Research Interests:

We are developing experimental and computational tools that will allow biologists to collect high volumes of quantitative data on nucleic acids and proteins. We are also focused on using these tools to understand, at a molecular level, how complicated cellular processes like transcription and alternative splicing are regulated and coordinated.
Some specific areas that we are focused on are listed below:

1. Single Molecule Detection of Proteins.  Finding biomarkers that can predict disease state would greatly improve patient care because many diseases can be effectively treated if they are caught early enough.  However, it is still difficult to find good disease biomarkers because existing technologies are not sensitive or quantitative enough to accurately measure a large number of low-abundance biomolecules, such as proteins.  We are developing a technology that we hope will cost-effectively and accurately measure genome-wide protein abundance and, at the same time, allow for the analysis of post-translational modifications.

2. New Molecular Tools That Utilize Next-Generation Sequencing Technology.  The cost of DNA sequencing has dropped almost 100-fold over the past two years, and this trend will continue.  We are developing molecular tools that leverage this drop in next-generation sequencing cost to answer new biological questions.  We are developing new methods to detect rare somatic and germline mutations, to measure global mRNA expression levels from a large number of single cells, and to analyze methylation patterns in different tissues.

3. How Are Gene Networks Regulated?  Eukaryotic cells perform a number of important functions -- they move, grow, divide, differentiate, communicate, and respond to their environments.  The cell’s ability to execute such varied tasks is largely due to the complex and precise orchestration of gene transcription. The information that ensures a gene is expressed at the right time and at the right level is often encoded in nearby regulatory sequences, but we still do not know how this information is encoded.  A number of basic questions still remain unanswered: Why do so many transcription factor binding sites appear inactive? How do TF binding sites interact to modulate transcriptional patterns? How much of a gene’s expression is determined by nearby regulatory elements and how much is determined by the local state of the chromatin? How does genetic variation influence expression patterns of genes and through what mechanisms does it do so? We are performing experiments using the model organism S. cerevisiae that will help answer some of these questions.