Genomics of Gene Regulation (NHGRI, 2015-2018)
Glucocorticoids are among the most widely used drugs to reduce inflammation and immunity. Their long term use is limited by adverse metabolic effects that these drugs have. Within weeks of treatment, patients start to see changes in where their bodies store fat. Some patients even begin to develop diabetes. The goal of this project is to develop a deep enough understanding of how genes are used after glucocorticoid treatment so that we can ultimately start to reprogram the response to our own design. Specifically, we will attempt to design derivative cell types that maintain the inflammatory response but have a reduced metabolic response. The ability to do so would pave the way for new understanding of how these important drugs work, and could inform new therapies that have a more targeted anti-inflammatory effect.
Engineering Targeted Epigenetic Modifiers for Precise Control of Gene Regulation (NIH, 2013 – 2018)
The human genome is a very busy place. Along the tiny strands of billions of A’s, C’s, G’s, and T’s that make up “The Human Genome”, there are thousands of different types of regulatory proteins bound in all sorts of different configurations and complexes. This is part of the reason why we can pack so much DNA into a single cell. While many proteins just bind the genome and go away later, there are specific types of proteins that go further and actually modify the structure of the genome. These modifications (collectively known as the epigenome) are turning out to be very important in understanding how our genes are regulated. The goal of this project is to develop a toolbox that will allow us to take control of the epigenome and begin to understand how it is that these different epigenome modifications determine the genes that are used in different cells and tissues.
Genetics and Genomics of Maternal Glycemia During Pregnancy (NIDDK, 2013 – 2018)
There is something about pregnancy that causes many women to develop a specific form of diabetes known as gestational diabetes. Diabetes occurs when your body is not able to regulate sugar, and it can lead to all sorts of really bad outcomes. Gestational diabetes is particularly troublesome because it causes health problems for both the mother and the unborn child. A recent study suggests that changes in gene regulation in a particular region of the genome may contribute to gestational diabetes by altering the ability of some women to process sugar after a meal. The goal of this project is to identify those regulatory mutations, and to understand how they may contribute to maternal sugar metabolism.
Genetics and Genomics of Fetal Adiposity (NIDDK, 2013 – 2018)
Baby fat may be more than just cute. It turns out that most animals including monkeys all have really skinny babies, and human babies are unique in that they have so much fat at birth. Some researchers now think that this fat store provides energy that is important to brain development just after birth. In other words, human baby fat might be part of the reason why the human brain is capable of so much! A recently study suggests that one of the things that controls how much fat human babies have has to do with genetic changes in gene regulation. The goal of this project is investigate the role of those candidate regulatory mechanisms on expression of genes involved in the development of baby fat.
The ENCODE Project Consortium (NHGRI, 2012 – 2017)
Every cell in our bodies has roughly the same copy of the genome (the A’s, C’s, G’, and T’s that define the human species). Within each genome is the blueprint for (at least) tens of thousands of genes. If you go in and look at individual cells and tissues, however, you will find that the genes that are actually in use varies dramatically between the different tissues. This explains how we get such a huge diversity of cell types from a single blueprint. There is also a lot of recent evidence telling us that when genes are not regulated in the correct way it can lead to disease. The goal of this project is to ultimately develop a comprehensive understanding of how human genes are regulated. Doing so requires a massive and systematic effort that is spread across many different labs, and we are contributing to that effort by developing more precise ways to pinpoint where regulatory proteins bind the genome and to understand what the effect of that binding is on gene expression.