Adipose tissue secretes cytokines to regulate essential functions, but comprehensive study is prevented by difficult-to-access depots such as visceral epicardial adipose tissue and differences between donor sources and methods to generate cell lines. This project will start with an isogenic population of cultured human preadipocytes and reprogram them to specific types of adipocytes using a combinatorial process analogous to that of induced pluripotent stem cells. This project includes working with single cell (sc)-RNAseq and sc-ATACseq datasets using XGBoost and other models.

Our research focuses on understanding how genetic polymorphisms influence disease by affecting transcriptomic and epigenomic profiles in the immune system. However, most of these genetic polymorphisms are located within the non-coding regions of the genome, which are areas that do not directly code for proteins. This makes their interpretation particularly challenging, as their functional role is not immediately apparent. We use next-generation sequencing technologies to identify genetic polymorphisms associated with molecular traits, like changes in gene expression, and leverage information from epigenomic data (ChIP-seq, ATAC-seq, etc.) to pinpoint disease mechanisms.

Identifying genetic variants associated with transcription factor binding. We have implemented a published linear regression model to analyze the allele frequency within DNA, enriched using chromatin immuno-precipitation techniques for variant discovery in primary human immune cell subsets. The relevance of this research is to narrow down the molecular mechanism by which non-coding genetic variants may influence gene expression, contribute to complex phenotypes and influence an individual's susceptibility to disease.

We have assembled a large cohort of donors with various head&neck cancers, who have kindly provided matched tumorigenic and healthy adjacent tissue samples. We have profiled a set of immune cells from these samples, namely T cells, which have been extensively shown to play an important role in cancer immunotherapy. Analyses of the healthy adjacent tissue samples are undergoing, and we will be reporting on a comprehensive T-cell atlas of the head&neck compartments. Yet, there remain massive data from the tumor-related side of the project to be analyzed. These data include single-cell RNA-seq, surface protein expression and T-cell receptor (TCR)-seq modalities, all spanning multiple anatomical sites as well as different types of head&neck cancers.

The Amariuta Lab sometimes has bandwidth to take on talented undergraduate students with research or course experience in bioinformatics and statistical data analysis. We have a variety of predefined projects but are also open to student-led projects and ideas that fall within the general scope of research in our lab. These projects generally involve mapping the genetic component of gene expression and, separately, complex traits and polygenic diseases, in order to identify putative disease-critical genes that could serve as predictive biomarkers or therapeutic targets. All projects are in the area of statistical and population genetics, aiming to understand population-specific and shared genetic effects across diverse cell types and tissues, via the integration of high dimensional genomic data with globally diverse DNA sequence (genotyping) and disease data (phenotyping).

The Amariuta Lab is happily accepting PhD rotation students. We have a variety of predefined projects but are also open to student-led projects and ideas that fall within the general scope of research in our lab. One potential rotation project involves the investigation of different ways to estimate gene expression heritability (e.g., the proportion of gene expression variance that can be explained by genetics), including using cutting edge fine-mapping algorithms and single cell RNA-sequencing data. A second potential project involves developing a new method to map the cell-type-specificity of the genetic component of gene expression regulation, which is often confounded by strong patterns of co-expression and co-regulation across genes and other cell types. A third potential project involves mapping the causal genes underlying putative causal tissues and cell types mapped via our previously published method called Tissue Co-regulation SCore regression (TCSC). A fourth potential project involves identifying putative causal tissues and cell types underlying the genetic correlation and hence pleiotropy of immune-mediated diseases. Lastly, we are also beginning to explore deep learning models to use sequence data to predict gene expression levels in novel ways and would welcome students who wish to gain skills in any of these areas.

The implementation of functional precision medicine, which combines genomic profiling with drug sensitivity testing of patient’s tumor cells, has potential to identify personalized and effective treatment options. This project aims to build treatment-response models based on available molecular profiles and patient-matched drug-response data obtained from pediatric brain tumor patients at Rady Children’s Hospital San Diego and at other cancer centers. The goal is to predict novel drug and biomarker pairs to enable better treatment decisions.