Education

 
 
 
 
 

Doctor of Philosophy in Cancer Biology and Genomics (Bioinformatics)

University of Southern California

Aug 2018 – May 2022 Los Angeles, CA

  • Thesis: Perinatal epigenetic and genetic analyses in childhood cancers
  • Advisors: Dr Joseph L. Wiemels, Dr Adam de Smith
  • Coursework: Human Molecular Genetics, Genetic and Molecular Epidemiology, Principles of Biostatistics, Data Analyses, Machine Learning for the Health Sciences, Analysis of Algorithms
 
 
 
 
 

Bachelor of Medicine (Forensic medicine)

Fudan University

Sep 2009 – Jun 2014 Shanghai, China

  • Coursework: Human Anatomy, Pharmacology, Psychiatry, Radiology, Surgery, Internal Medicine, Pediatrics, Obstetrics and Gynecology

Experience

 
 
 
 
 

Postdoctoral fellow

University of Southern California, Center for Genetic Epidemiology

May 2022 – Nov 2022 Los Angeles, CA

  • Led multiple large scale GWAS and EWAS projects on childhood cancers
  • Designed deep learning pipelines to predict childhood leukemia and eye disease risks with DNA methylation
  • Built bioinformatics pipelines for germline/somatic variant discovery with WGS data
  • Trained new PhD students and pediatrician research fellows
 
 
 
 
 

Research Affiliate

University of California, Berkeley, School of Public Health

Jul 2019 – Nov 2022 Berkeley, CA

  • Carried out childhood leukemia GWAS analyses; pesticide exposure EWAS analyses
  • Assessed telomere length and aging changes in children with childhood leukemia
  • Managed and monitored proper use of UC Berkeley HPC and delivered routine reports on research progress
 
 
 
 
 

Predoctoral research fellow, Research Assistant

University of Southern California, Center for Genetic Epidemiology

Jun 2019 – May 2022 Los Angeles, CA

  • Conducted high-throughput association models to investigate associations between disease risks and neonatal genetics, epigenetics, cytokines, T-cell receptors, and nucleated cell proportions
  • Performed ancestry analysis to investigate contribution of European ancestry to Latino population disease risks
 
 
 
 
 

Clinical Researcher (Volunteer)

Zhongshan Hospital

Sep 2014 – Jun 2018 Shanghai, China

  • Applied machine learning methods to predict portal pressure and patient outcome from CT-based radiomics
  • Collaborated with surgeons and internal doctors on data collection, experiment design and manuscript writing

Skills

R

Python

Linux/Unix (HPC)

SAS

JAVA

STATA

SPSS

SQLITE

C

Data Analysis

Data Cleaning, Visualization

Modelling

Prediction, Machine Learning, Deep Learning

Clinical analysis

Ancestry Analyses, Survival Analyses

Bioinformatics

EWAS, GWAS (SNPTEST, PLINK), GATK, Singularity

Languages

English, Mandarin, Japanese

Certificates

High-Dimensional Data Analysis (PH525.4x)

See certificate

Statistical Inference and Modeling for High-throughput Experiments (PH525.3x)

See certificate

Introduction to Linear Models and Matrix Algebra (PH525.2x)

See certificate

Statistics and R (PH525.1x)

See certificate

Publications

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Background While recent sequencing studies have revealed that 10% of childhood gliomas are caused by rare germline mutations, the role of common variants is undetermined and no genome-wide significant risk loci for pediatric CNS tumors have been identified to date. Methods Meta-analysis of three population-based genome-wide association studies (GWASs) comprising 4,069 children with glioma and 8,778 controls of multiple genetic ancestries. Replication was performed in a separate case-control cohort. Quantitative trait loci analyses and a transcriptome-wide association study were conducted to assess possible links with brain tissue expression across 18,628 genes.

Abstract Background Genetic variants can modulate phenotypic outcomes via epigenetic intermediates, for example at methylation quantitative trait loci (mQTL). We present the first large-scale assessment of mQTL at human genomic regions selected for interindividual variation in CpG methylation, which we call correlated regions of systemic interindividual variation (CoRSIVs). These can be assayed in blood DNA and do not reflect interindividual variation in cellular composition. Results We use target-capture bisulfite sequencing to assess DNA methylation at 4086 CoRSIVs in multiple tissues from each of 188 donors in the NIH Gene-Tissue Expression (GTEx) program.

Background Epigenome-wide association studies (EWAS) have helped to define the associations between DNA methylation and many clinicopathologic and developmental traits. Since DNA methylation is affected by genetic variation at certain loci, EWAS associations may be potentially influenced by genetic effects. However, a formal assessment of the value of incorporating genetic variation in EWAS evaluations is lacking especially for multiethnic populations. Methods Using single nucleotide polymorphism (SNP) from Illumina Omni Express or Affymetrix PMDA arrays and DNA methylation data from the Illumina 450 K or EPIC array from 1638 newborns of diverse genetic ancestries, we generated DNA methylation quantitative trait loci (mQTL) databases for both array types.

Background: In Down syndrome (DS) there is a high occurrence of congenital hypothyroidism (CH) and subclinical hypothyroidism (SH) early in life. The etiology of CH and early SH in DS remains unclear. Previous research has shown genome-wide transcriptional and epigenetic alterations in DS. Thus, we hypothesized that CH and early SH could be caused by epigenetically driven transcriptional downregulation of thyroid-related genes, through promoter region hypermethylation. Methods: We extracted whole blood DNA methylation (DNAm) profiles of DS and non-DS individuals from four independent Illumina array-based datasets (252 DS individuals and 519 non-DS individuals).

Aberrant DNA methylation constitutes a key feature of pediatric acute lymphoblastic leukemia at diagnosis, however its role as a predisposing or early contributor to leukemia development remains unknown. Here, we evaluate DNA methylation at birth in 41 leukemia-discordant monozygotic twin pairs using the Illumina EPIC array on archived neonatal blood spots to identify epigenetic variation associated with development of pediatric acute lymphoblastic leukemia, independent of genetic influence. Through conditional logistic regression we identify 240 significant probes and 10 regions associated with the discordant onset of leukemia.

Background Periconceptional folate intake is associated with the establishment of DNA methylation in offspring; however, variations in this relationship by food sources versus folic acid supplements are not described. Also, maternal folate intake is associated with decreased risk of pediatric acute lymphoblastic leukemia (ALL), but the mechanism is not known. Objectives We evaluated the relationship between periconceptional folate intake by source and DNA methylation at birth in a cohort of pediatric ALL cases and controls in an epigenome-wide association study.

Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. PA has at least a 50% higher incidence in populations of European ancestry compared to other ancestral groups, which may be due in part to genetic differences. We first compared the global proportions of European, African, and Amerindian ancestries in 301 PA cases and 1185 controls of self-identified Latino ethnicity from the California Biobank. We then conducted admixture mapping analysis to assess PA risk with local ancestry.

Acute lymphoblastic leukemia (ALL) in children is associated with a distinct neonatal cytokine profile. The basis of this neonatal immune phenotype is unknown but potentially related to maternal-fetal immune receptor interactions. We conducted a case-control study of 226 case child-mother pairs and 404 control child-mother pairs to evaluate the role of interaction between HLA genotypes in the offspring and maternal killer immunoglobulin-like receptor (KIR) genotypes in the etiology of childhood ALL, while considering potential mediation by neonatal cytokines and the immune-modulating enzyme arginase-II (ARG-II).

Genome-wide association studies have identified a growing number of single nucleotide polymorphisms (SNPs) associated with childhood acute lymphoblastic leukemia (ALL), yet the functional roles of most SNPs are unclear. Multiple lines of evidence suggest epigenetic mechanisms may mediate the impact of heritable genetic variation on phenotypes. Here, we investigated whether DNA methylation mediates the effect of genetic risk loci for childhood ALL. We performed an epigenome-wide association study (EWAS) including 808 childhood ALL cases and 919 controls from California-based studies using neonatal blood DNA.

Abstract Accelerated aging is a hallmark of Down syndrome (DS), with adults experiencing early-onset Alzheimer’s disease and premature aging of the skin, hair, and immune and endocrine systems. Accelerated epigenetic aging has been found in the blood and brain tissue of adults with DS but when premature aging in DS begins remains unknown. We investigated whether accelerated aging in DS is already detectable in blood at birth. We assessed the association between age acceleration and DS using five epigenetic clocks in 346 newborns with DS and 567 newborns without DS using Illumina MethylationEPIC DNA methylation array data.

Down syndrome (DS) is caused by constitutional trisomy of chromosome 21 and is associated with an up to 30-fold increased risk of acute lymphoblastic leukemia (ALL). While DS is associated with alterations in epigenetic markers, including DNA methylation, and gene expression. These mechanisms have not been fully explored in relation to DS-ALL etiology. Because the epigenome is sensitive to genetic and environmental influences during fetal development and can be leveraged to characterize blood cell proportions, we sought to evaluate the role of the neonatal methylome in children with DS on subsequent ALL risk.

Background: Childhood glioblastoma multiforme (GBM) is a highly aggressive disease with low survival, and its etiology, especially concerning germline genetic risk, is poorly understood. Mitochondria play a key role in putative tumorigenic processes relating to cellular oxidative metabolism, and mitochondrial DNA variants were not previously assessed for association with pediatric brain tumor risk. Methods: We conducted an analysis of 675 mitochondrial DNA variants in 90 childhood GBM cases and 2,789 controls to identify enrichment of mitochondrial variant associated with GBM risk.

Abstract: Infections and antigenic exposures during childhood are associated with pediatric acute lymphoblastic leukemia (ALL) and are thought to lead to immune dysregulation stimulating pre-leukemic clones to expand and progress to overt leukemia. Emerging epidemiologic and laboratory evidence suggests cytomegalovirus (CMV) may contribute to the development of childhood ALL inspiring further investigative efforts and for the first time, identifying a specific target for ALL prevention. In this study, we aimed to better elucidate the role of CMV in ALL etiology by screening diagnostic leukemia bone marrow samples for CMV DNA using a highly quantitative droplet digital PCR (ddPCR) assay.

We performed a trans-ethnic GWAS of childhood ALL in a discovery panel of 76,317 individuals, including 3482 cases and 72,835 controls distributed across four ethnic cohorts (African Americans, AFR; East Asian Americans, EAS; Latino Americans, LAT; Non-Latino White Americans, NLW; Supplemen- tary Information). After quality control filtering, our dataset consisted of 124, 318, 1878, 1162 cases and 2067, 5017, 8410, 57,341 controls in AFR, EAS, LAT, and NLW, respectively. Furthermore, we tested the association at 7,628,894 imputed SNPs, including low frequency (minor allele frequency, MAF, between 1–5%) variants that were not previously systematically tested.

Background: Parental smoking is implicated in the etiology of acute lymphoblastic leukemia (ALL), the most common childhood cancer. We recently reported an association between an epigenetic biomarker of early-life tobacco smoke exposure at the AHRR gene and increased frequency of somatic gene deletions among ALL cases. Methods: Here, we further assess this association using two epigenetic biomarkers for maternal smoking during pregnancy-DNA methylation at AHRR CpG cg05575921 and a recently established polyepigenetic smoking score-in an expanded set of 482 B-cell ALL (B-ALL) cases in the California Childhood Leukemia Study with available Illumina 450K or MethylationEPIC array data.

Summary: Medulloblastoma (MB) is a malignant pediatric brain tumor arising in the cerebellum. Although abnormal GABAergic receptor activation has been described in MB, studies have not yet elucidated the contribution of receptor-independent GABA metabolism to MB pathogenesis. We find primary MB tumors globally display decreased expression of GABA transaminase (ABAT), the protein responsible for GABA metabolism, compared with normal cerebellum. However, less aggressive WNT and SHH subtypes express higher ABAT levels compared with metastatic G3 and G4 tumors.

Abstract Down syndrome is associated with genome-wide perturbation of gene expression, which may be mediated by epigenetic changes. We perform an epigenome-wide association study on neonatal bloodspots comparing 196 newborns with Down syndrome and 439 newborns without Down syndrome, adjusting for cell-type heterogeneity, which identifies 652 epigenome-wide significant CpGs (P < 7.67 × 10−8) and 1,052 differentially methylated regions. Differential methylation at promoter/enhancer regions correlates with gene expression changes in Down syndrome versus non-Down syndrome fetal liver hematopoietic stem/progenitor cells (P < 0.

Abstract Context: Radical cystectomy (RC) has complicated surgical procedures and various ways of urinary reconstruction. Aims: The aim of this study is to investigate whether the advantages of laparoscopy over open surgery were consistent in the perioperative recovery of different methods of urinary diversion after RC in the general and the elderly (>65 years) population. Settings and design: A retrospective study reviewed 452 (elderly 261) patients who received RC from the year 2005-2012.

Abstract Introduction: Prostatic stromal tumor of uncertain malignant potential (STUMP) is a rare disease that may coexist with prostate stromal sarcoma (PSS). We aimed to analyze the histological and clinical features of STUMP. Methods: Twenty-three patients diagnosed with STUMP from 2008 to 2019 were included. Clinicopathological and follow-up information was collected. In the subgroup analysis, we divided the patients into a pure STUMP group (N = 18) and a mixed STUMP (STUMP coexisting with PSS) group (N = 5).

Abstract Background: The distribution characteristics of inflammatory cells in hyperplastic prostatic tissue and its influences on disease development remain unknown. We aimed to explore the infiltration characteristics of different inflammatory cells in histological structures of benign prostatic hyperplasia (BPH) in combination with clinical data. Methods: The present study included 76 cases of BPH patients underwent transurethral resection of prostate (TURP). Hematoxylin-eosin staining was performed to identify the degree of general inflammation in prostatic tissues.

Abstract Background: Non-schistosoma-associated urinary bladder squamous cell carcinoma (SqCC) has low incidence and is associated with chronic inflammation. Due to its unique etiology and pathology, expression of programmed cell death ligand 1 (PD-L1) in SqCC could be different from that of urothelial carcinoma, which may contribute to different responses to immunotherapy. In this study, we intended to explore the expression profile and prognostic value of PD-L1 in non-schistosoma-associated urinary bladder SqCC under the consideration of tumor-infiltrating lymphocytes’ (TILs) density.

Abstract Purpose Portal venous pressure (PVP) measurement is of clinical significance, especially in patients with portal hypertension. However, the invasive nature and associated complications limits its application. The aim of the study is to propose a noninvasive predictive model of PVP values based on CT-extracted radiomic features. Methods Radiomics PVP (rPVP) models based on liver, spleen and combined features were established on an experimental cohort of 169 subjects. Radiomics features were extracted from each ROI and reduced via the LASSO regression to achieve an optimal predictive formula.

Abstract Background: Metabolic syndrome (MetS) has been found to be prevalent in cancer and have implications in cancer outcomes. In this study, we attempted to evaluate the prognostic value of MetS in localized clear cell renal cell carcinoma (ccRCC) patients. Methods: We retrospectively collected clinicopathological data and pre-treatment laboratory test results of 480 patients with localized (T1-2N0M0) ccRCC undergoing radical or partial nephrectomy in Peking University First Hospital. MetS was diagnosed by criteria of the 2004 Chinese Medical Association Diabetes Society.

Abstract Objectives: Albumin-globulin ratio (AGR) has been reported as an independent risk factor for survival outcomes of a variety of malignancies. We aimed to further examine the prognostic value of AGR for urothelial carcinoma of bladder (UCB) using a propensity score-matched (PSM) analysis. Materials and methods: The medical data of 189 high-grade UCB patients undergoing radical cystectomy were retrospectively reviewed. AGR was defined as the ratio of serum albumin to nonalbumins (serum total protein-albumin).

Abstract Aims Cytoplasmic polyadenylation element binding proteins (CPEBs) are RNA-binding proteins that regulate translation by inducing cytoplasmic polyadenylation. CPEB4 has been reported in association with tumor growth, vascularization, and invasion in several cancers. To date, the expression of CPEB4 with clinical prognosis of breast cancer was never reported before. We aim to investigate the expression of CPEB4 and its prognostic significance in invasive ductal breast carcinoma. Methods Immunohistochemical staining of CPEB4 and estrogen receptor, progesterone receptor, and human epidermal growth factor receptor was performed in 107 invasive ductal carcinoma (IDC) samples, and prognostic significance was evaluated.

Other Skills

Digital multimedia production.

Proficient in graphic and video productions using Adobe Suite (Photoshop, Illustrator, Lightroom, After Effect), and Apple Final Cut Pro.

USC KSOM Commencement Video (2021)

Producer USC Keck School of Medicine Virtual Commencement Videos (2021)

USC KSOM Research Video

First Prize in Keck School of Medicine Research Video Competition (2020)

USC KSOM Commencement Video (2020)

Producer USC Keck School of Medicine Virtual Commencement Videos (2020)

BEC Short Video

First Prize of Cambridge Business English China short video competition (2012)

UNMDG Video

First Prize of U21 United Nations Millennium Development Goals (UNMDG) Student Video Competition (2012)

Watch more of my videos

I make vlogs sometimes, if that interests you.

My other miscellaneous projects

My vlogs