|Division||Physical & Biological Sciences|
|Department||PBSci-Chemistry & Biochemistry Department|
|Web Site||Holman Research Web Site|
|Office Hours||Chem 1A: Tues & Wed 330-430, Chem 146B: By appointment. Group Meeting Tuesday, 12:30 PM to 2 PM|
|Campus Mail Stop||Chemistry|
|1156 High Street, 250 PSB|
Santa Cruz, CA
Role of Lipoxygenase in Inflammatory Diseases
Biochemistry is a fascinating and challenging discipline at the interface of biology and chemistry. Our research group utilizes enzymology, site directed mutagenesis, molecular biology and spectroscopy to investigate the biological function of enzymes from a rigorous chemical perspective. Specifically, we study the biological function of lipoxygenase (LOX). Soybean LOX is directly involved in soybean germination and senescence, while human LOX has been implicated in a variety of human diseases, such as asthma, heart disease, stroke and diabetes, to name a few. Therefore, LOX is a critically important enzyme in human health and the Holman laboratory endeavors to understand its enzymatic mechanism, discover novel inhibitors and investigate the role of LOX in human health.
There are six LOX isozymes and seven significant fatty acid substrates in the human body. The substrate specificity of each of the LOX isozymes varies from one to another, resulting in a complex array of LOX products being formed in human tissue. The Holman laboratory discovered that LOX products bind to an allosteric site on LOX, which changes the isozymes substrate specificity. This result is significant because it indicates that the distribution of LOX products can be modified, depending on the enzymatic activity of the six LOX isozymes and the available fatty acid substrates. The Holman laboratory is currently investigating the biochemical properties of the allosteric site and how it may be utilized to increase the production of beneficial LOX products.
Our lab is also interested in the discovery and characterization of novel inhibitors to lipoxygenase. We currently have discovered over 50 unique lipoxygenase inhibitors through screening the marine natural products library of our collaborator, Prof. Phil Crews and the NIH library with our collaborators at the NCGC (Dr. D. Maloney, Dr. A. Simeonov and Dr. A. Jadhav). We have screened these libraries with our high throughput lipoxygenase assay, which has increased our inhibitor discovery dramatically. These inhibitors are then investigated with biochemical and spectroscopic methods to determine how they bind and inhibit lipoxygenase.
The Holman laboratory utilizes the knowledge gained from their biochemical and inhibitory studies to probe LOX in human disease. Currently, the Holman laboratory investigates the role of LOX in Type-1 diabetes (Dr. J. Nadler), blood coagulation (Dr. M. Holinstat) and stroke (Dr. K. van Leyen). With these collaborations, the Holman laboratory hopes to contribute to the understanding of these important human diseases and possibly identify potent therapeutics.
Biography, Education and Training
B.A., University of California, San Diego
Ph.D., University of Minnesota, Minneapolis
Helen Hay Whitney Fellow, Harvard Medical School
Courses TaughtChem 1A: General Chemistry
Chem 151AL: Advanced Inorganic Chemistry
Chem 146B: Advanced Inorganic Chemistry laboratory
Chem 256B: Spectroscopy of bioinorganic molecules