OMB No. 0925-0046, Biographical Sketch Format Page



OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015)BIOGRAPHICAL SKETCHProvide the following information for the Senior/key personnel and other significant contributors.Follow this format for each person. DO NOT EXCEED FIVE PAGES.NAME:Robert J. Donnelly, Ph.D.POSITION TITLE:Director, New Jersey Medical School, Molecular Resource FacilityeRA COMMONS USER NAME (credential, e.g., agency login):RJDONNELLYEDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)INSTITUTION AND LOCATIONDEGREE(if applicable)Completion DateMM/YYYYFIELD OF STUDYSyracuseUniversity, Department of Biology, Syracuse, NY.WesleyanUniversity, Department of Biology, Middletown, CT.B.S.Ph.D05/197405/1985BiologyGeneticsLederle Laboratories, Department of Neurobiology, Pearl River, NYPostdoctoral03/1988Neurobiology/Molecular BiologyPersonal StatementI have been the Director of the Molecular Resource Facility for twenty years and have extensive experience with many molecular techniques including deep sequencing. My laboratory provides a wide range of services to the research community at New Jersey Medical School including high throughput DNA Sequencing, capillary DNA sequencing, oligonucleotide synthesis, quantitative PCR, peptide synthesis and sequencing, HPLC purifications and analysis, and various imaging capabilities. Currently the focus of the facility is high throughput DNA sequencing on each of the three instruments (SOLiD?, MiSeq? and Ion PGM?) that we are operating on a regular schedule. We also offer limited data analysis for the samples processed by our facility using commercially available software and instrument specific software provided by the manufacturers. As a result, I am well prepared to provide expertise in experimental design and interpretation of projects involving a variety of molecular approaches. I have been using the Luminex system for several years (see publications) and have experience with prior large scale cytokine analysis projects including: 1) several hundreds of human serum samples from a Chronic Fatigue Syndrome Study, 2) a study of patients with diabetic retinopathy involving 750 patients, 3) and a study of an autistic mouse model in which we analyzed cytokines in CSF, amniotic fluid and serum. As a result of the extensive experience with the Luminex system, I am well qualified to oversee the assay and analysis of a large sample volume on this platform. Nakamura T, Schwander SK, Donnelly R, Ortega F, Togo F, Broderick G, Yamamoto Y, Cherniack NS, Rapoport D, Natelson BH. (2010) HYPERLINK "" Cytokines across the night in chronic fatigue syndrome with and without Fibromyalgia.” Clin Vaccine Immunol. 2010 Feb 24.Nakamura, T., Schwander, S., Donnelly, R.J., Cook, D., Ortega, F., Togo, F., Yamamoto, Y., Cherniack, N., Klapholz, M., Rapoport, D., and Natelson, B. (2013) “Cytokines do not change after exercise or sleep deprivation in chronic fatigue syndrome” Clinical and Vaccine Immunology.Roy, M.S., Janal, M.N., Crosby, J.,Donnelly, R.J. (2013) “Inflammatory biomarkers and progression of diabetic retinopathy in African Americans with type 1 diabetes.” Invest Ophthalmol Vis Sci. 54. DOI:10.1167/iovs.13-12212.Roy, M.S., Janal, M.N., Crosby, J.,?Donnelly, R. (2014) “Markers of endothelial dysfunction and inflammation predict progression of diabetic nephropathy in African Americans with type 1 diabetes” Kidney International? 11?June?2014; doi: 10.1038/ki.2014.212.Mandal, M., Marzouk, A.C., Donnelly, R.J., Ponzio, N.M. (2010) Maternal immune stimulation during pregnancy affects adaptive immunity in offspring to promote development of TH17 cells. Brain, Behavior, and Immunity Available online 18 September 2010.Mandal M, Marzouk AC, Donnelly R, Ponzio NM. (2011) “ HYPERLINK "" Maternal immune stimulation during pregnancy affects adaptive immunity in offspring to promote development of TH17 cells.” Brain Behav Immun. 2011 Jul;25(5):863-71. Epub 2010 Sep. HYPERLINK "" Mandal, M., Donnelly, R., ? HYPERLINK "" Elkabes,?S., HYPERLINK "" Zhang, P.,? HYPERLINK "" Davini, D., ? HYPERLINK "" David,?B.T., HYPERLINK "" Ponzio, N.M.“ HYPERLINK "" Maternal immune stimulation during pregnancy shapes the immunological phenotype of offspring.” Brain Behavior and Immunity 05/2013.Positions and HonorsPositions and Employment1985-1987Associate Research Scientist, Department of Biology, Wesleyan University, Middletown, CT.1987-1988Postdoctoral Research Assistant, Central Nervous System Research Department, Lederle Laboratories, Pearl River, NY1988-1990Research Assistant Professor, Millhauser Laboratories, Department of Psychiatry, NYU Medical Center, NY, NY1990-1995Assistant Professor, Department of Molecular Genetics and Microbiology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ1995-PresentDirector, Molecular Resource Facility, UMDNJ-New Jersey Medical School, Newark, NJ1996-1998Assistant Professor, Department of Pathology and Laboratory Medicine, UMDNJ-New Jersey Medical School, Newark, NJ1998-2012Associate Professor, Department of Pathology and Laboratory Medicine, UMDNJ-New Jersey Medical School, Newark, NJ2010-PresentAdjunct Professor, Bioinformatics Program, School of Health Related Professions, UMDNJ, Newark, NJ (in July 2013 UMDNJ became part of Rutgers University)2000-PresentMember, Graduate School of Biomedical Sciences, UMDNJ, Newark, NJ (in July 2013 UMDNJ became part of Rutgers University)2012-PresentProfessor, Department of Pathology and Laboratory Medicine, UMDNJ-New Jersey Medical School, Newark, NJ (in July 2013 UMDNJ became part of Rutgers University)Contribution to ScienceIsolation of Two Alternative Forms of the Amyloid Precursor Protein.Alzheimer's disease (AD) is associated with the extra-normal accumulation of a 42 amino acid (aa) beta-amyloid peptide (BAP) in amyloid plaques and cerebrovascular deposits. Though BAP is deposited exclusively in brains of AD and Down syndrome patients, the mRNA encoding the putative precursor to BAP is found in the brain and in peripheral tissues. Using an HL 60 cDNA library, we isolated two Amyloid Peptide Precursor (APP) cDNAs with sequences that code for proteins containing 751 and 770 aa (APP 751 and APP 770). These longer forms of APP encode a novel region of 56 aa which is homologous to the Kunitz domain of serine protease inhibitors which is not found in the 695 aa form (APP 695) isolated from brain. We examined APP expression at the RNA level using Northern blots and S1 nuclease protection studies in which the lengths, distributions and relative abundances of APP RNAs were assayed. We found that brain, WA 17 cells and NG 108-15 cells contain all three forms of APP RNAs while HL 60 cells, TMT3 cells and AB-1 cells contain predominantly the APP 751 and APP 770 RNAs. These alternative forms of the APP have shown to be important in the pathology of Alzheimer’s Disease.Donnelly RJ, Friedhoff AJ, Beer B, Blume AJ, Vitek MP. Interleukin-1 stimulates the beta-amyloid precursor protein promoter. Cell Mol Neurobiol. 1990 Dec;10(4):485-95. PubMed PMID: 2091832.Goldgaber D, Harris HW, Hla T, Maciag T, Donnelly RJ, Jacobsen JS, Vitek MP, Gajdusek DC. Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7606-10. PubMed PMID: 2508093.Donnelly RJ, Jacobsen JS, Rasool CG, Blume AJ, Vitek MP. Isolation and expression of multiple forms of beta amyloid protein precursor cDNAs. Prog Clin Biol Res. 1989;317:925-37. PubMed PMID: 2481324.Donnelly RJ, Rasool CG, Bartus R, Vitek S, Blume AJ, Vitek M. Multiple forms of beta-amyloid peptide precursor RNAs in a single cell type. Neurobiol Aging. 1988 Jul-Aug;9(4):333-8. PubMed PMID: 2903459.Isolation of the Human Interferon Gamma Receptor.Interferon gamma (IFN-gamma) signals through a multimeric receptor complex consisting of two different chains: the IFN-gamma receptor binding subunit (IFN-gamma R, IFN-gamma R1), and a transmembrane accessory factor (AF-1, IFN-gamma R2) necessary for signal transduction. Using cell lines expressing different cloned components of the IFN-gamma receptor complex, we examined the function of the receptor components in signal transduction upon IFN-gamma treatment. A specific IFN-gamma R2:IFN-gamma cross-linked complex was observed in cells expressing both IFN-gamma R1 and IFN-gamma R2 indicating that IFN-gamma R2 (AF-1) interacts with IFN-gamma and is closely associated with IFN-gamma R1. We showed that the intracellular domain of IFN-gamma R2 is necessary for signaling. Cells coexpressing IFN-gamma R1 and truncated IFN-gamma R2, lacking the COOH-terminal 51 amino acids (residues 286-337), or cells expressing IFN-gamma R1 alone were unresponsive to IFN-gamma treatment as measured by MHC class I antigen induction. Jak1, Jak2, and Stat1 alpha were activated, and IFN-gamma R1 was phosphorylated only in cells expressing both IFN-gamma R1 and IFN-gamma R2. Jak2 kinase was shown to associate with the intracellular domain of the IFN-gamma R2.Soh J, Donnelly RJ, Mariano TM, Cook JR, Schwartz B, Pestka S.? HYPERLINK "" Identification of a yeast artificial chromosome clone encoding an accessory factor for the human interferon gamma receptor: evidence for multiple accessory factors.?Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8737-41. PubMed PMID: 8378357. Soh J, Donnelly RJ, Kotenko S, Mariano TM, Cook JR, Wang N, Emanuel S, Schwartz B, Miki T, Pestka S.? HYPERLINK "" Identification and sequence of an accessory factor required for activation of the human interferon gamma receptor.?Cell. 1994 Mar 11;76(5):793-802. PubMed PMID: 8124716.Cleary CM, Donnelly RJ, Soh J, Mariano TM, Pestka S.? HYPERLINK "" Knockout and reconstitution of a functional human type I interferon receptor complex.?J Biol Chem. 1994 Jul 22;269(29):18747-9. PubMed PMID: 8034627. Kotenko SV, Izotova LS, Pollack BP, Mariano TM, Donnelly RJ, Muthukumaran G, Cook JR, Garotta G, Silvennoinen O, Ihle JN, et al.? HYPERLINK "" Interaction between the components of the interferon gamma receptor complex.?J Biol Chem. 1995 Sep 8;270(36):20915-21. PubMed PMID: 7673114.Identification of the LINCL gene. Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal neurodegenerative disease. A molecular basis for LINCL was determined with an approach applicable to other lysosomal storage diseases. When the mannose 6-phosphate modification of newly synthesized lysosomal enzymes was used as an affinity marker, a single protein was identified that is absent in LINCL. Sequence comparisons suggest that this protein is a pepstatin-insensitive lysosomal peptidase, and a corresponding enzymatic activity was deficient in LINCL autopsy specimens. Mutations in the gene encoding this protein were identified in LINCL patients but not in normal controls. To understand the molecular pathology of LINCL, we conducted a genetic survey of CLN2 in 74 LINCL families. In 14 patients, CLN2 protease activities were normal and no mutations were identified, suggesting other forms of NCL. Both pathogenic alleles were identified in 57 of the other 60 LINCL families studied. In total, 24 mutations were associated with LINCL, comprising six splice-junction mutations, 11 missense mutations, 3 nonsense mutations, 3 small deletions, and 1 single-nucleotide insertion. An Arg-->His substitution was identified, which was associated with a late age at onset and protracted clinical phenotype, in a number of other patients originally diagnosed with juvenile NCL.Sleat DE, Donnelly RJ, Lackland H, Liu CG, Sohar I, Pullarkat RK, Lobel P.? HYPERLINK "" Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis.?Science. 1997 Sep 19;277(5333):1802-5. PubMed PMID: 9295267.Liu CG, Sleat DE, Donnelly RJ, Lobel P.? HYPERLINK "" Structural organization and sequence of CLN2, the defective gene in classical late infantile neuronal ceroid lipofuscinosis.?Genomics. 1998 Jun 1;50(2):206-12. PubMed PMID: 9653647.Sleat DE, Gin RM, Sohar I, Wisniewski K, Sklower-Brooks S, Pullarkat RK, Palmer DN, Lerner TJ, Boustany RM, Uldall P, Siakotos AN, Donnelly RJ, Lobel P.? HYPERLINK "" Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder.?Am J Hum Genet. 1999 Jun;64(6):1511-23. Erratum in: Am J Hum Genet. 2004 Dec;75(6):1158. PubMed PMID: 10330339; PubMed Central PMCID: PMC1377895.The New Jersey Medical School Molecular Resource Facility. As director of the New Jersey Medical School Molecular Resource Facility I have had the privilege of being involved in many important and exciting research programs with the faculty at NJMS as well as other institutions. Complete List of Published Work in MyBibiliography: HYPERLINK "" \t "_blank" SupportNo direct externally funded projects. As a core director, I am a consultant on many grants to faculty of the medical school.Pending:U24 “Molecular Transducers of Physical Activity in Humans Consortium (MoTrPAC)”Role: Cytokine Core Director, PI’s: Drs. Hong Li (Contact, PI, Rutgers-NJMS) and David Feny? (NYUMC) Please refer to the Biographical Sketch sample in order to complete sections A, B, C, and D of the Biographical Sketch. ................
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