Gary retired from BTI in 2025.

Studies in the Blissard lab were focused on understanding the biology and pathology of viral infections and interactions in insect cells. In general, our studies can be subdivided into studies of a) baculovirus biology and pathology, b) viral envelope protein structure and function, and c) gene expression in virus infected cells.

The baculoviruses are large DNA viruses that have been used for biological control of insect pest species. In addition, baculoviruses have been developed as powerful gene expression systems for producing eukaryotic proteins in both research and industrial applications. More recently, baculoviruses have been examined as potential vectors for human gene therapy. One important thrust of our work is basic studies of the glycoproteins found in the virus envelope, and the roles of viral envelope proteins in viral attachment, entry, and exit. Another major research focus in our lab is the study of viral and host gene expression over the course of the infection. We are using next-generation sequencing technologies to examine the details of viral and host cell gene expression as infection progresses in baculovirus-infected insect cells, using both cultured cell lines and midgut tissue of host insects

Previously, we have used the baculovirus, AcMNPV, and the baculovirus GP64 envelope glycoprotein as models for our studies. We have developed AcMNPV-permissive cell lines to examine both viral envelope protein requirements, as well as cellular factors involved in entry and egress. Our recent studies suggest a model in which the promiscuous nature of baculovirus entry (which has been exploited in mammalian cell transduction systems) appears to result from recognition of, and interactions with negatively charged host membrane phospholipids. We found that this interaction appears to be mediated by specific regions of the so-called fusion loops of the major envelope glycoprotein, GP64. Our studies of GP64 have identified domains and specific amino acid positions important for virus-cell attachment, and we have also examined domains and amino acids required for the pH-triggered conformational change associated with membrane fusion during viral entry. Our studies of viral egress demonstrated that components of the cellular vacuolar protein sorting system (the cellular ESCRT pathway) are essential for baculovirus egress from infected cells. Thus, baculoviruses appear to hijack the cellular ESCRT pathway for egress from the cell.

In addition to the above studies, we are currently directing our efforts to the study of virus-insect interactions in the insect midgut. The polarized trafficking of viruses across this epithelial cell layer represents a critical virus-insect interaction that is essential for most insect-vectored viruses, but one that is not well understood in any system. Our studies focus on both identifying cellular interacting proteins and pathways that mediate polarized trafficking in the midgut, and understanding viral and cellular transcriptional responses in insect midgut cells from permissive and non-permissive hosts. We expect that our studies will have impacts on the understanding of pathogenic viruses of insects, as well as plant and animal viruses that are vectored by insects. In these studies, our goals are to generate new tools and methods for the study of the many viruses that traffic across the insect midgut epithelium.

Bob is a native of El Centro, California, a farming community located in the Imperial Valley of southern California. He obtained his B.S. degree from the University of California Davis Campus in 1960 and went on to graduate school at the University of Wisconsin, Madison where he obtained both a M.S. and PhD degree in Entomology in 1962 and 1964, respectively.

Bob joined the faculty of the Boyce Thompson Institute in Yonkers, NY in 1964 and remained at the Institute until he retired on December 31, 2002. His research career focused on the in vitro biology of insect cells and microbial control of insect pests. He published over 135 research papers, and co-edited three books in baculovirology and insect cell culture. He holds over 40 worldwide patents for his discoveries of insect virus pathogenicity genes and novel insect cell lines.

His pioneering research in insect cell culture resulted in the development of novel cell lines that proved exceptional as biotechnological tools for high expression of recombinant proteins useful in agriculture and medicine. This patented technology has been recognized worldwide and has been licensed to several companies. Other work involved the discovery of novel insect virus genes that have been patented and used to develop recombinant viruses with enhanced insect pesticidal activity, or have been engineered to make insect tolerant plants.

Bob also served the Institute as Director of the Plant Protection Program for 20 years. He received numerous honors during his career including: Fellow of the American Association for the Advancement of Science, Novartis National Recognition Award in Entomology, Fellow of the Academy of Microbiology, Fellow of the Society for In Vitro Biology, Fellow of the Entomological Society of America and President of the Society of Invertebrate Pathology. Bob was appointed to the Charles E. Palm Scientist Endowed Chair of BTI in 1992. He also holds a position as adjunct Professor of Entomology at Cornell University. He is currently consulting with the Institute as a Biotechnology Licensing and Marketing Associate in the Intellectual Property office.

Bob and his wife Johanna reside in Ithaca, NY.

A self-described “farmer from Wisconsin who raised pigs to put himself through college,” Dan discovered molecular biology as an undergraduate student in biochemistry at the University of Wisconsin during a lecture by Robert DeMar in 1969. “I knew then that molecular biology was what I wanted to do for the rest of my life,” he says.

Following completion of a master in molecular biology as a Marshall Scholar at the University of Edinburgh in 1973, Dan made his first significant scientific breakthrough as James Watson’s last graduate student at Harvard University and Cold Spring Harbor Laboratory (CSHL). It was there that Dan performed foundational research that culminated in the discovery of split genes and RNA splicing in human adenoviruses (1977 paper in Cell), which eventually won the Nobel Prize for Physiology or Medicine for his CSHL colleague Richard Roberts and Phillip Sharp of MIT.

While continuing to study adenoviruses until 1996, he initiated a research program in plant molecular biology in the early 1980’s, whose focus was to understand how plants protect themselves against microbial pathogens.  During the following decades, first at the Waksman Institute at Rutgers University (1985-2000) and then at BTI at Cornell University (2000-until retirement on 1/1/2022), he and his research team identified multiple components in pathways, which enable plants to recognize that they are being attacked and then rapidly mount defenses against the invader. Their efforts resulted in the identification of two critical defense-signaling molecules in plants – salicylic acid (SA) and nitric oxide (NO) (1998 paper in Proc Natl Acad Sci). Interestingly, both SA and NO also play roles in human health. NO is a potent endogenous signaling molecule in humans, where it plays critical roles in inflammatory and immune responses, in neural transmission, and in muscle physiology. Dan’s work demonstrated that several critical players of animal NO signaling are also operative in plants during their response to pathogen assault. Dan’s research group, together with colleague Ilya Raskin, discovered that SA is a key plant hormone that regulates immune responses (1990 paper in Science). Subsequent studies by Dan’s group identified the first mobile signal for systemic acquired resistance, which is a state of heightened defense that is activated throughout a plant after an initial local infection. This signal is methyl salicylate, a modified and inactive form of SA. Their research also revealed that, in contrast to most hormones in plants and animals, SA acts through, not one but, many different protein targets to mediate its many effects on immunity and other plant processes.

Interestingly, derivatives of SA have been used by humans for thousands of years to treat a variety of maladies. The prevailing view in the biomedical community has been that acetyl SA or aspirin, the most widely use drug worldwide for over a century, works primarily, if not exclusively, by irreversibly inhibiting the enzymatic activities of cyclooxygenases 1 and 2 (COX1 and COX2), However, aspirin is rapidly converted in the body to SA, which has similar pharmacological effects as aspirin, despite its poor ability to inhibit the cyclooxygenases. Dan’s  studies addressed this conundrum by discovering several novel targets through which SA mediates its many pharmacological effects, such as Glyceraldehyde 3-Dehydrogenase (GAPDH) and High Mobility Group Box1 (HMGB1) (e.g.,  2015 paper in Molecular Medicine, and  2016 paper in Frontiers in Immunology). HMGB1, when released outside of cells following tissue injury or secretion by certain immune or cancer cells, has potent pro-inflammatory activities associated with rheumatoid arthritis, atherosclerosis, inflammatory bowel disease, lupus, sepsis, inflammation-associated cancers and Alzheimer’s disease. GAPDH facilitates infection by the hepatitis viruses and is a major suspect in the neurodegenerative diseases Alzheimer’s, Parkinson’s, and Huntington’s. SA binds to both, thereby inhibiting their disease-associated activities. The identification of synthetic and natural derivatives of SA, which are 10-70 times more potent than SA at inhibiting GAPDH’s cell death-associated activities and HMGB1’s pro-inflammatory activities, provides proof-of-concept that better SA-based drugs can be obtained.

During the final decade of his research career, in collaboration with fellow BTI colleague Frank Schroeder, Dan made his last significant contribution to science. The pair found that small signaling molecules called ascarosides excreted by nematodes, tiny worms that live in the soil, induce plant immune responses which results in enhanced resistance against pathogens and pests (2015 paper in Nature Communications and  2020 paper in Nature Communications). This research led to the creation of a very successful Ag biotechnology company, Ascribe Bioscience, in which Dan remains actively involved.

During his long career, Dan mentored 82 postgrads from 18 countries, representing every continent except Antarctica, and published more than 200 research papers and 35 plus reviews and book chapters. He also provided administrative leadership, helping to revitalize two research institutes as Associate Director from 1985-2000 of the Waksman Institute and as President/CEO from 2000-2004 of BTI.

Alan received a Ph.D. from the Department of Plant Pathology at Purdue University and joined BTI in 1968. His graduate and early research at BTI included the first documentation of the divided genomes of component plant viruses.

In the early 70s, he studied the dsRNA viruses of plants and fungi in collaboration with Gert Streissle, Peter Day, and Robert Bozarth. During this time, he also collaborated with Lloyd Old’s group at the Sloan Kettering Cancer Institute on hybrid antibody research. During 1974-75, Alan was a Visiting Fellow with Bob Shepherd in the Department of Plant Pathology at UC Davis, developing techniques for the inoculation of plant protoplasts with cauliflower mosaic virus particles and DNA. From 1975 to 78, he was a member of the BTI Building Committee responsible for planning the BTI facility on the Cornell University campus.

From 1975 to 1996, his primary research interest was in the area of insect virology/pathology, developing the first insect-virus tissue-culture plaque assay techniques and the first viral-induced protein studies with baculoviruses. In the early 1980’s he began recombinant DNA studies with baculoviruses. On August 9, 1989, he performed the first U.S. field release of a recombinant virus, using a recombinant form of the Autographa baculovirus to control cabbage loopers, for which BTI got 5 minutes on the “Today” show. In 1993, a similar experiment was conducted for the U.S. Forest Service with a baculovirus to control gypsy moths. From 1989 to 1994, he chaired the Cornell University Recombinant DNA Committee and, in 1994, was appointed to the USDA Agricultural Biotechnology Advisory Committee. In 1993, together with Pat Hughes and Lee Compton (former BTI postdoc), he co-founded AgriVirion, Inc., a biotech company producing pharmaceutical proteins in larvae with the baculovirus expression vector system. AgriVirion merged with Chesapeake PERL Inc. in 2002.

From 1991 to 2001, Alan participated in collaborative research projects with Mike Shuler, Chair, Dept. of Chemical Engineering at Cornell. The original NSF research projects focused on optimization of insect cell culture bioreactors for the production of recombinant proteins and included Bob Granados. Later studies were conducted for NASA to elucidate the influence of gravity and various culture conditions on the eukaryotic glycosylation pathway. In April of 2001, he assumed the position of founding Director of the Life Sciences and Biotechnology Institute at Mississippi State University, where he was involved in research, teaching, and economic development. During 2003-04, at the invitation of the Secretary of Agriculture, he was a participant in an eight-member USDA Research, Education, and Economics Task Force, which wrote a report for the USDA and Congress recommending the formation of a National Institute for Food and Agriculture.