Trypanosoma cruzi is a neglected tropical disease that is rarely diagnosed in its acute phase, leading to severe health outcomes later in life. The parasite is currently endemic to Central and South America but is spreading north as climate change increases the range of its triatomine insect vectors. It is estimated that 6 million people in the Americas are currently infected with T. cruzi, including 600,00 people within the US.The broad aim of this proposal is to understand the molecular mechanisms that T. cruzi employs to infect its host.

Genomic data has become an increasingly widely used source of information in the fight against infectious disease outbreaks. Often called "genomic epidemiology", the mutations observable in a pathogen's genome allow us to reconstruct its distribution, spread and evolution over time. Nowhere has this been more clearly demonstrated than during the COVID-19 pandemic.

Epistasis, commonly defined as the interaction between genetic loci, has long been hypothesized to play a key role in defining the genetic architecture underlying complex traits. However, despite the recent strong evidence of pervasive epistasis in many array- and sequence-based genome-wide association studies, statistical methods for powerfully mapping epistatic effects remain in their infancy. Existing epistatic mapping methods explicitly search over all pairwise or higher-order interactions when identifying significant nonlinear effects among genome-wide variants.

Candida species are a frequent and serious cause of bloodstream infections in the clinic.  Despite access to several antifungal drugs, systemic infections are associated with mortality rates that can exceed 40%.  In many patients, the organism persists in the bloodstream during antifungal treatment, despite the fact that recovered isolates are not drug resistant when tested in vitro.  The mechanisms responsible for such clinical persistence are unknown, but persistence is critically associated with therapeutic failure, recurrent infection and reduced survival.  Our preliminary studies indic

Current antibiotic therapy can lead to microbiome related complications and shifts in microbial populations that can contribute to the spread of antibiotic resistance. The work proposed here will transcriptionally profile the impacts of antibiotics on the composition and function of the oral microbiome in clinical samples. This functional information can identify therapies that more effectively utilize our current arsenal of antimicrobials in order to combat the impending antibiotic resistance crisis.

Aging is a major risk factor for a number of diseases, including neurodegenerative diseases, diabetes, and cancer. However, the mechanisms responsible for aging remain poorly understood. Work from our lab and others has linked a particular family of proteins, known as FOXOs, to healthy aging in various species, including humans. The goal of this project is to understand how the different FOXO family members contribute to cellular maintenance in humans.

Cholangiocarcinoma (CCA) is a devastating disease with a 5-year survival rate of 2%. The incidence of CCA has increased almost two-fold over the last three decades in the United States, and as such, there is an urgent need to find effective therapies for this lethal disease. Understanding the molecular pathogenesis of CCA development may lead to strategies for intervention and treatment. Recently, IDH1 and IDH2 mutations have been identified in about 20% of CCA patients.

Gene regulatory mechanisms are critical for proper cellular and protein function, and modern molecular biology techniques have linked numerous pathologies to dysregulation of genes. However, faithful modification of the genome in studies of pathogenic mutations and associated mechanisms have been difficult, rarely leading to effective treatments. The advent of CRISPR-Cas9 (Cas9) as an inexpensive tool for genome editing has created new possibilities for therapeutic gene targeting.

In this study, we propose to use a graph-based deep learning framework to integrate information about the 3D organization of the DNA and its environment to predict gene expression. Gene regulation is the process of controlling the expression of genes to go high or low. Any disruption in this process can have severe downstream consequences and result in diseases like cancer. Promoters and regulatory elements, like enhancers and repressors, spatiotemporally participate in gene regulation.

Sexually transmitted infections (STIs) remain a hidden epidemic of significant health and economic consequence in the United States and the world. Available therapies against many STIs, including HIV and HSV, do not provide a long-term cure, have significant side effects and can be cost-prohibitive.