PhD Projects


Primary Project


Characterizing small non-coding RNAs in the human placenta

The human placenta is the indispensible organ necessary for all water, nutrient, gas, and waste exchange between the mother and fetus; as such gene expression is tightly regulated. Gene regulation is carried out a number of mechanisms, and gene repression by small non-coding RNAs (sncRNAs) is one of these processes. Exclusive placentally-expressed sncRNA loci in the placenta have been identified, however, studies have routinely focused on only one species of sncRNA (microRNAs).

My project aims at:

  1. Characterizing the sncRNA species that are present in the human placenta and 4 placental cell types (trophoblasts, endothelial cells, stromal cells, HofBauer cells)
  2. Investigating novel sncRNA species
  3. Cataloguing the ones that differ in expression by different variables (like trimester of the pregnancy, sex of the fetus, ancestry, depression and anti-depressant status of the mother, and a few others).

DNA methylation is another epigenetic regulatory mechanism, and the placenta has been recognized for its unique epigenetic landscape. The sncRNA expression data observed will be integrated with sample-matched DNAm data to investigate whether any correlation in expression exists between the two gene regulation mechansisms. The placental gene expression profile also resembles that of cancer, and the top sncRNAs of interest will be examined for their connection to cancer progression.

Software: R Programming. Some of my code is available on my GitHub.

Project Impact:

  • Self-taught R, RMarkdown, and RNA-seq data analysis
    • quality control, normalization, PCA, linear modeling, DNAm correlation, gene/pathway enrichment
  • First instance of large-scale trancriptomic sequencing of the human placenta.
  • Establishment of the normative placental transcriptomic profile by several inherent biological variables, and extrinsic technical and environmental variables.
  • Correlation to some cardiovasuclar and cancer pathway genes
  • Pilot analysis showed that there indeed are microRNAs differentially-expressed by trimester


Communication:

Project Overview
European Society of Human Genetics (ESHG) 2023 Conference Talk
BCCHR: Healthy Starts Research Day 2021 - Poster
UBC Department of Medical Genetics Research Day (2020,2021)
EMBO–EMBL Symposium: The Non-Coding Genome
International Federation of Placental Research (IFPA) 2021
University of Toronto Health Network (UHN) Seminar Series - Invited

Collaborations


1. BC Children’s Hospital Research Institute / The Ted Steiner Lab

An IBD-mimic human colonoid chronic-injury model

Intestinal cells undergo regeneration after acute injury. However, the feasibility and capacity of these cells to undergo repeated renewal and regeneration on chronic injury is still not well understood. Using intestinal epithelial cells collected from 2 human patients, colonoid organoids were generated in the lab and were further subjected to rounds of induced damage, inflammation and rescue to observe the renewal mechanisms of these cells

I was recruited as a Bioinformatician for this exploratory project to analyze their RNA-seq data, for which I was given second-authorship on the respective manuscript

Data/Software: mRNA-seq / R, GSEA

Project Impact:

2. BC Children’s Hospital Research Institute / The Gregor Reid Lab

Investigating the dynamic immunophenotypic cell population changes during childhood acute lymphoblastic leukemia (ALL) relapse

I trained the first-author physician-scientist in R Programming, which was used to generate all the comparitive plots in the article


Data/Software: human mRNA-seq / R

Project Impact: Manuscript submitted to Nature Cancer

3. Centre for Heart Lung Innovation: St. Paul’s Hospital / The Decheng Yang Lab

Role of NF activated T-cells in the Pathogenesis of Coxsackievirus-induced Myocarditis


In progress: Manuscript writing

Data/Software: murine mRNA-seq / R, GSEA

4. BC Cancer Research Centre / The Kevin Bennewith Lab

Telmisartan treated tumours show an improved response to radiaition therapy


In progress: Follow-up validation experiments of in-silico results

Data/Software: human + murine single-cell RNA-seq / R

5. Djavad Mowafaghian Centre for Brain Health / The Yu Tian Wang Lab

Notch1 signaling plays an essential role in metabolic rewiring in docetaxel resistance prostate cancer


In progress: Manuscript writing

Data/Software: human mRNA-seq / R

Master’s Project


Comparing the Genetic Architecture of Lipid Traits between Populations

The majority of Genome-wide Association Studies, even now, focus on Caucasian, European populations. Genetic differences exist people of differing populations, where people of a certain ancestry or ethnicity can have genetic variants not present in those of European popualtions. These variants can lead to variable gene expression, as well as a differential response to drugs admistered. Hence, the resulsts of these single-poulation centric studies cannot be extrapolated to different populations. There is, therefore, an increased need to conduct such genome-wide studies in several other populations, along with accounting for population differences in large-scale studies.

I collected GWAS summary statistics of three lipid (cholesterol) biomarkers from seven different populations (British, two Greek isolates, Chinese, Japanese, East Asian, Ugandan) calculated the Polygeneic Risk Scores (PRSs) of each individual using the commonly overlapping lipid SNPs to assess if these scores varied across the populations. The heritability as well as trans-ancestral correlation was also calculated. The measured blood lipid biomarker levels were then examined across the genetic scores, to investigate the correlation between the blood lipid levels of one biomarker against the genetic score of another (biomarker-score cross association).

Software: UNIX, command-line R, PLINK, GEMMA, Popcorn

Results:

  • The majority of European CVD/lipid loci overlap with the Japanese, Chinese, Greek-isolate, and African Ugandan populations.
  • HDL biomarker/score showed an inverse relationship with LDL biomarker score; LDL and Triglycerides had a linear relationship, except for in the Ugandan population where triglyceride score did not correlate with biomarker score.
  • The two Greek-isolate populations showed near perfect heritability and trans-ethnic correlation with the UK population, same as the Japanese and Chinese population with the East Asian population.

Project Impact:

  • Opportunity to work as as a Visiting Scientist at the Wellcome Sanger Institute
  • Second-author publication in Nature Communications
  • PRSs available on EMBL-EBI’s PGS Catalog
  • First comparison study of its kind: Lipid phenotype (lipid blood levels) was found to be associated with lipid genotype (PRS)

Undergraduate Summer Research


Using WNT5A Expression to Characterize Development in the Human Gut

The WNT genes are known to participate in genetic pathways involved in cell patterning, signalling, and proliferation during development. WNT5A in particular is invloved in a number of syndromes which are caused by abnormal cell signalling or growth. The gut (made up of the esophagus, intestines, and anus) is one of the organs that grows and elongates the most during embryonic develpement.

Using immunohistochemistry, I measured the presence of the WNT5A protein the human embryonic gut at Carnegie Stage 20 (~50 days post conception).


Project Impact: