Houfu Guo, PhD

Our lab is interested in studying how collagen-modifying enzymes and collagen post-translational modifications (PTMs) influence cell signaling and tissue homeostasis in health and diseases, such as cancer, connective tissue disorders, and fibrosis. Collagen is the most abundant protein in the animal kingdom. It forms the major component of the extracellular matrix to signal the cells and support cell survival, proliferation, migration, and differentiation. Collagen’s functions are tightly regulated by collagen PTMs of lysine residues. Loss or aberrant gain of collagen lysyl PTMs contributes to many inherited and acquired human diseases such as Ehlers-Danlos syndrome, Bruck syndrome, Epidermolysis bullosa like syndromes, cancer, and fibrotic diseases. The goals of our lab are to elucidate a structural basis for how collagen PTMs regulate the biochemical and biomechanical properties of diseased stroma and to gain a deeper understanding of how collagen PTMs contribute to injury response, cancer, connective tissue and fibrotic diseases. Our previous work has identified novel collagen PTMs, developed methods to express and assay these enzymes, and provided novel structural insights. We have also carried out small molecule library screens and identified bioactive compounds through collaborations. Going forward, we would like to continue our effort to gain structural insights into the key collagen-modifying enzymes (e.g. lysyl hydroxylase 2 or LH2) using structural biology techniques such as X-ray crystallography, to define the specific roles of collagen posttranslational modifications in connective tissue diseases, fibrosis, and cancer using a multi-disciplinary approach including biochemical and cellular assays and animal models, and to use these insights to develop knowledge-based therapeutics (e.g. LH2 antagonists). The Guo lab welcomes rotation students to participate in ongoing work on collagen-modifying enzymes and other collagen PTMs related projects. The students will learn protein biochemistry, cell biology, and animal modeling skills. Our lab has secured funding until the end of 2028 through an NIH/NCI R01 award (CA278989) and an American Cancer Society Research Scholar Grant (RSG-24-1156098-01-MM). https://uknow.uky.edu/research/markey-researcher-awarded-26-million-study-new-metastatic-lung-cancer-target?j=689121&sfmc_sub=251372416&l=21_HTML&u=27255717&mid=10966798&jb=4004