Active Projects

Structures of Protein Complexes Regulating Transcription in Embryonic Stem Cells

The major goal of this proposal is to reveal molecular mechanisms underlying formation and function of critical transcriptional assemblies essential to embryonic stem (ES) cells and cells with induced pluripotency (induced pluripotent stem (iPS) cells). The proposed structural and functional studies will propel our general knowledge of the basic mechanisms controlling cell fate, including those underlying self renewal, differentiation and pathogenesis of cancer, and would have a major impact on stem cell research as well as regenerative medicine.

This work is in concert with Paul Webb, The Methodist Hospital Research Institute, Houston, Bruce Conklin and Shinya Yamanaka, of the Gladstone Institute of Cardiovascular Disease, San Francisco and Ian Wilson, The Joint Center for Stuctural Genomics, La Jolla, CA.

NIH U01 GM094614, Consortia for High-Throughput-Enabled Structural Biology Partnerships. This program is part of NIH's Protein Structure Initiative: Biology Program

Selective thyroid hormone analogs for metabolic syndrome 

We plan to investigate biochemical and structural aspects of key NR/cofactor interactions that are obligate steps for maturation of the receptor complexes in the cytoplasm and their translocation into the nucleus and whether it will become possible to control receptor activity with small molecules that bind directly to receptor surfaces involved in these events.

NIH RC4 DK090849, subcontract with Paul Webb, TMHRI, Houston

Screening for antagonists of nuclear receptor LRH-1 in pancreatic cancer cells

We propose to discover selective inhibitors of LRH-1 activity that would arrest pancreatic cancer cell proliferation.

NIH R03 MH094165

Mechanisms of Regulation of LRH-1, Nanog and SF-1 by DAX-1 

The goal of this project is to understand the principles and atomic level details of the mechanisms of regulation of LRH-1 and SF-1 by DAX-1. Combined biochemical and structural analyses that we propose in this grant application will provide necessary information for understanding how LRH-1, SF-1, Dax-1 and Nanog function, how their activities are regulated, and how one could design and use specific modulators to tune aberrant activities hich underlie endocrine metabolic diseases and cancer. In addition, this work will show how we might elucidate the role of Dax-1 in regulating other transcription factors including TIF1, Rif1, Pelo, REST, Sall4, Sp1, Zfp609 and other nuclear receptors including Nur77, ERR2, ER, AR, HNF4 and GCNF.

NIH R01 DK078075 and NIH Diversity Supplement to Leslie Cruz, Graduate Student