Projects

Current Projects

Chronic Traumatic Encepthalopathy and the Pan-Neurodegenerative Disease Phenotype

Current as of 2/22/2019

PI: Adam Labadorf
Hub Analyst: Ikjot Sidhu

Chronic Traumatic Encephalopathy (CTE) is increasingly recognized as a ND associated with repetitive acute traumatic brain injury, and brains obtained from individuals with CTE have a higher prevalence of other NDs, including parkinsonism (Lewy bodies) and Alzheimer's Disease. We hypothesize that there is a common set of neuroinflammatory pathways invoked by neurodegeneration across HD, PD, and CTE that is detectable by genome-wide transcriptional analysis measured by high throughput mRNA sequencing (mRNA-Seq).

Genetic Risk Factors in Chronic Traumatic Encephalopathy

Current as of 1/29/2019

PI: Thor Stein
Hub Analyst: Nate Bourgeois

Repetitive head impacts (RHI) are a form of mild traumatic brain injury that can lead to severe cognitive and behavioral symptoms and the progressive neurodegeneration of chronic traumatic encephalopathy (CTE). Trauma is also a known risk factor for Alzheimer disease (AD), and we hypothesize that a prolonged period of RHI can play a causative role in the development of AD as well as CTE. We hypothesize that the AD genetic risk variants APOE and TMEM106B are enriched in CTE and CTE-AD subjects and are associated with altered cytokines and increased levels of beta-amyloid and tau and progression of disease.

small RNA-based biomarkers in Parkinson's Disease CSF

Current as of 3/22/2019

PI: Stephanie Bissonette (MD)
Hub Analyst: Filisia Agus

Small RNAs extracted from Cerebrospinal Fluid (CSF) from PD patients at the BU Movement Disorders Clinic are being evaluated for biomarker potential using small RNA sequencing.

Brain-CSF concordance of microRNA sequencing data in Parkinson's Disease

Current as of 9/4/2018

PI: Rick Myers
Hub Analyst: Ryan Ingram

The goal of this study is to determine if the signature discovered in brains can be detected in the CSF from the same individuals. A state of the art miRNA-Seq analysis pipeline is used to process the datasets and advanced statistical techniques using Firth's logistic regression, cross validation, and bootstrapping are employed to identify miRNAs that are consistently perturbed in PD compared with control tissues.

mRNA-Seq analysis of GPS2 KO vs WT murine adipocytes

Current as of 1/11/2019

PI: Valentina Perissi
Hub Analyst: Joey Orofino (grad student in the Perissi lab)

GPS2 is a small multifunctional protein with known functions in mediating inflammation and lipid metabolism. GPS2 adipose specific knockout mice (GPS2-AKO) display improved systemic insulin sensitivity and lipid storage capacity despite becoming obese. This project aims to characterize the mRNA expression of mature adipocytes from GPS2-AKO mice and explore how changes in gene expression may contribute to this phenotype. High throughput mRNA-Seq datasets were generated using adipocytes isolated from four GPS-AKO and four WT mice and analyzed using a state of the art mRNA-seq pipeline to identify a gene expression signature associated with GPS2 KO.

ALT+ vs ALT- Osteosarcoma Cell Line and Patient Derived Xenograph Gene Expression Signature by mRNA-Seq

Current as of 9/12/2018

PI: Rachel Flynn
Hub Analyst: Anqi (Angel) Dai

This study seeks to identify a gene expression signature using the ALT+ and ALT- cell lines using high throughput mRNA sequencing. We will then use this signature to determine ALT status in primary osteosarcoma tumor samples. A secondary objective will be to use the differentially expressed genes identified by sequencing analysis to determine putative molecular mechanisms underlying the ALT+ phenotype.

Past Projects

mRNA-Seq analysis of affected brain regions in manifest and asymptomatic Huntington’s Disease

Current as of 1/4/2019

PI: Rick Myers
Hub Analysts: Felisia Agus and Diego Crespo

Preprint in bioRxiv

This study characterized and compared the gene expression profile of the caudate nucleus, the brain region most affected in Huntington's Disease, in individuals with confirmed Huntington's Disease mutations but who had not yet developed symptoms by time of death.

Topologically Associated Domain (TAD) Analysis in Post-Mortem Huntington's Disease mRNA-Seq

Current as of 6/12/2017

Internal Hub Project
Hub Analyst: Eve Byington

Measuring the epitranscriptome via engineered RNA POL I and RNASeq in humans and zebrafish

PI: Daniel Cifuentes
Completed 2/2017

Epi-transcriptome m6A Detection by 2OMe-Seq in Zebrafish Development

PI: Daniel Cifuentes
Hub Analyst: Kylie Shen
Completed 8/2017

Microbial RNA-Seq analysis of variable complement-binding streptococcus pneumoniae

Current as of 1/31/2017

Streptococcus pneumoniae is a Gram-positive bacterium that is a common cause of pneumonia, particularly in children and the elderly. The genomes of dozens of SP strains from around the world have been isolated and sequenced, revealing substantial genetic diversity outside of a common set of genes that comprises about 70% of the genome. Recently, two clinically isolated strains of SP have shown variable binding and activation of the C3 complement complex in the immune systems of chinchillas, where some strains induce a stronger immune response associated with better prognosis than others. Neither the genotype nor conventional capsule markers distinguish between these strains, suggesting a transcriptional role might be useful in predicting complement binding status. The Schnyder lab has generated whole-transcriptome deep RNA-Seq datasets for six clinical isolates, three with high-C3 and three with low-C3 binding activity, to identify potential RNA elements associated with binding status. The genomes of these isolates have also been fully sequenced. Cutting edge, custom bioinformatics algorithms are applied to identify differential expression on a synteny- and gene-centric basis.