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 mitochondrial 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, mitochondrial 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 mitochondrial 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 mitochondrial function in age-related neurodegenerative diseases.
Persistent dephosphorylation by mitochondrial localized protein phosphatases (protein phosphatase 2A) accelerates neurodegeneration, fragments mitochondria, and impairs mitochondrial function. On the other hand, mitochondrial serine/threonine kinases PTEN induced kinase 1 (PINK1) and PKA confer neuroprotection and regulate overlapping mitochondrial functions. Neurons rely on functionally efficient mitochondria to power critical neuronal functions. Given that impaired mitochondrial turnover and dysfunction underlie the etiology of many neurodegenerative diseases, understanding how reversible phosphorylation at the mitochondria regulates mitochondrial function, and turnover will lay the basic groundwork for developing future “mitoprotective” therapies for reversing mitochondrial dysfunction and neurodegeneration. PINK1 and mitochondrial PKA converge at the outer mitochondrial membrane (OMM) to regulate overlapping mitochondrial functions. At the postsynaptic compartment, both ser/thr kinases remodel dendritic arbors in developing neurons and regulate mitochondrial transport.
We are examining how mitochondrial PKA and PINK1 interact at the mitochondria and at the neurites to regulate mitochondrial function, dendritic morphology and survival.
A second are of interest it to determine how mitochondrial turnover (mitophagy) is regulated by reversible phosphorylation. We will examine whether mitochondrial ser/thr kinases and phosphatases regulate mitochondrial 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 mitochondrial therapy for reversing mitochondrial pathology induced by neurodegenerative diseases and by normal brain aging.
- Ph.D., Pharmacology, University of Iowa, 2006
- M.S., Biology, University of Texas at El Paso, 2001
- B.S., Microbiology, University of Texas at El Paso, 1998
- CMPP710: Molecular Pharmacology
- BIOL 475/675: Undergraduate Neurobiology
CMB710: Foundations in Molecular Cell Biology
- CMPP 794.1001: Neurodegeneration Colloquium Director
- Dagda 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.
- Dagda, R.K., Pien, I, Wang, R, JianHui, Z., Wang, K., Callio, T., Das Banerjee, T., Dagda,
R.Y., Chu, C.T. (2013) Beyond the mitochondrion: cytosolic PTEN induced Kinase 1(PINK1) remodels dendrites through PKA. 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 Mitochondrial Fusion and Confer Delayed Tolerance to Ischemia/Reperfusion. Cardiovascular Research, 1;101(1):57-68. doi: 10.1093/cvr/cvt224.2013
- Dagda, R.K., Thalhauser, R.M., Dagda, 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., Dagda,R.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.
- Dagda, 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 mitochondrial 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 mitochondrial remodeling by PKA/AKAP1 PLOS Biology 9(4) ≠: authors contributed equally. PMID: 21526200.