Research Report 2019_20


Brian Roberts and Chris Partridge, PhD

Jacob Loupe, PhD

Lindsay RIzzardi, PhD

Matthew Knuesel, PhD and Sophie Guo

Bri Rodgers and Nick Cochran, PhD

A few of the members of the Myers Lab working on human health research

The goal after identifying transcription factors is to use a variety of approaches to turn down the expression of mutated genes in hopes of mitigating the effects of the disease. Several HudsonAlpha labs, including Myers’ lab, along with several other institutes are sequencing and analyzing thousands of patient samples from with- in the state of Alabama and around the world to learn more about the genetic causes of diseases of the ner- vous system. These studies have helped identify genes involved in ALS 3 , Alzheimer disease 4 , FTD and bipolar disorder 5 . In one such study, Cochran helped collabora- tors in California and Colombia, South America find a never-before-identified mutation on PSEN1 , a gene known to cause Alzheimer Disease 4 . This finding is helping improve efficacy in clinical trials for drugs to treat the disease. By gaining a better understanding of the genetic and genomic bases of neurological disorders, Myers’ lab hopes to identify genes and transcriptional pathways that will lead to predictive biomarkers for the disorders and responses to treatments, as well as new targets for therapies. A project led by postdoctoral fellow Ben Henderson is searching for RNA and DNA markers in plasma from individuals with Alzheimer disease and Huntington disease that are indicative of the presence of the disease, even prior to onset of symptoms. n

In a related study published in Genome Research , Myers’ lab, along with Sara Cooper’s lab at Hudson- Alpha, analyzed ENCODE data to characterize regions of DNA with high numbers of transcription factor binding events, called high occupancy target (HOT) loci 2 . Clas- sically, gene regulatory loci are thought to be bound by only a small subset of transcription factors. However, by using two methods to find DNA binding associations across the genome, the group found about 15,000 HOT loci that could be bound by more than twenty five per- cent of the DNA binding proteins assayed. The study also presents evidence that regulatory activity is localized to a few hundred base pairs within each HOT locus. Myers’ lab also studies particular transcription factors and networks of factors involved in human brain biology and disorders of the nervous system, such as Huntington disease, Alzheimer disease, fron- tal temporal dementia (FTD), ALS, bipolar disor- der, schizophrenia, and ALS. Members of Myers’ lab, including senior scientists Brian Roberts, Nick Cochran, PhD, Jacob Loupe, PhD, Lindsay Rizzardi, PhD, Matthew Knuesel, PhD, and graduate stu- dent Bri Rogers, are using a variety of experimental approaches and cultured human neuronal cells to iden- tify transcription factors and their binding sites in and near genes responsible for neurodegenerative diseases, particularly Huntington disease and Alzheimer disease.

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