Honors & Awards


  • Justice, Diversity, Equity & Inclusion Seed Grants in Radiology, Stanford University (2021-2022)
  • The National Scholarship, Ministry of Education of the People's Republic of China (2010-2012)
  • “Excellent graduates of Hunan” Award, Department of Education of Hunan province, China (2012)
  • Top Prize in the All China Medical Student Clinical skill competition, Department of Higher Education of Ministry of education (2012)
  • “The best contestant” award in the All China Medical Student Clinical skill competition, Department of Higher Education of Ministry of education (2012)
  • Joint PhD Student Scholarship, China Scholarship Council (2014-2016)

Professional Education


  • Joint PhD student, University of Miami, Surgery (2016)
  • Bachelor of Medicine, Central South University (2013)
  • Doctor of Philosophy, Peking University (2017)

All Publications


  • Discovery of CASP8 as a potential biomarker for high-risk prostate cancer through a high-multiplex immunoassay. Scientific reports Liu, S. n., Garcia-Marques, F. n., Zhang, C. A., Lee, J. J., Nolley, R. n., Shen, M. n., Hsu, E. C., Aslan, M. n., Koul, K. n., Pitteri, S. J., Brooks, J. D., Stoyanova, T. n. 2021; 11 (1): 7612

    Abstract

    Prostate cancer remains the most common non-cutaneous malignancy among men in the United States. To discover potential serum-based biomarkers for high-risk prostate cancer, we performed a high-multiplex immunoassay utilizing patient-matched pre-operative and post-operative serum samples from ten men with high-grade and high-volume prostate cancer. Our study identified six (CASP8, MSLN, FGFBP1, ICOSLG, TIE2 and S100A4) out of 174 proteins that were significantly decreased after radical prostatectomy. High levels of CASP8 were detected in pre-operative serum samples when compared to post-operative serum samples and serum samples from patients with benign prostate hyperplasia (BPH). By immunohistochemistry, CASP8 protein was expressed at higher levels in prostate cancer tissues compared to non-cancerous and BPH tissues. Likewise, CASP8 mRNA expression was significantly upregulated in prostate cancer when compared to benign prostate tissues in four independent clinical datasets. In addition, mRNA levels of CASP8 were higher in patients with recurrent prostate cancer when compared to patients with non-recurrent prostate cancer and high expression of CASP8 was associated with worse disease-free survival and overall survival in renal cancer. Together, our results suggest that CASP8 may potentially serve as a biomarker for high-risk prostate cancer and possibly renal cancer.

    View details for DOI 10.1038/s41598-021-87155-5

    View details for PubMedID 33828176

  • Discovery of PTN as a serum-based biomarker of pro-metastatic prostate cancer. British journal of cancer Liu, S. n., Shen, M. n., Hsu, E. C., Zhang, C. A., Garcia-Marques, F. n., Nolley, R. n., Koul, K. n., Rice, M. A., Aslan, M. n., Pitteri, S. J., Massie, C. n., George, A. n., Brooks, J. D., Gnanapragasam, V. J., Stoyanova, T. n. 2020

    Abstract

    Distinguishing clinically significant from indolent prostate cancer (PC) is a major clinical challenge. We utilised targeted protein biomarker discovery approach to identify biomarkers specific for pro-metastatic PC. Serum samples from the cancer-free group; Cambridge Prognostic Group 1 (CPG1, low risk); CPG5 (high risk) and metastatic disease were analysed using Olink Proteomics panels. Tissue validation was performed by immunohistochemistry in a radical prostatectomy cohort (n = 234). We discovered that nine proteins (pleiotrophin (PTN), MK, PVRL4, EPHA2, TFPI-2, hK11, SYND1, ANGPT2, and hK14) were elevated in metastatic PC patients when compared to other groups. PTN levels were increased in serum from men with CPG5 compared to benign and CPG1. High tissue PTN level was an independent predictor of biochemical recurrence and metastatic progression in low- and intermediate-grade disease. These findings suggest that PTN may represent a novel biomarker for the presence of poor prognosis local disease with the potential to metastasise warranting further investigation.

    View details for DOI 10.1038/s41416-020-01200-0

    View details for PubMedID 33288843

  • Trop2 is a driver of metastatic prostate cancer with neuroendocrine phenotype via PARP1. Proceedings of the National Academy of Sciences of the United States of America Hsu, E. C., Rice, M. A., Bermudez, A. n., Marques, F. J., Aslan, M. n., Liu, S. n., Ghoochani, A. n., Zhang, C. A., Chen, Y. S., Zlitni, A. n., Kumar, S. n., Nolley, R. n., Habte, F. n., Shen, M. n., Koul, K. n., Peehl, D. M., Zoubeidi, A. n., Gambhir, S. S., Kunder, C. A., Pitteri, S. J., Brooks, J. D., Stoyanova, T. n. 2020

    Abstract

    Resistance to androgen deprivation therapy, or castration-resistant prostate cancer (CRPC), is often accompanied by metastasis and is currently the ultimate cause of prostate cancer-associated deaths in men. Recently, secondary hormonal therapies have led to an increase of neuroendocrine prostate cancer (NEPC), a highly aggressive variant of CRPC. Here, we identify that high levels of cell surface receptor Trop2 are predictive of recurrence of localized prostate cancer. Moreover, Trop2 is significantly elevated in CRPC and NEPC, drives prostate cancer growth, and induces neuroendocrine phenotype. Overexpression of Trop2 induces tumor growth and metastasis while loss of Trop2 suppresses these abilities in vivo. Trop2-driven NEPC displays a significant up-regulation of PARP1, and PARP inhibitors significantly delay tumor growth and metastatic colonization and reverse neuroendocrine features in Trop2-driven NEPC. Our findings establish Trop2 as a driver and therapeutic target for metastatic prostate cancer with neuroendocrine phenotype and suggest that high Trop2 levels could identify cancers that are sensitive to Trop2-targeting therapies and PARP1 inhibition.

    View details for DOI 10.1073/pnas.1905384117

    View details for PubMedID 31932422

  • Gata3 restrains B cell proliferation and cooperates with p18(INK4c) to repress B cell lymphomagenesis ONCOTARGET Liu, S., Chan, H., Bai, F., Ma, J., Scott, A., Robbins, D. J., Capobianco, A. J., Zhu, P., Pei, X. 2016; 7 (39): 64007–20

    Abstract

    GATA3, a lineage specifier, controls lymphoid cell differentiation and its function in T cell commitment and development has been extensively studied. GATA3 promotes T cell specification by repressing B cell potential in pro T cells and decreased GATA3 expression is essential for early B cell commitment. Inherited genetic variation in GATA3 has been associated with lymphoma susceptibility. However, it remains elusive how the loss of function of GATA3 promotes B cell development and induces B cell lymphomas. In this study, we found that haploid loss of Gata3 by heterozygous germline deletion increased B cell populations in the bone marrow (BM) and spleen, and decreased CD4 T cell populations in the thymus, confirming that Gata3 promotes T and suppresses B cell development. We discovered that haploid loss of Gata3 reduced thymocyte proliferation with induction of p18Ink4c (p18), an inhibitor of CDK4 and CDK6, but enhanced B cell proliferation in the BM and spleen independent of p18. Loss of p18 partially restored Gata3 deficient thymocyte proliferation, but further stimulated Gata3 deficient B cell proliferation in the BM and spleen. Furthermore, we discovered that haploid loss of Gata3 in p18 deficient mice led to the development of B cell lymphomas that were capable of rapidly regenerating tumors when transplanted into immunocompromised mice. These results indicate that Gata3 deficiency promotes B cell differentiation and proliferation, and cooperates with p18 loss to induce B cell lymphomas. This study, for the first time, reveals that Gata3 is a tumor suppressor specifically in B cell lymphomagenesis.

    View details for DOI 10.18632/oncotarget.11746

    View details for Web of Science ID 000387167800094

    View details for PubMedID 27588406

    View details for PubMedCentralID PMC5325421

  • PDGFRβ is an essential therapeutic target for BRCA1-deficient mammary tumors. Breast cancer research : BCR Bai, F. n., Liu, S. n., Liu, X. n., Hollern, D. P., Scott, A. n., Wang, C. n., Zhang, L. n., Fan, C. n., Fu, L. n., Perou, C. M., Zhu, W. G., Pei, X. H. 2021; 23 (1): 10

    Abstract

    Basal-like breast cancers (BLBCs) are a leading cause of cancer death due to their capacity to metastasize and lack of effective therapies. More than half of BLBCs have a dysfunctional BRCA1. Although most BRCA1-deficient cancers respond to DNA-damaging agents, resistance and tumor recurrence remain a challenge to survival outcomes for BLBC patients. Additional therapies targeting the pathways aberrantly activated by BRCA1 deficiency are urgently needed.Most BRCA1-deficient BLBCs carry a dysfunctional INK4-RB pathway. Thus, we created genetically engineered mice with Brca1 loss and deletion of p16INK4A, or separately p18INK4C, to model the deficient INK4-RB signaling in human BLBC. By using these mutant mice and human BRCA1-deficient and proficient breast cancer tissues and cells, we tested if there exists a druggable target in BRCA1-deficient breast cancers.Heterozygous germline or epithelium-specific deletion of Brca1 in p18INK4C- or p16INK4A-deficient mice activated Pdgfrβ signaling, induced epithelial-to-mesenchymal transition, and led to BLBCs. Confirming this role, targeted deletion of Pdgfrβ in Brca1-deficient tumor cells promoted cell death, induced mesenchymal-to-epithelial transition, and suppressed tumorigenesis. Importantly, we also found that pharmaceutical inhibition of Pdgfrβ and its downstream target Pkcα suppressed Brca1-deficient tumor initiation and progression and effectively killed BRCA1-deficient cancer cells.Our work offers the first genetic and biochemical evidence that PDGFRβ-PKCα signaling is repressed by BRCA1, which establishes PDGFRβ-PKCα signaling as a therapeutic target for BRCA1-deficient breast cancers.

    View details for DOI 10.1186/s13058-021-01387-x

    View details for PubMedID 33478572

    View details for PubMedCentralID PMC7819225

  • MCM2-7 complex is a novel druggable target for neuroendocrine prostate cancer. Scientific reports Hsu, E. C., Shen, M., Aslan, M., Liu, S., Kumar, M., Garcia-Marques, F., Nguyen, H. M., Nolley, R., Pitteri, S. J., Corey, E., Brooks, J. D., Stoyanova, T. 2021; 11 (1): 13305

    Abstract

    Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer that rarely develops de novo in primary tumors and is commonly acquired during the development of treatment resistance. NEPC is characterized by gain of neuroendocrine markers and loss of androgen receptor (AR), making it resistant to current therapeutic strategies targeting the AR signaling axis. Here, we report that MCM2, MCM3, MCM4, and MCM6 (MCM2/3/4/6) are elevated in human NEPC and high levels of MCM2/3/4/6 are associated with liver metastasis and poor survival in prostate cancer patients. MCM2/3/4/6 are four out of six proteins that form a core DNA helicase (MCM2-7) responsible for unwinding DNA forks during DNA replication. Inhibition of MCM2-7 by treatment with ciprofloxacin inhibits NEPC cell proliferation and migration in vitro, significantly delays NEPC tumor xenograft growth, and partially reverses the neuroendocrine phenotype in vivo. Our study reveals the clinical relevance of MCM2/3/4/6 proteins in NEPC and suggests that inhibition of MCM2-7 may represent a new therapeutic strategy for NEPC.

    View details for DOI 10.1038/s41598-021-92552-x

    View details for PubMedID 34172788

  • The role of Trop2 in prostate cancer: an oncogene, biomarker, and therapeutic target. American journal of clinical and experimental urology Shen, M. n., Liu, S. n., Stoyanova, T. n. 2021; 9 (1): 73–87

    Abstract

    Prostate cancer remains the second leading cause of cancer-associated deaths amongst American men. Trop2, a cell surface glycoprotein, correlates with poor clinical outcome and is highly expressed in metastatic, treatment-resistant prostate cancer. High levels of Trop2 are prognostic for biochemical recurrence. Trop2 regulates tumor growth and metastatic ability of prostate cancer. Moreover, overexpression of Trop2 drives the transdifferentiation to neuroendocrine phenotype in prostate cancer. In addition, Trop2 is overexpressed across epithelial cancers and has emerged as a promising therapeutic target in various solid epithelial cancers. The FDA (Food and Drug Administration) recently approved the use of a Trop2-targeting ADC (antibody-drug conjugate), Sacituzumab Govitecan (IMMU-132), for metastatic, triple-negative breast cancer with at least two prior therapies. Here, we review the role of Trop2 in prostate tumorigenesis and its potential as a promising biomarker and therapeutic target for prostate cancer.

    View details for PubMedID 33816696

    View details for PubMedCentralID PMC8012837

  • Plectin is a regulator of prostate cancer growth and metastasis. Oncogene Buckup, M., Rice, M. A., Hsu, E., Garcia-Marques, F., Liu, S., Aslan, M., Bermudez, A., Huang, J., Pitteri, S. J., Stoyanova, T. 2020

    Abstract

    Prostate cancer is responsible for over 30,000 US deaths annually, attributed largely to incurable metastatic disease. Here, we demonstrate that high levels of plectin are associated with localized and metastatic human prostate cancer when compared to benign prostate tissues. Knock-down of plectin inhibits prostate cancer cell growth and colony formation in vitro, and growth of prostate cancer xenografts in vivo. Plectin knock-down further impairs aggressive and invasive cellular behavior assessed by migration, invasion, and wound healing in vitro. Consistently, plectin knock-down cells have impaired metastatic colonization to distant sites including liver, lung, kidney, bone, and genitourinary system. Plectin knock-down inhibited number of metastases per organ, as well as decreased overall metastatic burden. To gain insights into the role of plectin in prostate cancer growth and metastasis, we performed proteomic analysis of prostate cancer plectin knock-down xenograft tissues. Gene set enrichment analysis shows an increase in levels of proteins involved with extracellular matrix and laminin interactions, and a decrease in levels of proteins regulating amino acid metabolism, cytoskeletal proteins, and cellular response to stress. Collectively these findings demonstrate that plectin is an important regulator of prostate cancer cell growth and metastasis.

    View details for DOI 10.1038/s41388-020-01557-9

    View details for PubMedID 33219316

  • LncRNA GNAS-AS1 facilitates ER+ breast cancer cells progression by promoting M2 macrophage polarization via regulating miR-433-3p/GATA3 axis. Bioscience reports Liu, S. Q., Zhou, Z. Y., Dong, X. n., Guo, L. n., Zhang, K. J. 2020; 40 (7)

    Abstract

    ER+ breast cancer is the most common type of breast cancer, which seriously affects the physical and mental health of women. Recently, lncRNAs mediated tumor-associated macrophages (TAM) were identified to involve in tumorigenesis. Therefore, the present study aimed at demonstrating the regulatory network of GNAS-AS1 in TAM-mediated ER+ breast cancer progress.The expression levels of genes were evaluated using qRT-PCR. The proportions of polarized macrophages (M1, M2) were assessed by flow cytometry. Cell proliferation, migration and invasion were evaluated by CCK-8, wound healing and transwell assay, respectively. Double-luciferase reporter system was used to detect the interaction between molecules. Western blot was applied to test protein levels.The expression of GNAS-AS1 was obviously increased in ER+ breast cancer tissues and cell lines, as well as M2 macrophages. GNAS-AS1 facilitated the capabilities of proliferation, migration and invasion of ER+ breast cancer cells by accelerating M2 macrophage polarization via directly sponging miR-433-3p. GATA3, as a target of miR-433-3p, could positively regulate by GNAS-AS1. Furthermore, either miR-433-3p overexpression or GATA3 knockdown impaired the effects of GNAS-AS1 on M2 macrophage polarization and ER+ breast cancer cells progression.GNAS-AS1/miR-433-3p/GATA3 axis promoted proliferation, metastasis of ER+ breast cancer cells by accelerating M2 macrophage polarization. The mechanism may provide a new strategy and target for ER+ breast cancer treatment.

    View details for DOI 10.1042/BSR20200626

    View details for PubMedID 32538432

    View details for PubMedCentralID PMC7327181

  • A specific immune tolerance toward offspring cells is to exist after the mother lymphocyte infusion IMMUNOBIOLOGY Xing, H., Liu, S., Chen, X., Fang, F., Wu, X., Zhu, P. 2017; 222 (4): 658–63

    Abstract

    To examine immune tolerance between maternal lymphocytes and offspring tissue after a donor lymphocyte infusion.Mouse models were established by mating female BALB/c mice with male C57BL mice. Splenic lymphocytes from donors of different genetic backgrounds were labeled with carboxyfluorescein succinimidyl ester (CFSE), and 1×107 of the labeled cells were intravenously injected into a recipient. At 6h, 24h, 72h and 120h after the infusion, mononuclear cells in recipient spleen, liver, thymus, lymph nodes, and peripheral blood were collected. CFSE+, CFSE-, CD3+, CD8+, CD4+, CD19+, NK1.1+, CD25+, and CD127+ lymphocytes in those samples were analyzed by flow cytometry. The distribution of donor T cells, B cells, NK cells, helper T cells, cytotoxic T cells, and recipient regulatory T cells in the tissues were then analyzed.Maternal lymphocytes were more likely to survive in offspring. At 120h after infusion, the percentages of maternal cells in the offspring were 0.52±0.11% in lymph nodes, 0.97±0.04% in peripheral blood, and 0.97±0.11% in the spleen. Few donor cells, if any, were detected in these tissues at 120h after aunt to child, father to child, and unrelated allogeneic infusions were performed. The subtype proportion of donor lymphocytes changed significantly in the recipient tissues. Recipient Treg cells increased in the mother to child group, but not in the aunt to child, father to child, and unrelated allogeneic groups, suggesting a decreased cellular immune response to allogeneic cells in the mother to child group. At 120h after the infusion, no donor cells were detected in the recipient livers and thymuses of all groups, implying that donor cells were barely able to colonize in the liver and thymus.Specific immune tolerance to maternal lymphocytes exists in offspring. An infusion of maternal donor lymphocytes may produce a relatively persistent effect of adoptive immunotherapy with reduced side-effects.

    View details for DOI 10.1016/j.imbio.2016.12.003

    View details for Web of Science ID 000396960500008

    View details for PubMedID 28065449

  • p16 loss rescues functional decline of Brca1-deficient mammary stem cells CELL CYCLE Scott, A., Bai, F., Chan, H., Liu, S., Slingerland, J. M., Robbins, D. J., Capobianco, A. J., Pei, X. 2017; 16 (8): 759–64

    Abstract

    Recent evidence indicates that the accumulation of endogenous DNA damage can induce senescence and limit the function of adult stem cells. It remains elusive whether deficiency in DNA damage repair is associated with the functional alteration of mammary stem cells. In this article, we reported that senescence was induced in mammary epithelial cells during aging along with increased expression of p16Ink4a (p16), an inhibitor of CDK4 and CKD6. Loss of p16 abrogated the age-induced senescence in mammary epithelial cells and significantly increased mammary stem cell function. We showed that loss of Brca1, a tumor suppressor that functions in DNA damage repair, in the mammary epithelium induced senescence with induction of p16 and a decline of stem cell function, which was rescued by p16 loss. These data not only answer the question as to whether deficiency in DNA damage repair is associated with the functional decline of mammary stem cells, but also identify the role of p16 in suppressing Brca1-deficient mammary stem cell function.

    View details for DOI 10.1080/15384101.2017.1295185

    View details for Web of Science ID 000399738300011

    View details for PubMedID 28278054

    View details for PubMedCentralID PMC5405722

  • p16(INK4a) suppresses BRCA1-deficient mammary tumorigenesis ONCOTARGET Scott, A., Bai, F., Chan, H., Liu, S., Ma, J., Slingerland, J. M., Robbins, D. J., Capobianco, A. J., Pei, X. 2016; 7 (51): 84496–507

    Abstract

    Senescence prevents the proliferation of genomically damaged, but otherwise replication competent cells at risk of neoplastic transformation. p16INK4A (p16), an inhibitor of CDK4 and CDK6, plays a critical role in controlling cellular senescence in multiple organs. Functional inactivation of p16 by gene mutation and promoter methylation is frequently detected in human breast cancers. However, deleting p16 in mice or targeting DNA methylation within the murine p16 promoter does not result in mammary tumorigenesis. How loss of p16 contributes to mammary tumorigenesis in vivo is not fully understood.In this article, we reported that disruption of Brca1 in the mammary epithelium resulted in premature senescence that was rescued by p16 loss. We found that p16 loss transformed Brca1-deficient mammary epithelial cells and induced mammary tumors, though p16 loss alone was not sufficient to induce mammary tumorigenesis. We demonstrated that loss of both p16 and Brca1 led to metastatic, basal-like, mammary tumors with the induction of EMT and an enrichment of tumor initiating cells. We discovered that promoter methylation silenced p16 expression in most of the tumors developed in mice heterozygous for p16 and lacking Brca1. These data not only identified the function of p16 in suppressing BRCA1-deficient mammary tumorigenesis, but also revealed a collaborative effect of genetic mutation of p16 and epigenetic silencing of its transcription in promoting tumorigenesis. To the best of our knowledge, this is the first genetic evidence directly showing that p16 which is frequently deleted and inactivated in human breast cancers, collaborates with Brca1 controlling mammary tumorigenesis.

    View details for DOI 10.18632/oncotarget.13015

    View details for Web of Science ID 000391353200057

    View details for PubMedID 27811360

    View details for PubMedCentralID PMC5356676

  • Immunophenotypic analysis of abnormal plasma cell clones in bone marrow of primary systemic light chain amyloidosis patients CHINESE MEDICAL JOURNAL Hu Yang, Wang Mangju, Chen Yan, Chen Xue, Fang Fang, Liu Shiqin, Zhang Ying, Wu Xueqiang, Zhu Ping 2014; 127 (15): 2765–70

    Abstract

    Primary systemic light chain amyloidosis (AL) is a rare plasma cell disease, our purpose was to analyze the immunophenotypic characteristics of the plasma cells in bone marrow in AL patients, and explore whether the detection of abnormal plasma cell clones in bone marrow by flow cytometry (FCM) could be used as an important indicator of AL diagnosis.Fresh bone marrow samples were collected from 51 AL, 21 multiple myeloma (MM), and 5 Waldenström's macroglobulinemia (WM) patients. The immunophenotype of bone marrow cells were analyzed and compared by FCM using a panel of antibodies including CD45, CD38, CD138, CD117, CD56, and CD19.In AL, light chain restriction could be identified in 31 cases (60.9%), in which the λ light chain restriction was found in 24 cases (77.4%). In MM, κ light chain restriction was found in 13 cases (61.9%), and λ light chain restriction in eight cases. CD45 on abnormal plasma cells was negative to weakly positive in both AL and MM, but was positive to strongly positive in WM. In the bone marrow plasma cells of the 51 AL, 78.4% were CD56+, 68.6% were CD117+, and 88.2% were CD19-. While in the 21 MM cases, 66.7% were CD56+, 38.1% were CD117+, and 90.4% were CD19-. The plasmacytoid lymphocytes in the five WM patients were CD19+ and CD56-, CD117-.Detection of abnormal plasma cell clones in bone marrow by FCM is valuable for the diagnosis of AL.

    View details for DOI 10.3760/cma.j.issn.0366-6999.20141053

    View details for Web of Science ID 000340691000008

    View details for PubMedID 25146610

  • The Significance Of Abnormal Plasma Cell Clone In Bone Marrow Of Primary Systemic Light Chain Amyloidosis Patients Hu, Y., Wang, M., Chen, Y., Chen, X., Fang, F., Liu Shiqin, Zhang, Y., Wu, X., Zhu, P. AMER SOC HEMATOLOGY. 2013