We have moved from UT Southwestern to

Altos Labs, Bay Area Institute of Science, in Redwood City!

What do we do?

Our primary research interest is to understand the emerging roles of the “unannotated genome,” which encodes a whole new class of uncharacterized microproteins. We focus on the relevance and function of this “dark proteome” in regulating development and disease. More broadly, our major goal is to study how gene regulation is controlled at the translational level, and how translational control is misregulated in cancer and other disease contexts. We are exploring these mechanisms using a repertoire of interdisciplinary approaches, including CRISPR-based functional genomics, next generation deep-sequencing techniques, biophysical characterization, and bioinformatics.

Research Areas

the “dark” proteome

More than 15 years after the completion of the Human Genome Project, our understanding of the “annotated” genome is still incomplete. We and others have uncovered a large universe of uncharacterized “microproteins” encoded on unannotated open reading frames (ORFs). However, whether the majority of these microproteins are biologically active, as well as what are their functions, remain to be elucidated. We utilize large-scale functional screens and detailed mechanistic studies to delineate the regulatory roles of these novel proteins in health and disease.

translational control and gene regulation

A fundamental question in biology is how the same set of protein synthesis machinery allow different transcripts to be differentially translated and regulated. By integrating genome-wide profiling techniques and biophysical tools, we examine the functions of trans-acting regulators (such as RNA-binding proteins and translation factors) as well as cis-regulatory elements in controlling translation, and how they are in turn regulated by intra- and extracellular environmental signals. Our goal is to discover novel translation mechanisms and determine why misregulation of translation leads to cancer and other diseases.

functional genomics and RNA architecture

Many major advances in modern biology have been driven by breakthrough biophysical techniques that enabled better control and quantitation of cellular phenomena. In our lab, we continue to develop tools to both perturb biological systems and measure the resulting cellular phenotype, including CRISPR-based techniques and massively-parallel, single-cell sequencing readouts. The long-term goal is utilize these technologies to understand the architecture and “information content” of RNA.

Past Funding

We thank the following for recognizing and funding our work:

CPRIT First Time Faculty Recruitment Award

Searle Scholar Award (Declined)

NIH K99/R00 Pathway to Independence Award

NIH DP2 New Innovator Award (Declined)

UT Southwestern Endowed Scholars Program in Medical Science