Lab Projects

Genetic association studies
Regulation of neurodegenerative associated genes
Discovering the function of non-coding genomic regions

Genetic association studies

The Cochran lab studies large data sets of patients with and without neurodegenerative diseases to identify new genes and/or genetic variants that are associated with disease onset and progression. These studies, called genetic association studies, analyze the genomes of many people to find genetic variants associated with a certain disease. Association studies are an important tool for identifying genes conferring susceptibility to complex diseases and disorders. Once new genetic associations are identified, researchers can use the information to develop better tools for detecting, treating, and preventing the disease.

Computational biologist Jared Taylor analyzing a data set

Cochran’s lab, along with many collaborators including others from HudsonAlpha, is measuring genetic data and analyzing thousands of patient samples from within the state of Alabama and around the world to learn more about the genetic causes of neurodegenerative diseases like Alzheimer’s disease. In one such study, Cochran helped collaborators in California and Colombia, South America find a never-before-identified mutation on PSEN1, a gene known to cause AD.  This finding is helping improve efficacy in clinical trials for drugs to treat the disease.

They also participate in several collaborative projects that are addressing the important problem of right-sizing genetic association studies for underrepresented populations. These include the new UAB exploratory Alzheimer’s disease research center with Dr. Erik Roberson with a focus on African American ancestry populations, collaboration with Dr. Kenneth Kosik (UCSB) and Dr. Francisco Lopera (University of Antioquia) for the Colombian population, and collaboration with Dr. Kenneth Kosik (UCSB), Dr. Jennifer Yokoyama (UCSF), Dr. Agustin Ibanez (CONICET, Argentina) and many others as part of the Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat).

ReDLat is a multinational consortium that was launched to expand dementia research in Latin America. The consortium aims to identify the unique genetic and socioeconomic determinants of health that drive Alzheimer’s diseases and other dementias in Latin America. Scientists involved in the project are using neuroimaging, genetic, and behavioral data on over 4,000 individuals from Argentina, Brazil, Chile, Colombia, Mexico, Peru, and the United States to offer a unique understanding of the genetic and environmental underpinnings of dementia.

Regulation of neurodegenerative-associated genes

All the cells in an individual’s body contain the same DNA. However, what differentiates a lung cell from a neuron is the expression of different genes, or whether genes are turned on or turned off. Gene expression is regulated by the binding of transcription factor proteins to short stretches of DNA, called regulatory elements, that serve as “on/off” switches for that gene. The regulation of gene expression controls the timing, location, and amount of gene products in a cell. This allows for the differentiation and development of unique cell types throughout the body but can also lead to disease states if it becomes dysregulated.

Graduate student Bri Rogers looking at fluorescently labeled neurons

Many neurodegenerative diseases are characterized by dysregulation of gene expression where certain genes are expressed more than they need to be or expressed less than they need to be. A prominent theory is that this can lead to a toxic level of accumulation of these proteins in cells (like tau and amyloid-beta in Alzheimer’s disease) that can cause cell damage and cell death. The Cochran lab is focused on investigating gene regulation processes involved in Alzheimer’s disease development and progression. One of the genes that the lab focuses largely on currently is MAPT, the gene that encodes for tau protein which is involved in Alzheimer’s disease pathogenesis.

In addition to finding the DNA regulatory elements, the Cochran lab uses a variety of cutting-edge computational and experimental approaches to study transcription factors and their binding sites in and near genes responsible for Alzheimer’s disease and other dementias. 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. Developing drugs to stop the transcription factors’ ability to turn on genes that drive Alzheimer’s disease pathology could prevent the onset or slow the progression of the disease.

Genome-wide approaches for the function of non-coding genomic regions 

Only about 2 percent of the human genome codes for amino acids, the building blocks of proteins. The remaining 98 percent is made up of non-coding DNA, regions of the genome that do not code for proteins but have other important functions. Many regions of non-coding DNA play a role in the control of gene expression, meaning they help determine when and where certain genes are turned on or off. Other regions of noncoding DNA are important for protein assembly.

Variants in non-coding DNA can turn on a gene and cause a protein to be produced in the wrong place or at the wrong time. Alternatively, a variant can reduce or eliminate the production of an important protein when it is needed. Not all changes in non-coding DNA have an impact on health, but those that alter the pattern of a critical protein can disrupt normal development or cause a health problem.

The Cochran lab studies the effects of rare non-coding variants using functional genomics on established neurodegeneration-associated genes, as well as with unbiased approaches applied across the genome. The lab aims to determine how rare non-coding variants interact with disease-associated cellular processes.