The NYU Langone Medical Center experienced an unprecedented storm on October 29th, 2012, causing damage that deeply impacted our patient care, research, and educational facilities. NYULMCs emergency power system was designed and built according to all safety codes to withstand a surge higher than the highest flood level for New York City in the past century. Superstorm Sandy obviously exceeded those levels. Although we safely evacuated over 300 patients in the midst of the storm, the extensive damage to its mechanical, electrical, and plumbing systems, required the temporary closure of our main campus. We are now in a post-disaster recovery period addressing the damage caused by the storm and assessing mitigation needs. NYU contains three basic science buildings, the Skirball Institute, the Smilow Research Center, and the Medical Science Building (MSB). The Gardner lab is located in the Smilow Research Center. However because Core laboratories, required for projects related to the grant, were located in MSB, the lab was also impacted by damage to MSB. The below-ground levels of Smilow Research Center and MSB, which included two vivarium facilities, were significantly damaged. The animal vivarium of Smilow was deemed completely Research Strategy Page 20 Principal Investigator/Program Director (Last, first, middle): Gardner, Lawrence, B unrecoverable. There was a complete loss of power, backup power, water and heat to these buildings for almost two weeks. Through the concerted efforts of literally hundreds of engineers and staff, the Smilow Research Center was re-opened by early January. However MSB sustained the most extensive damage, and repairs are ongoing. The restoration of MSB will result in a phased return of operations beginning this summer. For almost a month after the storm, the Smilow building was closed, elevators were not operational and gasoline fumes throughout the building limited the time we were able to safely visit the laboratory. However, we were able to make intermittent trips, carrying liquid nitrogen canisters to the 12th floor to try and salvage precious samples. All reagents that had been kept at -80 and -20 were lost. Most of our reagents at 4 degrees were lost, though some antibodies and restriction enzymes were still functional. Lost items include some commercial antibodies, serum, kits (e.g. glutathione, ATP, LDH), chemicals (e.g. reagents synthesized by Chembridge for our NMD inhibition experiments, detailed below), and spent several months generating, and protein lysates and RNA that were awaiting analyses. In addition, our laboratory is highly dependent on retroviruses and lentiviruses we generate. Generation of these viruses take several weeks and, depending on number of viruses placed in a cell and selection mechanism (e.g. FACS sorting or antibiotics), it can take several months to regenerate specific cell lines. Unfortunately, our manipulated growing cell lines, some of which we had were in the midst of generating over the previous several months with multiple lentiviruses were lost. Work requiring the Core laboratories (including FACS sorting, expression arrays, and mass spectroscopy) were significantly delayed by ~ 4 months. In addition, shipping and receiving were delayed, and critical experiments (detailed below) requiring radiation could not be completed While the laboratory was off limits, the PI was able to re-locate to an off-site office operated by the NYU Cancer Institute, where electricity had been restored and there was access to a computer. During this period the PI was able to continue with some work related to the grant, albeit at decreased productivity. Specifically, the PI analyzed data, completed drafts of four manuscripts related to the grant (one which is now in press, one has been accepted at MCB, one which is in Review, and one which is about to be submitted). Communication with lab personnel was initially hampered, as all email servers were non-functional for over a week after the storm. Eventually lab personnel supported by the grant assisted in bringing liquid nitrogen to the floor, but were not able to participate in experiments. Work initiated as part of a collaboration with the Rivella lab at Cornell University, which was unaffected by the storm, was continued. However, aspects of the project which required the ongoing generation of reagents from the Gardner lab could not be completed. Offers of assistance were received from others in the NYC Hematology community that were unaffected by the storm, including Jim Bieker from Mount Sinai. After the laboratory reopened in early January, all members of the laboratory (supported and not-supported by the grant) worked tireless to restore the laboratory, including testing and discarding destroyed reagents, sterilizing tissue culture hoods and incubators, re-ordering reagents, and regenerating cell lines which were destroyed. Experiments that were interrupted by the laboratory were re-initiated. It is estimated that in addition to the cost of reagents, approximately 2 month of ongoing studies were lost when the storm hit, the lab was not habitable for 1.0 months, and it required approximately 3 months to restore the lab (environment, reorder and generate commercial reagents, and re-generate cell lines), totaling 6 months. In addition, it took several more months to restore full efficiency. We still consider ourselves relatively lucky, since with the exception of one new chemical that had to be re-synthesized, our ruined reagents could be purchased commercially and/or regenerated within a few months, and we did not have long-term ongoing experiments (including mice who were generated) that perished in the storm. As of March, the laboratory is fully operational, at full productivity, and making good progress of continuing the experiments delineated in our initial proposal and revised in our yearly progress reports. Our productivity over the last four years of the grant is strong, resulting in 12 publications (9 as corresponding author), and have one article under review.
|Martin, L; Gardner, L B (2015) Stress-induced inhibition of nonsense-mediated RNA decay regulates intracellular cystine transport and intracellular glutathione through regulation of the cystine/glutamate exchanger SLC7A11. Oncogene 34:4211-8|
|Martin, Leenus; Grigoryan, Arsen; Wang, Ding et al. (2014) Identification and characterization of small molecules that inhibit nonsense-mediated RNA decay and suppress nonsense p53 mutations. Cancer Res 74:3104-13|
|Gold, Heidi L; Wengrod, Jordan; de Miera, Eleazar Vega-Saenz et al. (2014) PP6C hotspot mutations in melanoma display sensitivity to Aurora kinase inhibition. Mol Cancer Res 12:433-9|
|Wengrod, Jordan; Martin, Leenus; Wang, Ding et al. (2013) Inhibition of nonsense-mediated RNA decay activates autophagy. Mol Cell Biol 33:2128-35|
|Karam, Rachid; Wengrod, Jordan; Gardner, Lawrence B et al. (2013) Regulation of nonsense-mediated mRNA decay: implications for physiology and disease. Biochim Biophys Acta 1829:624-33|
|Gardner, Lawrence B (2010) Nonsense-mediated RNA decay regulation by cellular stress: implications for tumorigenesis. Mol Cancer Res 8:295-308|