1) Since 1996, my laboratory has also initiated a project to map the global structure of chromatin in situ using autofluorescent proteins as DNA markers. This approach open for the first time a window to the subnuclear architecture in live cells and should provide new understandings on the organization and dynamics of the biological information contained within chromosomes. We are also applying a fluorescent protein fusion tagging approach at a whole genome level with the aim of producing a collection of transgenic plant lines that will have most of the proteins in the genome tagged with a visible marker. These resources and novel technologies should provide an exciting opportunity to study subcellular organization of DNA and proteins at a global scale.

2) Another research program in my lab is in the area of programmed cell death, in terms of its mechanism of activation as well as its role in disease resistance. Programmed cell death (pcd) is a fundamental process that is recognized to occur in higher eukaryotes. Thus, during development of a multicellular organism, certain cells are destined to turnover in relatively predictable times and places. In addition, environmental and hormonal signals can also activate a cellular suicide program. Although pcd has been intensely studied in the past several years, particularly in mammalian cells and C. elegans, the actual mechanism through which eukaryotic cells commit suicide remains enigmatic. The current working hypothesis in this field is that the cellular machinery for pcd is present all the time in eukaryotic cells and is actively suppressed by certain proteins. Recently, we obtained evidence through inhibitor studies that caspases, a family of proteases that are conserved in animals as key regulators of pcd, are also likely to be involved in at least some cases of pcd in plants. This exciting finding suggests that the underlying mechanism for pcd may be conserved across plant and animal kingdoms. At the present time, my research focus in this area is directed at the elucidation of the molecular mechanisms involved in pcd and are currently engaged in the characterization of plant caspases. To this end, we have designed a novel detection technology for visualizing and tracking specific protease activities in living cells. This technology is currently being deployed to functionally clone the plant proteases that may be involved in controlling pcd. Ultimately, we would like to define the regulatory pathways through which caspases involved in HR-pcd are controlled.  This work should have broad impact on our understanding of how control of cellular suicide can be regulated to counter diseases as diverse as viruses and neurodegenerative disorders.

3) Transcription factors are nuclear proteins known to play an important role in stress responses and disease resistance.  Since 1987, we have been studying a conserved family of plant transcription factors called TGA proteins.  In the past several years, we and other laboratories have shown that these nuclear proteins are likely to function in signaling networks that can integrate information provided by at least three classes of phytohormones: auxins, jasmonic acid and salicylic acid.  More recently, physical interaction between specific members of this family of proteins and the disease resistance mediator NPR1 has been demonstrated to occur in yeast two-hybrid assays.  Suppression of detectable TGA activity by transgenic approach leads to an enhanced disease resistance phenotype.  This and other results suggested that the TGA factors likely function in a complex manner to regulate multiple genes in response to environmental signals.  Our current work focus on dissecting the role that each TGA gene may play by characterization of insertion “knockout” mutants of specific TGA genes in Arabidopsis as well as a novel dsRNA-directed gene silencing technique.  In addition, overexpression of individual TGA factor fusions with GFP has uncover a novel process of proteolytic control which appears to differentially regulate the steady-state level of these proteins.  We are also currently studying this process in more details using a combination of biochemical and molecular approaches.

Recent Publications
"Caspases and Programmed Cell Death in the Hypersensitive Response of Plants to Pathogens"  Olga del Pozo and Eric Lam (1998) Current Biol. 8, 1129-1132.

"Markers for Hypersensitive Response and Senescence Show Distinct Patterns of Expression"  Dominique Pontier, Susheng Gan, Richard M. Amasino, Dominique Roby and Eric Lam (1999) Plant Mol. Biol. 39, 1243-1255. “BAXing in the Hypersensitive Response”  Eric Lam, Olga del Pozo and Dominique Pontier (1999)  Trends in Plant Sci. 4, 419-421.  

“Die and Let Live - Programmed Cell Death in Plants”  Eric Lam, Dominique Pontier and Olga del Pozo (1999)  Curr. Op. in Plant Biol. 2, 502-507. “NPR1 Differentially Interacts with Members of the TGA/OBF Family of Transcription Factors Which Bind an Element of the PR-1 Gene Required for Induction by Salicylic Acid” Jun Ma Zhou, Youssef Trifa, Herman Silva,  Dominique Pontier, Eric Lam, Jyoti Shah and Daniel F. Klessig (2000)  Molecular Plant-Microbe Interations 13, 191-202.

“Nitric Oxide and Salicylic Acid Signaling in Plant Defense”  Daniel F.  Klessig, Jorg Durner, Robert Noad, Duroy A. Navarre, David Wendehenne, Dhirendra Kumar, Jun Ma Zhou, Jyoti Shah, Shuqun Zhang, Pradeep Kachroo, Youssef Trifa, Dominique Pontier, Eric Lam, and Herman Silva (2000)  Proc. Natl. Acad. Sci. USA 97, 8849–8855.

“Caspase-like Protease Involvement in the Control of Plant Cell Death”  Eric Lam and Olga del Pozo (2000)  Plant Mol. Biol. 44, 417-428.  

“Programmed Cell Death, Mitochondria and the Plant Hypersensitive Response” Eric Lam, Naohiro Kato and Michael Lawton (2001)  Nature 411, 848-853.  

“Specific Trans-dominant Suppression of Plant TGA Factors Reveals Complex Regulatory Functions in Plant Defense Reponses”  Dominique Pontier, Zhong-He Miao and Eric Lam (2001) Plant Journal, 27, 529-538.  

“Detection of Green Fluorescent Protein Tagged Chromosomes in Live Arabidopsis thaliana Plants”  Naohiro Kato and Eric Lam (2001) Genome Biology, in press. 

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