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Robbins Lab

The pathways important for driving autoimmune and inflammatory diseases as well as age related degeneration are surprisingly similar. For example, inhibition of the transcription factor NF-κB is therapeutic in mouse models of autoimmunity and inflammation as well as Duchenne muscular dystrophy and aging. Similarly, inhibition of IL-1ß signaling by gene transfer of the IL-1 receptor antagonist protein is therapeutic in multiple models of diseases. The Robbins laboratory is developing novel approaches to treat autoimmune (type 1 diabetes, rheumatoid arthritis), inflammatory (inflammatory bowel disease, delayed type hypersensitivity) and age-related degenerative diseases using biologics and small molecules. The therapeutic approaches being developed include: 1) AAV mediated gene transfer of anti-inflammatory or immunosuppressive agents; 2) Peptide and small molecule inhibitors of the transcription factor of NF-κB; 3) Novel osteogenic peptides; 4) Adult stem cells; 5) Microvesicles (exosomes) derived from immunoregulatory or stem cells able to block inflammation or promote regeneration; and 6) Identification of drugs able to reverse cellular senescence for improving healthy aging. Although the majority of the studies are being performed in mouse models of disease, approaches to treat osteoarthritis by intra-articular AAV-mediated gene transfer and Duchenne muscular dystrophy by systemic treatment with a NF-κB inhibitory peptide will soon be entering the clinic.

 

Lab Members:

Ralph Flores

Post-Doc

Education:

B.S., Biology- University of Texas of San Antonio, 1993

PH.D., Immunology-University of Pittsburgh, 2005

Fernando Santiago

Post-Doc

Education:

B.S., Biology, University of Georgia, 2001

Ph.D. Neuroscience & Cognition, Universidade Federal do ABC, 2015

 

Lei Zhang

Post-Doc

Education:

B.S. Engineering, Beijing Institute of Technology, China, 2005

Ph.D Medicinal Chemistry and Drug Design, Shanghai Institute of Materia Medica, 2012

 

Research Areas:

The Robbins laboratory is developing novel approaches to treat autoimmune (type 1 diabetes, rheumatoid arthritis), inflammatory (inflammatory bowel disease, delayed type hypersensitivity) and age-related degenerative diseases using biologics and small  molecules. The therapeutic approaches being developed include: 

1) AAV mediated gene transfer of anti-inflammatory or immunosuppressive agents.  Here we are using AAV-mediated gene transfer to endogenous islets of NOD mice (see figure below) to prevent onset of type I diabetes. We also are using AAV-mediated gene transfer to joints to treat rheumatoid and osteoarthritis. We previously performed a gene therapy trial for rheumatoid arthritis using synovial fibroblasts genetically modified to expressing IL-1Ra as outlined below. A clinical study using AAV-mediated gene transfer of IL-1Ra for treatment of osteoarthritis will be initiated in 2014.

Systemic Inection of AAV8-eGFP results in infection of Endogenous Murine Islets

Schematic of the first phase I clinical trial for rheumatoid arthritis

2) Development of peptide and small molecule inhibitors of the transcription factor of NF-κB for treating inflammatory and degenerative diseases.  We have developed a fusion peptide containing a protein transduction domain fused to a peptide (NBD) able to disrupt the kinase (IKK) important for inducing the activity of NF-κB. This peptide is highly therapeutic in mouse models of autoimmune, inflammatory and degenerative diseases including aging. We currently are developing small molecule mimetics of the NBD peptide for clinical use. Also, as shown below, we are examining the upregulation of NF-κB transcriptional activity with aging using a transgenic mouse carrying a NF-κB dependent promoter-eGFP reporter.  Using this reporter mouse model, we have demonstrated that NF-κB is activated in a stochastic manner with aging.

3) Development of novel osteogenic peptides. We have demonstrated that certain isoforms of the intracellular Lim Mineralization Protein (LMP) is highly osteogenic following gene transfer.  We are currently mapping the osteogenic domain(s) of LMP in order to develop peptides able to induce osteogenesis following protein transduction mediated delivery.  As shown below, gene transfer of LMP to muscle results in efficient ectopic bone formation.

4) Aging of adult stem cells.  We have demonstrated previously that function and number of adult stem cell populations decline with aging.  Interestingly, injection of functional adult stem cells into a mouse model of accelerated aging extended lifespan and healthspan through an apparent endocrine/paracrine mechanisms (see figure below).  We currently are examining approaches to improve the function of aged stem cells as well as identify the therapeutic factors secreted by functional stem cells.

5) Therapeutic applications of microvesicles (exosomes).  Exosomes are a type of secreted membrane vesicles produced by a large variety of cell types. They are characterized by an endocytic origin, formed by the reverse budding of the multivesicularbodies and have a size of around 30-100 nM in diameter (see figure below). Their protein content largely reflects those of the parental cells and is enriched in certain molecules including proteins and miRNA.  We have demonstrated that dendritic cell-derived exosomes can be highly immunosuppressive, able to reverse established autoimmune disease.  We currently are examining the mechanism of immunosuppression of antigen-presenting cell derived as well as tumor-derived exosomes.  Similarly, we are examining the possible role of exosomes in regulating aging.  

6) Identification of pathways important for cellular senescence.   Cellular senescence has been linked to both aging and cancer.  We have demonstrated that inhibition of certain pathways or factors (mTOR, NF-κB, ROS) can prevent or reverse senescence (see figure below).  We currently are developing approaches to screen for drugs that can reverse DNA damage-induced cellular senescence. The drugs identified as reversing senescence will then be tested for ability to extend lifespan and healthspan in a mouse model of accelerated aging.

 

Publications:

2009

Bianco, N., Kim, S.-H., Ruffner, M. and Robbins, P. D. (2009) Therapeutic effect of exosomes from indoleamine 2,3-dioxygenase positive dendritic cells in collagen-induced arthritis and delayed-type hypersensitivity disease models. Arthritis Rheum. 60:380-9. PMC3491653. PubMed Link

Evans, C. H., Ghivizzani, S. C. and Robbins, P. D. (2009) Gene Therapy of the Rheumatic Diseases: 1998-2008. Arthr. Rheum. & Ther. 11:209, PMC2688220. PubMed Link

Evans, C. H., Ghivizzani, S. C., and Robbins, P. D. (2009) Orthopaedic gene therapy in 2008. Mol. Ther. 17:231-44. PMC2835052. PubMed Link

Evans, C. H., Ghivizzani, S. C., and Robbins, P. D. (2009) Progress and prospects: genetic treatments for disorders of bones and joints. Gene Ther. 16:944-52. PMID: 19675584 PubMed Link

Jeong, M., Kwon, Y.-S., Park, S.-H., Kim, C.-Y., Jeun, S.-S., Song, K.-W., Ko, Y., Robbins, P. D., Billiar, T. and Kim, B.-M. (2009) Possible novel therapy for malignant gliomas with secretable trimeric TRAIL. PLoS ONE 4:4545. PMC2641005. PubMed Link

Kay, J. D., Gouze, E., Oligino, T. J., Gouze, J. N., Watson, R. S., Levings, P. P., Bush, M. L., Dacanay, A., Nickerson, D. M., Robbins P. D., Evans, C. H., and Ghivizzani, S. C. (2009) Intra-articular gene delivery and expression of IL-1Ra mediated by self complementary adeno-associated virus. J. Gene Med. 11:605-14. PMC2876984. PubMed Link

Lefèvre, S., Knedla, A., Tennie. C., Kampmann, A., Wunrau, C., Dinser, R., Korb, A., Schnäker, E. M., Tarner, I. H., Robbins, P. D., Evans, C. H., Stürz, H., Steinmeyer, J., Gay, S., Schölmerich, J., Pap, T., Müller-Ladner, U.,and Neumann, E. (2009) Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nat. Med. 15:1414-1420. NIHMS468594. PubMed Link

Reay, J., Kim, S.-H., Lockhart, E., Kolls, J. K., and Robbins, P. D. (2009) Adenoviral mediated, intratumor gene transfer of interleukin 23 induces a therapeutic antitumor response. Cancer Gene Ther. 16:776-85. PMC2745505.  PubMed Link

Ruffner, M. A., Kim, S. H., Bianco, N. R., Francisco, L. M., Sharpe, A. H. and P. D. Robbins. (2009) B7-1/2, but not PD-L1/2 molecules, are required on IL-10-treated tolerogenic DC and DC-derived exosomes for in vivo function. E. Jour. Immunol. 39:3084-3090. PMC3075967. PubMed Link

Wehling, P., Reinecke, J., Baltzer, A. W., Granrath, M., Schulitz, K. P., Schulz, C., Krauspe, R., Whiteside, T. W., Elder, E., Ghivizzani, S. C., Robbins, P. D. and Evans, C. H. (2009) Clinical responses to gene therapy in joints of two subjects with rheumatoid arthritis. Human Gene Ther. 20:97-101. PMC2855248. PubMed Link

2010

Bernardini, C., Saulnier, N., Parrilla, C., Pola, E., Gambotto, A., Michetti, F., Robbins, P. D., and Lattanzi, W. (2010) Early transcriptional events during osteogenic differentiation of human bone marrow stromal cells induced by Lim Mineralization Protein 3. Gene Expr. 15:27-42. PMID21061915. PubMed Link

Chernajovsky, Y. and Robbins, P. D (2010) Perspectives for the future developments of gene therapy for autoimmune and inflammatory therapy, in Gene Therapy for Autoimmune and Inflammatory Diseases, Chernajovsky and Robbins, Eds.

Gaddy, D. F., Riedel, M. J., Pejawar-Gaddy, S., Kieffer, T. J, and P. D. Robbins. (2010) In vivo expression of HGF/NK1 and GLP-1 From dsAAV vectors enhances pancreatic ß-cell proliferation and improves pathology in the db/db mouse model of diabetes. Diabetes 59:3108-3016. PMC2992772. PubMed Link

Gaddy, D. F., Ruffner, M. A. and Robbins, P. D. (2010) Gene therapy for autoimmune disorders. In A Guide to Human Gene Therapy, R. Herzog and S. Zolotukhin, eds.

Ghosh, H. S., McBurney, M. and Robbins, P. D. (2010) Sirt1 negatively regulates the mammalian target of rapamycin. PLoS ONE 5:e9199. PMC2821410. PubMed Link

Rehman, K. K. and Robbins, P. D. (2010) Comparison of Functional Protein Transduction Domain Delivery using the Nemo Binding Domain Peptide. Pharmaceuticals 3:110-124.

Riedel, M., Gaddy, D. F., Asadi, A., Robbins, P. D. and T. Kieffer. (2010) dsAAV8-Mediated Expression of Glucagon-like Peptide-1 in Pancreatic Beta Cells Ameliorates Streptozotocin-Induced Diabetes. Gene Ther. 17:171-80. PMID19865180. PubMed Link

Ruffner, M. A. and Robbins, P. D. (2010) Dendritic cells transduced to express interleukin 4 reduce diabetes onset in both normoglycemic and prediabetic nonobese diabetic mice. PLoS ONE 5:e1184. PMC2912295. PubMed Link

Tang, Y., Reay, D. P., Salay, M. N., Mi, M. Y., Clemens, P. R., Guttridge, D. C., Robbins, P. D., Huard, J., and Wang, B. (2010) Inhibition of the IKK/NF-kB Pathway by AAV Gene Transfer Improves Muscle Regeneration in Older mdx Mice. Gene Ther. 17:1476-83. PMC3471137. PubMed Link

Vo, N., Seo, H.-Y., Robinson, A. R., Sowa, G., Studer, R., Bentley, D., Taylor, L., Usas, A., Alber, S., Huard, J., Watkins, S. C., Lee, J., Coehlo, P., Wang, D., Loppini, M., Robbins, P. D., Niedernhofer, L. J., and J. Kang (2010) Accelerated aging of intervertebral discs in a mouse model of progeria. J. Ortho. Res. 28:1600-7. PMC3477798. PubMed Link

Zahid, M., Lu, X., Mi, Z. and Robbins, P. D. (2010) Cationic and tissue-specific protein transduction domains identification, characterization, and therapeutic application. Adv Genet. 69:83-95. PMID: 20807603 PubMed Link

Zahid, M., Phillips, B. E., Albers. S. M, Giannoukakis, N., Watkins, S. C. and Robbins, P.D. (2010) Identification of a cardiac specific protein transduction domain by in vivo biopanning using a M13 phage peptide display library in mice. PLoS One 5:e12252. PMC2923200.  PubMed Link

 2011

Evans, C. H., Ghivizzani, S. C. and Robbins, P. D. (2011) Getting arthritis gene therapy into the clinic. Nat. Rev. Rheum. 7:244-9. PMC3460537. PubMed Link

Gaddy, D. F., Riedel, M. J., Bertera, S., Kieffer, T. J, and P. D. Robbins. (2011) DsAAV8-mediated gene transfer and ß-cell expression of IL-4 and β-cell growth factors is capable of reversing early-onset diabetes in NOD mice. Gene Ther. 19:791-9. PMID22089495. PubMed Link

Gatson, N. N., Williams, J. L., Powell, N. D., McClain, M. A., Hennon, T. R., Robbins, P. D. and Whitacre, C.C. (2011) Induction of pregnancy during established EAE halts progression of CNS autoimmune injury via pregnancy-specific serum factors. J Neuroimmunol. 230:105-13. PMC3021646. PubMed Link

Ghosh, H., Reizis, B., and Robbins, P. D. (2011) SIRT1 associates with eIF2-alpha and regulates the cellular stress response. Sci Rep. 1:150. PMC3252071. PubMed Link

Goss, J. R., Beer-Stolz, D., Robinson, A. R., Zhang, M., Arbujas, N., Robbins, P. D., Glorioso, J. C. and L. J. Niedernhofer. (2011) Premature Aging-related Peripheral Neuropathy in a Mouse Model of Progeria. Mech Ageing Dev. 132:437-42. PMC3179831. PubMed Link

Kim, C. Y., Park, S. H., Jeong, M., Kwon, O. S., Doh, H., Kang, S. H., Robbins, P. D., Kim, B. M., Seol, D. W. and Kim, B. G. (2011) Preclinical studies for pharmacokinetics and biodistribution of Ad-stTRAIL, an adenovirus delivering secretable trimeric TRAIL for gene therapy. Exp Mol Med. 43:580-6. PMC3222819. PubMed Link

Niedernhofer, L. J., Glorioso, J. C., and Robbins, P. D. (2011) Dedifferentiation rescues senescence of progeria cells but only while pluripotent. Stem Cell Res Ther 2:28. PMC3152996. PubMed Link

Peterson, J. M., Kline, W., Canan B., Ricca, D., Kaspar, B., Delfin, D. A., DiRienzo, K., Clemens, P. Robbins, P. D., Baldwin, A. S., Lood, P., Frietas, M., Kornegay, J., Mednell, J. R., Rafael-Fortney, J. A., Guttridge, D. C., and Janssen, P. M. L. (2011) Peptide-based inhibition of NF-ΚB rescues diaphragm muscle contractile dysfunction in a murine model of Duchenne muscular dystrophy. Mol. Med. 17:508-15. PMC3105127. PubMed Link

Pola, E., Nasto, L. A., Tampieri, A., Lattanzi, W., Di Giacomo, G., Colangelo, D., Ciriello, V., Pagano, E., Spinelli, S., Robbins, P. D., Logroscino, G. (2011) Bioplasty for vertebral fractures: preliminary results of a pre-clinical study on goats using autologous modified skin fibroblasts. Int J Immunopathol Pharmacol 24(1 Suppl 2): 139-142. PMC3512194. PubMed Link

Reay, D. P., Yang, M., Watchko, J. F., Daood, M., O’Day, T. L., Rehman, K. K., Guttridge, D. C., Robbins, P. D. and Clemens, P. R. (2011) Systemic delivery of NEMO binding domain/IKKgamma inhibitory peptide to young mdx mice improves dystrophic skeletal muscle histopathology. Neurobiol Dis. 43:598-608. PMC3145633. PubMed Link

Tilstra, J. S., Clauson, C. L., Niedernhofer, L. J. and Robbins, P. D. (2011) NF-ΚB in aging and disease. Aging Dis., 2:449-465 PMC3295063. PubMed Link

Yang, C., Kim, S.-H, Bianco, N. R. and Robbins, P. D. (2011) Tumor-Derived Exosomes Confer Antigen-Specific Immunosuppression in a Murine Delayed-Type Hypersensitivity Model. PLoS ONE 6:e22517. PMC3149056. PubMed Link

Yang, C., and Robbins, P. D. (2011) The roles of tumor-derived exosomes in cancer pathogenesis. Clin. Dev. Immunol. 2011:842849 PMC3235485. PubMed Link

Zahid, M. and Robbins, P. D. (2011) Identification and characterization of tissue-specific protein transduction domains using peptide phage display. Methods Mol Biol. 683:277-89. PMID: 21053137 PubMed Link

2012

Barba, M., Pirozzi, F., Saulnier, N., Vitali, T., Natale, M. T., Logroscino, G., Robbins, P. D., Gambotto, A., Neri, G., Michetti, F., Pola, E., and Lattanzi, W. (2012) Lim Mineralization Protein 3 induces the osteogenic differentiation of Human Amniotic Fluid Stromal Cells through Kruppel-like Factor-4 down-regulation and further bone-specific gene expression. J. Biomed. Biotech., 2012:813894. Doi: 10.1155-2012-813894. PMC3471036. PubMed Link

Evans, C. H., Ghivizzani, S. C. and Robbins, P. D. (2012) Orthopaedic Gene Therapy - Lost in Translation. J Cell Physiol. 227:416-20. PMC3264489. PubMed Link

Lavasani, M., Robinson, A. R., Lu, A., Song, M., Feduska, J. M., Ahani, B., Tilstra, J. S., Feldman, C. H., Robbins, P. D., Niedernhofer, L. J., and Huard, J. (2012) Muscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model. Nat. Commun. 3:608. doi: 10.1038/ncomms1611. PMC3272577. PubMed Link

Lin. Z., Rios, H. F., Park, C.-H., Taut, A., Jin, Q., Sugai, J. V., Robbins, P. D. and W. V. Giannobile. (2012) Lim domain protein-3 (LMP) cooperates with BMP-7 to promote tissue regeneration by ligament progenitor cells. Gene Ther. 20:1-6. PMC3330200. PubMed Link

Lu, A., Proto, J., Guo, L., Tang, Y., Lavasani, M., Tilstra, J. S., Wang, B., Guttridge, D. C., Niedernhofer, L. J., Robbins, P. D. and J. Huard. (2012) NF-ΚB negatively impacts the myogenic potential of muscle-derived stem cells. Mol. Ther. 20:661-8. PMC3293604 PubMed Link

Nasto, L. A., Seo, H.-Y., Robinson, A. R., Tilstra, J. S., Clauson, C. L., Sowa, G. A., Ngo, K., Dong, Q., Pola, E., Lee, J. Y., Niedernhofer, L. J., Kang, J. D., Robbins, P. D. and N.V. Vo (2012) Inhibition of NF-ΚB activity ameliorates age-associated disc degeneration in a mouse model of accelerated aging. Spine, 37:1819-25. PMC3395770 *awarded as the best biology manuscript by the International Society for the Study of the Lumbar Spine (ISSLS) PubMed Link

Reay, J., Gambotto, A. and Robbins, P. D. (2012) The antitumor effects of adenoviral-mediated, intratumoral delivery of interleukin 23 require endogenous IL-12. Cancer Gene Ther., 19:135-43. PMC3508719. PubMed Link

Tilstra, J. S., Robinson, A. R., Wang, J., Gregg, S. Q., Clauson, C. L., Reay, D. P., Nasto, L. A., St. Croix, C.M., Usas, A., Vo, N., Huard, J., Clemens, P. R., Stoltz, D. B., Guttridge, D. C., Watkins, S. C., Garinis, G. A., Wang, Y., Niedernhofer, L. J., and P. D. Robbins. (2012) NF-kB inhibition delays DNA damage-induced senescence and aging in mice. J. Clin. Invest. 122:2601-12. PMC3386805. PubMed Link

Wang, J., Clauson, C. L.., Robbins, P. D., Niedernhofer, L. J., Wang, Y. (2012). The oxidative DNA lesions 8,5'-cyclopurines accumulate with aging in a tissue-specific manner. Aging Cell 11:714-16. PMC3399950. PubMed Link

Xun, Z., Rivera-Sanchez, S., Ayala-Pena, S., Lim, J., Budworth, H., Skoda, E. M., Robbins, P. D., Niedernhofer, L. J., Wipf, P., McMurray, C. T. (2012) Targeting of XJB-5-131 to mitochondria suppresses oxidative DNA damage and motor decline in a mouse model of Huntington’s disease. Cell Rep., 2:1137-42, PMC3513647. PubMed Link

Yang, C., Chalasani, G., Ng, W.-H, and Robbins, P. D. (2012) Exosomes released from Mycoplasma infected tumor cells activate inhibitory B cells. PLoS ONE 7:e36138. PMC3338602. PubMed Link

Yang, C. and Robbins, P. D. (2012) Immunosuppressive exosomes: a new approach fortreating arthritis. Int J Rheumatol. 2012:573528, PMC3324137. PubMed Link

Yang, C., Ruffner, M. A., Kim, S.-H., and Robbins, P. D. (2012) Plasma-derived MHC class II+ exosomes from tumor-bearing mice suppress tumor antigen-specific immune responses. Eur. J. Immunol. 42:1778-84. PMC3471134. PubMed Link

Zahid, M. and Robbins, P. D. (2012) Protein transduction domains: applications for molecular medicine. Curr Gene Ther. 12:374-80, PMID: 22920684. PubMed Link

2013

Chen, Q., Liu, K., Robinson, A. R., Clauson, C. L., Blair, H. C., Robbins, P. D., Niedernhofer, L. J. and Ouyang, H. (2013) DNA damage drives accelerated bone aging via an NF-kB dependent mechanism. J. Bone Min. Res., 28:1214-28. PMC3662975.  PubMed Link

Dorronsoro, A., and Robbins, P. D. (2013) Regenerating the injured kidney with human umbilical cord mesenchymal stem cell derived exosomes.  Stem Cell Res. Ther. 4:39. PMID: 23680102. PubMed Link

Evans, C. H., Ghivizzani, S. C. and Robbins, P. D. (2013) Arthritis gene therapy and its tortuous path into the clinic. Transl Res. 161:205-16. Doi: 10.1016/j.trsl.2013.01.002. Epub 2013 Jan 29. PMC3602127. PubMed Link

Lavasani, M., Lu, A., Thompson, S.D., Robbins, P.D., Huard, J., and L.J. Niedernhofer (2013) "Isolation of muscle-derived stem/progenitor cells based on adhesion characteristics to collagen-coated surfaces", in Methods in Molecular Biology ed. K. Turksen, Springer. 2013;976:53-65. Doi: 10.1007/978-1-62703-3176_5. PMID: 23400434, NIHMS491012. PubMed Link

Nasto, L. A., Robinson, A. R., Ngo, K., Clauson, C. L., Dong, Q., St. Croix, C., Sowa, G., Pola, E., Robbins, P. D., Kang, J., Niedernhofer, L. J., Wipf, P. and N.V. Vo.  (2013) Mitochondrial-derived reactive oxygen species (ROS) play a causal role in aging-related intervertebral disc degeneration.  J Orthop Res.  7:1150-7. PMC3668354 PubMed Link

Nasto, L. A., Wang, D., Robinson, A. R., Clauson, C. L., Ngo, K.,  Dong, Q., Roughley, P., Epperly, M., Huq, S. M., Pola, E., Sowa, G., Robbins, P. D., Kang, J., Niedernhofer, L. J., Vo, N.V. (2013) Genotoxic stress accelerates age-associated degenerative changes in intervertebral discs. Mech Ageing Dev., 134:35-42. PMC3558562 PubMed Link

Vo, N., Niedernhofer, L. J., Nasto, L. A., Jacobs, L., Robbins, P. D., Kang, J. and C. H. Evans (2013) An overview of underlying causes and animal models for the study of age-related degenerative disorders of the spine and synovial joints. J Orthop Res. 2013 Jun; 31:831-7. PMC3628921. PubMed Link

2014

Tilstra, J. S., Gaddy, D. F., Dave, S. H., Niedernhofer, L. J., Plevy, S. E. and Robbins, P. D. (2014) Pharmacologic NF-kB inhibition causes antigen presenting cells to undergo ROS-dependent programmed cell death. Sci. Rep. 4:3631. DOI: 10.1038/srep03631. PMID: 24406986  PubMed Link

Flores, R., Zhou, L. and Robbins, P. D. (2014) Expression of IL-2 in ß cells by AAV8 gene transfer in pre-diabetic NOD mice prevents diabetes through activation of FoxP3 positive regulatory T cells.  Gene Ther. 21:715-22. PMID: 24849041  PubMed Link

Gao, S., McMillian, R. P., Jacas, J., Zhu, Q., Li, X., Kumar, G. K., Casals, N., Hegardt, F. G., Robbins, P. D., Lopashuk, G. D., Hulver, M. W. and Butler, A. A. (2014) Regulation of Substrate Oxidation in Muscle by Peptide Hormone Adropin. Diabetes 63:3242-52. PMID: 24848071  PubMed Link

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2015

Proto, J.D., Tang, Y., Lu, A., Chen, W. C. W., Stahl, E., Poddar, M., Beckman, S. A., Robbins, P. D., Niedernhofer, L. J., K. Imbrogno, K., Hannigan, T., Mars, W. M., Wang, B. and Huard, J.  (2015)  NF-B inhibition reveals a novel role for HGF during skeletal muscle repair.  Cell Death & Dis. 6:e1730. DOI: 10.1038/cddis.2015.66.  PMID: 25906153  PubMed Link

Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A., Ding, H., Giorgadze, N., Palmer, A.K., Ikeno, Y., Borden, G., Lenburg, M., O’Hara, S. P., LaRusso, N. F., Miller, J. D., Roos, C. M., LeBrasseur, N. K., Wren, J. D., Farr, J. N., Khosla, S., Stout, M. B., McGowan, S. J., Fuhrmann-Stroissnigg, H., Gurkar, A. U., Zhao, J., Colangelo, D., Dorronsoro, A., Navarro, D.C., Sano, T., Robbins, P. D., Niedernhofer, L. J. and Kirkland, J.L.  (2015) Achilles’ heel of senescent cells: From transcriptome to senolytic drugs. Aging Cell DOI: 10.1111/acel.12344.  PMID: 25754370  PubMed Link

Reay, D. P., Bastacky, S. I., Wack, K. E., Stolz, D. B., Robbins, P. D. and Clemens, P. R.  (2015) D-amino acid substitution of peptide-mediated NF-kB suppression in mdx mice preserves therapeutic benefit in skeletal muscle, but causes kidney toxicity.  Mol. Med. DOI: 10.2119/molmed.2013.00141.  PMID: 26018805  PubMed Link

Zhang, Q., Ferrari, R., Beezhold, K., Stearns-Reider, K., D’Amore, A., Haschak, M., Stolz, D., Robbins, P. D., Barchowsky, A., and Ambrosio, F.  (2015) Chronic exposure to arsenic in drinking water promotes NF-B driven myofibroblasts dysfunction and matrix remodeling to impair muscle stem cell function.  Stem Cells doi: 10.1002/stem.2232.

2016

Zhao J, Fuhrmann-Stroissnigg H, Gurkar AU, Flores RR, Dorronsoro A, Stolz DB, St Croix CM, Niedernhofer LJ, Robbins PD., Quantitative Analysis of Cellular Senescence in Culture and In Vivo., Curr Protoc Cytom. 2017 Jan 5;79:9.51.1-9.51.25. DOI: 10.1002/cpcy.16, PMID: 28055114

Burd CE, Gill MS, Niedernhofer LJ, Robbins PD, Austad SN, Barzilai N, Kirkland JL, J Gerontol, Barriers to the Preclinical Development of Therapeutics that Target Aging Mechanisms.  A Biol Sci Med Sci. 2016 Nov;71(11):1388-1394. Epub 2016 Aug 16, PMID: 27535964 PMCID: PMC5055650 DOI: 10.1093/gerona/glw112

Montenegro-Burke JR, Phommavongsay T, Aisporna AE, Huan T, Rinehart D, Forsberg E, Poole FL, Thorgersen MP, Adams MW1, Krantz G2, Fields MW2, Northen TR, Robbins PD, Niedernhofer LJ, Lairson L, Benton HP, Siuzdak G.,  Smartphone Analytics: Mobilizing the Lab into the Cloud for Omic-Scale Analyses.  Anal Chem. 2016 Oct 4;88 (19):9753-9758. Epub 2016 Sep 15, PMID: 27560777 PMCID: PMC5054939 [Available on 2017-08-25] DOI: 10.1021/acs.analchem.6b02676

Takayama, K, Kawakami, Y, Lavasani, M, Mu, X, Cummins, JH, Yurube, T, Kuroda, R, Kurosaka, M, Fu, FH, Robbins, PD, Niedernhofer, LJ, Huard, J., mTOR signaling plays a critical role in the defects observed in muscle-derived stem/progenitor cells isolated from a murine model of accelerated aging., J Orthop Res. 2016 Aug 30. DOI: 10.1002/jor.23409. [Epub ahead of print], PMID: 27572850

Zhu Y., Tchkonia T., Fuhrmann-Stroissnigg, H., Dai, H.M., Ling, Y.Y., Stout, M.B., Pirtskhalava, T., Giorgadze, N., Johnson, K.O., Giles, C.B., Wren, J.D., Niedernhofer, L.J., Robbins, P.D., Kirkland, J.L. (2016) Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell. 15:428-35. PubMed Link

Zhang, C., Ferrari, R., Beezhold, K., Stearns-Reider, K., D'Amore, A., Haschak, M., Stolz, D., Robbins, P.D., Barchowsky, A., and Ambrosio, F. Arsenic Promotes NF-Κb-Mediated Fibroblast Dysfunction and Matrix Remodeling to Impair Muscle Stem Cell Function. Stem Cells. 2016 Mar; 34(3):732-42. DOI: 10.1002/stem.2232. Epub 2016 Jan 8.  PubMed Link

2017

Huerta Guevara, A. P., McGowan, S. J., Sano, T., Mulder, N. L., Jurdzinski, A., Flores, R. R., van Dijk, T Bloks, V. W., Eggen, B. J. L., Kazantzis, M., Boddeke, E. W.G.M. Hoeijmakers, J. H. J., Groen, A. K., Jonker, J. W., Robbins, P. D., Laura J. Niedernhofer, L. J. and Kruit, J. K.  Endogenous DNA damage promotes loss of pancreatic beta cell function and diabetes.  In preparation

Yousefzadeh, M. J., Schafer, M. J., Baker, D. J., Ladiges, W. C., Quarles, E., Robbins, P. D., LeBrasseur, N. K., and Niedernhofer, L. J. Serum MCP-1 as a biomarker of biological aging.  Aging Cell, under review

Flores, R. R., Corbo, L., Kim, E., van Meter, M., De Padilla, C. S. M., Zhao, J., Colangelo, D., Yousefzedeh, M., Vo, N., Evans, C. H., Gambotto, A., Niedernhofer, L. J., and Robbins, P. D.  Adenoviral gene transfer of IL-23 delays the onset of Type 1 diabetes while inducing psoriatic arthritis-like symptoms in NOD mice.  Submitted

Garcia-Contreras, M., Shah, S. H., Robbins, P. D., Golberg, R. B., Mendez, A. J., and Ricordi, C.  Plasma-derived Exosome microRNAs as novel biomarkers in type 1 diabetes.  2017 Jul 20;7(1):5998. DOI: 10.1038/s41598-017-05787-y PubMed Link

Huerta Guevara, A. P., McGowan, S. J., Sano, T., Mulder, N. L., Jurdzinski, A., Flores, R. R., van Dijk, T Bloks, V. W., Eggen, B. J. L., Kazantzis, M., Boddeke, E. W.G.M. Hoeijmakers, J. H. J., Groen, A. K., Jonker, J. W.,  Robbins, P. D., Laura J. Niedernhofer, L. J. and Kruit, J. K.  Endogenous DNA damage promotes loss of pancreatic beta cell function and diabetes.  In preparation.  

Dorronsoro, A., Corbo, L., McGowan, S. J., Lavasani, M., Liu, A. Brooks, R., Garcia-Contreras, M., Baker, D. J., Stolz, D., Amelio, A., Boregowda, S. V. Santiago, F., Fallahi, M., Ricordi, Phinney, D. C., Huard, J., Niedernhofer, L. J. and Robbins P. D. Extension of lifespan in a progeriod mouse model of accelerated aging by mesenchymal stem cells is mediated by extracellular vesicles. In preparation.  

Gurkar, A. U., Gregg, S. Q., Cui, Y., Yu, Y., Li, X., Allani, S. K., Fallahi, M., Medellin, N. C., Kelley, E. E., Weissbach, H., Robbins, P. D., St. Croix, C. M., Wang, Y., Niedernhofer, L. J. and Gill, M. S. Suppression of the mitochondrial unfolded protein response by persistent DNA damage drives aging via DAF-16/FOXO3A burn-out.  Nature Communications, Under Revision

Ngo, K., Pohl, P., Adriana, L., Lee, J., Di, P., Roughley, P., Robbins, P. D., Niedernhofer, L. J., Sowa, G., Kang, J. D., Shapiro, S. S. and Vo, N. ADAMTS5 deficiency protects mice from chronic tobacco smoking-induced intervertebral disc degeneration, Spine (Phila Pa 1976). 2017 May 31. doi: 10.1097/BRS.0000000000002258. [Epub ahead of print] Pubmed Link

Han, Y., Tan, J., Hartman, R. A., Dong, Q., Li, H., Zhao, J., Sowa, G. A., Kang, J. D. Niedernhofer, L. J., Robbins, P. D. and Vo, N.  Attenuation of ATM signaling mitigates cellular senescence and matrix loss in models of DNA damage-induced intervertebral disc aging. Submitted

Zhao, J, Lu, A., Colangelo, D., Chao, Y., Yousefzadeh, M., Li, X., McGowan S. J., Corbo, L., Sano, T., Bukata, C., Nick, H., Pola, E., Vo, N., Huard, J., Niedernhofer, L. J. and Robbins, P. D.  ATM regulates cellular senescence, stem cell function and aging. Submitted

Robinson, A. R. Gregg, S. Q, Wang, J., McGowan, S., Li, X., Gurkar, A. U., Skoda, E. M., Frantz, M-C., Tilstra, J. S., Pope-Varsalona, H., Ling, Y. Y., Nasto, L. A., Fuhrmann-Stroissnigg, H., Feldman, C., Maniar, S., St. Croix, C., Trussoni, C. E., LaRusso, N. F., Vo,  N., Opresko, P., Robbins, P. D., Burd, C.,  Wipf, P., Wang, Y.,  and Niedernhofer, L. J. Mitochondrial-derived Oxidative DNA Damage Drives Cellular Senescence and Aging.  Mol. Cell, Submitted

Rozgaja, T., Yousefzadeh, M., Li, X., Bell-Temin, H., Johnson, C., Robinson, R. A. S., Wang, J., Cantu-Medellin, N., Czerwinska, J., Harris,  J., Fallahi-Sichani, M., Cifuentes-Pagano, E., Pagano, P. J., Ross, M., Tudek, B., Robbins, P. D., Wang, Y., St. Croix, C., Yates, N., Siuzak, G., Niedernhofer, L. J., and Kelley, E. E.  ROS increases with aging due to increased production and decreased quenching/buffering.  Aging Cell, Submitted

Medvedev, A., Moeser, M., Medvedeva, L., Martsen, E. Granick, A., Raines, L., Zeng, M., Makarov Jr., S., Fuhrmann-Stroissnigg, H., Robbins, P. D., Hartzog, G., and Makarov, S. S. Identifying non-canonical inhibitors of the mTOR pathway by transcription factor profiling.  Submitted.

Zhao, J., Doebelin, C., Nguyen, W., Wallace, C., Reay, D. P., McGowan, S., Corbo, L., Clemens, P. R., Mustata-Wilson, G., Watkins, S. C., Solt, L. A., Cameron, M. D., Niedernhofer, L. J., Kamenecka, T. M. and Robbins, P. D.  Development of Novel NEMO-Binding Domain mimetics for inhibiting IKK/NF-kB activation.  Nature Comm., under revision

Proto, J. D., Lu, A., Robbins, P. D., Niedernhofer, L. J. and Huard, J.  Inhibition of NF-kB improves the stress resistance and myogenic differentiation of MDSPCs isolated from naturally aged mice. PLoS One. 2017 Jun 22;12(6):e0179270. DOI: 10.1371/journal.pone.0179270. eCollection 2017 PubMed Link

Fuhrmann-Stroissnigg, H., Ling, Y.Y., Zhao, J., McGowan, S., Zhu, Y., Dorronsoro, A., Gregg, S., Stripay, J., Corbo, L., Tang, P., Ring, N., Giacca, M., Li X., Tchkonia, T., Kirkland, J. L., Niedernhofer, L. J., and Robbins, P. D.  HSP90 inhibitors as senolytics for delaying onset of age-related diseases. Nature Communication, under review

Zhao J, Fuhrmann-Stroissnigg H, Gurkar AU, Flores RR, Dorronsoro A, Stolz DB, St Croix CM, Niedernhofer LJ, Robbins PD., Quantitative Analysis of Cellular Senescence in Culture and In Vivo., Curr Protoc Cytom. 2017 Jan 5;79:9.51.1-9.51.25. DOI: 10.1002/cpcy.16, PMID: 28055114 PubMed Link

Robbins PD and Niedernhofer LJ, Advances in Therapeutic Approaches to Extend Healthspan: a perspective from the 2nd Scripps Symposium on the Biology of Aging, Aging Cell. 2017 Aug;16(4):610-614. DOI: 10.1111/acel.12620. Epub 2017 Jun 6, PubMed Link

Huan T, Forsberg EM, Rinehart D, Johnson CH, Ivanisevic J, Benton HP, Fang M, Aisporna A, Hilmers B, Poole FL, Thorgersen MP, Adams MWW, Krantz G, Fields MW, Robbins PD, Niedernhofer LJ, Ideker T, Majumder EL, Wall JD, Rattray NJW, Goodacre R, Lairson LL and Siuzdak G, Systems biology guided by XCMS Online metabolomics, Nat Methods. 2017 Apr 27;14(5):461-462. DOI: 10.1038/nmeth.4260 PubMed Link

Zhu Y, Doornebal EJ, Pirtskhalava T, Giorgadze N, Wentworth M, Fuhrmann-Stroissnigg H, Niedernhofer LJ, Robbins PD, Tchkonia T and Kirkland JL, New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463, Aging (Albany NY). 2017 Mar 8;9(3):955-963. DOI: 10.18632/aging.101202 PubMed Link

Schafer MJ, White TA, Iijima K, Haak AJ, Ligresti G, Atkinson EJ, Oberg AL, Birch J, Salmonowicz H, Zhu Y, Mazula DL, Brooks RW, Fuhrmann-Stroissnigg H, Pirtskhalava T, Prakash YS, Tchkonia T, Robbins PD,Aubry MC, Passos JF, Kirkland JL, Tschumperlin DJ, Kita H and LeBrasseur NK, Cellular senescence mediates fibrotic pulmonary disease,  Nat Commun. 2017 Feb 23;8:14532. DOI: 10.1038/ncomms14532 PubMed Link

Flores RR, Clauson CL, Cho J, Lee BC, McGowan SJ, Baker DJ, Niedernhofer LJ and Robbins PD, Expansion of myeloid-derived suppressor cells with aging in the bone marrow of mice through a NF-κB-dependent mechanism, Aging Cell. 2017 Jun;16(3):480-487. DOI: 10.1111/acel.12571. Epub 2017 Feb 23 PubMed Link

Takayama K, Kawakami Y, Lavasani M, Mu X, Cummins JH, Yurube T, Kuroda R, Kurosaka M, Fu FH, Robbins PD, Niedernhofer LJ, Huard J, mTOR signaling plays a critical role in the defects observed in muscle-derived stem/progenitor cells isolated from a murine model of accelerated aging,  J Orthop Res.2017 Jul;35(7):1375-1382. DOI: 10.1002/jor.23409. Epub 2016 Sep 22 PubMed Link