Campus Directory

Pronouns he, him, his, his, himself

Division Physical & Biological Sciences Division

Department/College/Unit Chemistry & Biochemistry Department

Title Professor

Affiliation Faculty

Faculty Type Regular Faculty

Areas of Expertise Biochemistry
Molecular Biology
Chemistry
Chemical Biology
Biomedical Sciences

Web Site

Primary Office Location Physical Sciences Building
250

Additional Location(s) Physical Sciences Bldg 250 (Office)
Physical Sciences Bldg 295/287 (Lab)

Office Hours TBA

Mail Stop Chemistry

Biography, Education and Training

B.A., University of California, San Diego
Ph.D., University of Minnesota, Minneapolis
Helen Hay Whitney Fellow, Harvard Medical School

Summary of Expertise

Biochemistry, bioinorganic chemistry, biophysics, enzymology, inhibitor discovery, and the role of fatty acid oxidation in human disease, such as stroke, diabetes and blood coagulation

Research Interests

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.

Allosteric Regulation:
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.

Inhibitor Discovery:
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. A. Simeonov and coworkers). 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.

Biological Relevance:
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.

Selected Publications

PubMed Listing of Prof. Holman's Publications

Courses Chem 1A: General Chemistry
Chem 4A: General Chemistry
Chem 151AL: Advanced Inorganic Chemistry
Chem 146B: Advanced Inorganic Chemistry laboratory