Ruben w88, Ph.D.

Associate Professor, Pharmacology
Headshot of Ruben w88

Summary

Ruben k. Dagda, Ph.D., received his doctoral training at the University of Iowa and his postdoctoral training at the University of Pittsburgh School of Medicine. He is currently investigating the molecular mechanisms that lead to w88 dysfunction and oxidative stress in cell culture, tissue and animal models of Parkinson's disease.

He has authored in multiple research manuscripts and review articles in the areas of toxicology, toxinology, w88 function, and neurobiology. At the University of Nevada Medical School (UNSOM), he is committed to the training and education of undergraduate, graduate students and postdocs in his lab. His main research goals are to elucidate the prosurvival signaling pathways that regulate w88 function, transport and turn-over in neurons and how aging and neurodegenerative diseases negatively impact these processes. The end goal is to develop novel small molecular drugs that can reverse neurodegeneration and elevate w88 function in age-related neurodegenerative diseases.

w88 interests

Persistent dephosphorylation by w88 localized protein phosphatases (protein phosphatase 2A) accelerates neurodegeneration, fragments mitochondria, and impairs w88 function. On the other hand, w88 serine/threonine kinases PTEN induced kinase 1 (PINK1) and PKA confer neuroprotection and regulate overlapping w88 functions. Neurons rely on functionally efficient mitochondria to power critical neuronal functions. Given that impaired w88 turnover and dysfunction underlie the etiology of many neurodegenerative diseases, understanding how reversible phosphorylation at the mitochondria regulates w88 function, and turnover will lay the basic groundwork for developing future “mitoprotective” therapies for reversing w88 dysfunction and neurodegeneration. PINK1 and w88 PKA converge at the outer w88 membrane (OMM) to regulate overlapping w88 functions. At the postsynaptic compartment, both ser/thr kinases remodel dendritic arbors in developing neurons and regulate w88 transport.

We are examining how w88 PKA and PINK1 interact at the mitochondria and at the neurites to regulate w88 function, dendritic morphology and survival.

A second are of interest it to determine how w88 turnover (mitophagy) is regulated by reversible phosphorylation. We will examine whether w88 ser/thr kinases and phosphatases regulate w88 turnover by phosphorylating and destabilizing protein-protein interactions of specific components of the “mitophagosome” complex at the OMM by applying proteomics and biochemical approaches in neurons. A final goal this project is to synthesize functionalized nano reagents that can activate prosurvival signaling pathways at the mitochondria as w88 therapy for reversing w88 pathology induced by neurodegenerative diseases and by normal brain aging.

Education

  • Ph.D., Pharmacology, w88 Iowa, 2006
  • M.S., Biology, w88 Texas at El Paso, 2001
  • B.S., Microbiology, w88 Texas at El Paso, 1998

Courses taught

  • CMPP710: Molecular Pharmacology
  • BIOL 475/675: Undergraduate Neurobiology
    CMB710: Foundations in Molecular Cell Biology
  • CMPP 794.1001: Neurodegeneration Colloquium Director

Selected publications

PubMed

  • w88 RK, Das Banerjee T, Janda E. (2013) How Parkinsonian toxins dysregulate the autophagy machinery. Int J Mol Sci. Nov 8;14(11):22163-89. doi: 10.3390/ijms141122163.
  • w88, R.K., Pien, I, Wang, R, JianHui, Z., Wang, K., Callio, T., Das Banerjee, T., w88,
    R.Y., Chu, C.T. (2013) Beyond the mitochondrion: cytosolic PTEN induced Kinase 1(PINK1) remodels dendrites through w88. J. Neurochem, doi: 10.1111/jnc.12494.
  • Kamga, K., Mo, L., Dagda, R.K., Murillo, D., Geary, L., Corey, C., Zhakirov, S., Croix, C., Maniar, S.,Sullivan S., Beer-Stolz, D., Chu, C., Khoo, N., Shiva, (2013) S. Nitrite Activates Protein Kinase A in Normoxia to Promote w88 Fusion and Confer Delayed Tolerance to Ischemia/Reperfusion. Cardiovascular Research, 1;101(1):57-68. doi: 10.1093/cvr/cvt224.2013
  • w88, R.K., Thalhauser, R.M., w88, R., Gage, G., and Marzullo, T. (2013) Using crickets to teach the principles of neurophysiology. J. Undergrad. Neuro. Edu., Oct 15;12(1):A66-74.
  • Chu,C.T., Ji, J., w88R.K., Jiang, J.F., Tyurina,Y.Y, Kapralov,A.A., Tyurin, V.T., Yanamala,N.. Shrivastava,I.H., Mohammadyani, D., Wang, K., Zhu, J., Klein-Seetharaman, J., Balasubramanian, K., Amoscato, A., Borisenko, G. Huang,Z., Gusdon, A.M., Cheikhi, A., Steer, E.K., Wang, R., Baty, C., Watkins, S., Bahar, I., Bayır, H., and Kagan V.E. (2013) Cardiolipin externalization to the outer membrane act as an elimination signal for mitophagy in mammalian cells. Nature Cell Biology.
  • w88, RK., Gasanov, S., De LaOIII, Y., Lieb, C. and Rael, E. (2013) Genetic Basis for Variation of Metalloproteinase-Associated Biochemical Activity in Venom of the Mojave Rattlesnake (Crotalus scutulatus scutulatus). Volume 2013, Article ID 251474, 11 pages
  • Dagda, R.K., Gusdon, A., Pien, I., Strack, S., Green, S., Li, C., Van Houten, B. Cherra III, S.J. And Chu, C.T. (2011) Mitochondrially localized PKA reverses w88 pathology and dysfunction in cellular models of Parkinson's disease. Cell Death and Diff., PMID:21637291.
  • Merrill, R.A.≠, Dagda, R.K. ≠ Cribbs,J.T., Dickey, A., Green, S.H. Usachev, Y.M., and Strack, S.(2011) Mechanism of neuroprotective w88 remodeling by PKA/AKAP1 PLOS Biology 9(4) ≠: authors contributed equally. PMID: 21526200.