C57BL/6 J mice were fed diet containing 1% KRG or a sta...

Prostaglandin E2 (PGE2) plays a key role in inflammation-associated carcinogenesis. NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the oxidation of the 15(S)-hydroxyl group of PGE2 to generate 15-keto PGE2. 15-PGDH has been known as a tumor suppressor in various malignancies including colon cancer. However, the molecular m...

Background: Baicalein is a bioactive flavone that is originally extracted from the root of Scutellaria baicalensis Georgi. This plant has long served as Chinese herbal medicine in the management of multiple diseases including inflammatory bowel diseases. Although it has been revealed that baicalein inhibits experimental colitis in mice, the molecu...

One of the most common treatment options for cancer is a chemotherapy. After chemotherapy, however, unwanted host effects provoke tumor recurrence and aggressiveness of cancer cells, which often arise as a consequence of disruption in the patient's immune system. Lymphocytes, such as CD8⁺ cytotoxic T lymphocytes (CTLs), which have capability of sup...

A key event required for effective resolution of inflammation is efferocytosis, which is defined as phagocytic removal of apoptotic cells mostly by macrophages acquiring an alternatively activated phenotype (M2). c-Myc has been reported to play a role in alternative activation of human macrophages and is proposed as one of the M2 macrophage markers...

Background Curcumin, a yellow ingredient of turmeric (Curcuma longa Linn, Zingiberaceae), has long been used in traditional folk medicine in the management of inflammatory disorders. Although curcumin has been reported to inhibit experimentally-induced colitis and carcinogenesis, the underlying molecular mechanisms remain largely unresolved. Metho...

Inflammatory bowel diseases, including ulcerative colitis and Crohn's disease, are persistent disorders that lead to development of colitis-associated cancer (CAC). Seeking the resolution of colitis has been addressed as a new therapeutic strategy to CAC. Resolvin D1 (RvD1) is an endogenous lipid mediator that is generated from docosahexaenoic acid...

Resolution of inflammation that occurs after microbial infection or tissue damage is an important physiologic process in maintaining or restoring host homeostasis. Taurine chloramine (TauCl) is formed by a reaction between taurine and hypochlorite in leukocytes, and it is especially abundant in activated neutrophils that encounter an oxidative burs...

Perilla frutescens is a culinary and medicinal herb which has a strong anti-inflammatory and antioxidative effects. In the present study, we investigated the effects of Perilla frutescens extract (PE) against dextran sulfate sodium (DSS)-induced mouse colitis, an animal model that mimics human inflammatory bowel disease (IBD). Five-week-old male IC...

Resolution of inflammation is an active process which is important for maintaining or restoring homeostasis in response to inflammatory insult. Failure in resolution results in persistent and chronic inflammation which increases the risk of cancer development. Efferocytosis, an essential part of resolution of inflammation, is defined as phagocytic...

Helicobacter pylori (H. pylori) infection has been known to be implicated in human gastric carcinogenesis. Snail, the zinc-finger transcription factor known as a key inducer of changes in the cell shape and morphogenetic movement, is aberrantly overexpressed and correlates with lymph node metastasis in gastric cancer. In the present study, we inves...

Turmeric (Curcuma longa L., Zingiberaceae) has a long history of use in medicine for the treatment of inflammatory conditions. One of the major constituents of turmeric is curcumin (diferuloylmethane), which is responsible for its characteristic yellow color. In the present study, we have examined the chemoprotective effects of curcuminon dextran s...

Aims: To evaluate the effects of oligonol administration on experimentally induced colitis and colonic adenoma formation. Results: Oral administration of oligonol protected against mouse colitis induced by dextran sulfate sodium (DSS). Under the same experimental conditions, oligonol administration significantly inhibited the activation of nucle...