Thomas J. Wolpert
Thomas J. Wolpert was born and raised in eastern Nebraska. He received his B.S. degree in psychology with a minor in zoology from the University of Nebraska in 1973. After graduation, he worked in a number of jobs culminating in a position as a research technician in the laboratory of Dr. Larry Dunkle. Due to Dr. Dunkle’s tutelage, his interest in plant pathology was initiated, cultivated, and encouraged, resulting in his attending graduate school at Purdue University. He received his M.S. in plant physiology in 1979 and his Ph.D. in plant pathology in 1983. In that same year, he began a post-doctoral position in the laboratory of Dr. Vladimir Macko, an exceptional natural products chemist at the Boyce Thompson Institute, and worked on the structural characterization of the host-selective toxin victorin. At the end of 1989, he joined the Department of Botany and Plant Pathology at Oregon State University where he currently holds the rank of professor. His initial work with victorin coincided with the work of Dr. Noel Keen on the same pathosystem, resulting in numerous interactions. This experience led to a personal appreciation of the enormous scope and quality of Dr. Keen’s scientific contributions and Dr. Keen’s unique ability to simultaneously challenge, encourage, and collaborate in the pursuit of scientific excellence.
Dr. Wolpert is being honored with the Noel Keen Award for Research Excellence in Molecular Plant Pathology in recognition of his outstanding contributions toward understanding the structure/function of the host-selective toxin victorin. Made by the fungus Cochliobolus victoriae, this cyclized peptide induces rapid cell death in susceptible, victorin-sensitive oat cultivars, and is absolutely required for pathogenesis. The interaction between C. victoriae and oat represents one of the earliest examples of diseases where race specificity and host resistance could be attributed to a specific mechanism, namely an essential role in virulence for host-selective toxins. Dr. Wolpert has enormous enthusiasm for science and a tenacity that has proven essential in his search for new approaches and techniques in the face of very difficult problems that have surfaced during studies of this disease. His research has resulted in key contributions and seminal papers characterizing this host–pathogen interaction, and has garnered Dr. Wolpert and his colleagues national and international recognition in the area of molecular plant pathology.
The first of these accomplishments was achieved during his post-doctoral work with Dr. Macko, where in a collaborative effort, the structure of victorin was solved. This highly acclaimed accomplishment provided not only basic information about the long, sought-after structure of victorin, but it also enabled Dr. Wolpert and his colleagues to learn about reactive sites in the host through biochemical modifications of the molecule. Structural/functional characterization provided the means to tag the molecule at specific sites for studies of its binding to host proteins. This feat was accomplished where others over many decades had failed.
The identification of the proteins that bind victorin was another significant advance in the understanding of this complex problem. Initially, working with Dr. Macko, Dr. Wolpert demonstrated thata 100-kDa protein from oats specifically binds victorin. Subsequently, Dr. Wolpert and his students cloned and sequenced the cDNA for the 100-kDa protein and also for a 15-kDa protein that binds victorin. From these studies, they determined that the 100-kDa protein was the P protein (pyridoxal phosphate-containing enzyme) of the multienzyme glycine decarboxylase complex (GDC), and that the 15-kDa protein corresponded to the lipoamidecontaining enzyme or the H protein of the GDC. They also demonstrated that victorin was a potent inhibitor of GDC. These seminal efforts by Dr. Wolpert and his students resulted in a clean, unambiguous demonstration of the host proteins that bind victorin.
The characterization of victorin-binding proteins as components of the mitochondrial matrix presented the first indication that the probable mechanism by which victorin induces death in susceptible cultivars is not by a simple necrotic response, but through the induction of an apoptotic-like form of programmed cell death (PCD). A key feature in this discovery was the demonstration that victorin induces mitochondrial depolarization and additional specific events characteristic of PCD, such as the hallmark laddering effect of internucleosomal DNA cleavage and protease activation. In publications on this subject, Dr. Wolpert and his students were the first to demonstrate both in vivo and in vitro evidence for a mitochondrial permeability transition in plants and to characterize serine proteases that exhibit caspase-like activity. These phenomena are analogous to those observed in animal cells, where they play crucial roles during PCD. Dr. Wolpert’s studies also pointed to a new hypothesis that victorin interacts at a site of action upstream of binding to the GDC. Presently, he and his colleagues are defining the initiation phase of the PCD response with the hypothesis that the upstream site involves the product of the Vb gene, the oat gene that encodes sensitivity to victorin and susceptibility to disease.
In an effort to develop a genetic system for the identification of the upstream site of interaction of victorin, Dr. Wolpert and his colleagues conducted a large-scale screening effort of ecotypes of the model plant, Arabidopsis thaliana. Through this effort, victorin sensitivity was identified and found to be conferred, as in oats, by a single dominant gene designated LOV (for locus orchestrating victorin effects). Further, as in oats, this locus confers both victorin sensitivity and disease susceptibility to toxinproducing isolates of the fungus. The locus has been mapped, and efforts are underway to characterize both the LOV gene and additional loci required for victorin sensitivity. These efforts will undoubtedly lead to a clearer understanding of the mode-of-action of victorin and the implicit role of PCD in both disease resistance and susceptibility.
Beyond Dr. Wolpert’s studies of the molecular interactions that occur in Victoria blight of oats, he has published on studies involving toxins produced by Periconia circinata, Cephalosporium gramineum, and Pyrenophora tritici-repentis. His knowledge of fungal toxins is shared in close, professional interactions with numerous colleagues, and his work has been continuously supported by grants from the USDA/NRICGP and the NSF. Additionally, Dr. Wolpert teaches an undergraduate plant physiology course and a graduate course in plant microbe interactions. He is highly regarded as an advisor and mentor of graduate students.