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Mitochondrial respiration, oxidative damage, and aging





Joan E. McEwen, Ph.D.



Joan E. McEwen, Ph.D

Associate Professor

Department of Geriatrics


Research interests:



















Name                                       Joan E. McEwen




            1974                             B.A.     Tufts University, Biology, summa cum                                                    laude

            1980                             Ph.D.   Albert Einstein College of Medicine,                                                       Molecular Biology


Professional Experience


                                                1974-1980                     Predoctoral Fellow, Albert Einstein College of                                         Medicine

                                    Preceptor: Dr. Philip M. Silverman

                                                1980-1984                     Postdoctoral Fellow, University of Colorado

                                                                                    Preceptor: Dr. Robert O. Poyton

                                                1984-1993                     Assistant Professor, Department of                                                        Microbiology and Molecular Genetics, UCLA

                                                1993-1995                     Associate Research Scientist, Dept. of                                                   Molecular Genetics, Beckman Research                                                             Institute, City of Hope Medical Center

                                                1995-present                 Associate Professor, Dept. of Geriatrics,                                                            University of Arkansas for Medical Sciences;                                        and Research Health Scientist, GRECC, J.L.                                                 McClellan VA Hospital



Honors and Awards


            1974                             Phi Beta Kappa

                                                1975-1980                     NIH Fellowship, Pre-doctoral Training Grant

            1980-1981                     Damon Runyan Postdoctoral Fellowship

            1981-1984                     NIH Postdoctoral Fellowship




            American Society for Microbiology

            American Association for the Advancement of Science

            Genetics Society of America



Research Interests        Role of mitochondrial respiration and oxidative damage in organismal longevity.  Nuclear-mitochondrial interactions in the development and function of mitochondria in S. cerevisiae and in the human pathogenic fungus H. capsulatum.

Scholarly Service


            1989                             Ad hoc member of Microbiology and Virology                                         study section for American Cancer Society


                                    1984-1993                     Ad hoc reviewer of grant proposals to Jonsson                                        Cancer Center of UCLA


1994                                                          Ad hoc member of Physiological Chemistry                                            study section, NIH


2000                             panelist, microbial genetics review panel, NSF


                                                1984-present                 Ad hoc reviewer of manuscripts for Science, J.                                                   Bacteriol., Nucl. Acids   Research, Mol.                                                              Microbiol.



Selected University or Departmental Service


            1986-1990                     Five Faculty search committees for the Dept. of                                      Microbiology and Molecular Genetics at UCLA


            1986-1991                     Committee for design of new Microbiology and                                       Molecular Genetics building at UCLA


                                                1991-1993                     Committee for design of renovated teaching lab                                       space for the Dept. of Microbiology and                                                             Molecular Genetics at UCLA


            1989-1992                     Graduate Admissions Committee for the                                                 Molecular Biology Institute at UCLA


                                    1988-1993                     Chairman of Honors program for majors in the                                        Department of Microbiology and Molecular                                             Genetics at UCLA


1984-1995                     Mentor for four Ph.D. students who conducted their dissertation research in my laboratory at UCLA.  Student names:  Jeffrey D. Ohmen, Maria L. Valencik, Kathleen M. Calder, and Glenn M. Manthey.


1994-1995                                          Graduate Admissions Committee for the Ph.D. program at Beckman Research Institute, City of                                              Hope Medical Center


1999-2002                                      Vice chairman of the Animal Care and Use Committee of Central Arkansas Veterans Healthcare System.


2002-present              Chairman of the Animal Care and Use Committee of Central Arkansas Veterans Healthcare System


1999-2002                   Member of Research and Development committee of Central Arkansas Veterans Healthcare system


Selected community service


            1989, 1990                    Faculty mentor in minority undergraduate                                                summer research program at UCLA


1998-2001                   Membership chairman and member of board of Directors of Diamond Edge Figure Skating Club of Little Rock, AR (a 501C3 tax exempt organization with charitable activities)


2004-present              Member of board of Directors of Diamond Edge Figure Skating Club of Little Rock, AR (a 501C3 tax exempt organization with charitable activities)


Selected Teaching Experience


Microbiology and Molecular Genetics 101, UCLA

This is an undergraduate upper division course on "Fundamentals of Microbiology".  This course, which consists of both lecture and laboratory, is required for majors of two departments - Dept. of Microbiology and Molecular Genetics and Dept. of Biochemistry - and is an important elective course for Biology majors.

Times taught:                1986, Spring

1987, Spring

1988, Spring

                                                            1989, Spring

                                                            1989, Fall

                                                            1991, Spring

                                                            1991, Fall

                                                            1992, Fall


Microbiology and Molecular Genetics 195H, UCLA

This is an upper division seminar/discussion course for students in the Honors program.

Times taught:                1987, Spring

                                                            1989, Spring

1990, Spring

1991, Spring

                                                            1992, Spring

                                                            1993, Spring


Graduate seminar courses at UCLA, 1984-1995, on a variety of topics, including "Mitochondrial gene expression"; "Regulation of prokaryotic metabolism"; "Regulation of cytochrome genes in bacteria and yeast"; "Mechanisms of RNA splicing"; "Translational control of gene expression"; "Protein targeting in prokaryotes and eukaryotes"; "Prokaryotic development and cell-cell interactions".


Mentoring of undergraduate students in independent research, 1984-1995.  I had from 1-3 undergraduate students per quarter working in my laboratory on independent research projects, for which they received course credit.


            Lectures on protein synthesis to graduate students at Beckman Research Institute at City of Hope             Medical Center

                                                            Times taught:                1994



            Lectures (4) on yeast genetics to graduate students in MBIM 5123 class, Dept. of Microbiology and Immunology, UAMS

                                                            Times taught:                1996




            Lectures (6) on bacterial and yeast genetics to graduate students in MBIM 5023 class (Principles of Microbiology, Dept. of Microbiology and Immunology, UAMS

                                                            Times taught:





Lectures (3) on yeast physiology and metabolism to graduate students in MBIM 5023 class (Principles of Microbiology)

                                                Times taught:





Lectures (2) on fungal pathogens in Medical Microbiology for Medical Students class

                                                Times taught:             1999







Lectures (2) on prokaryotic protein synthesis to graduate students in Physiology/MBIM Gene expression course

                                                Times taught:             2001





Published articles (peer reviewed)


l.          McEwen, J. and P. Silverman.  l980.  Chromosomal mutations of Escherichia coli that alter expression of conjugative plasmid functions.  Proc. Natl. Acad. Sci. U.S.A.  77:513-517.


2.         Silverman, P., K. Nat, J. McEwen, and R. Birchman.  l980.  Selection of Escherichia coli K12 chromosomal mutants that prevent expression of F-plasmid functions.  J. Bacteriol.  143:1519-1523.


3.         McEwen, J., and P. Silverman.  l980.  Genetic analysis of Escherichia coli K-12 chromosomal mutants defective in expression of F-plasmid functions: Identification of genes cpxA and cpxB.  J. Bacteriol.  l44:60-67.


4.         McEwen, J., and P. Silverman.  l980.  Mutations in genes cpxA and cpxB of Escherichia coli K-12 cause a defect in isoleucine and valine syntheses.  J. Bacteriol.  l44:68-73.


5.         Sutton, A., T. Newman, J. McEwen, P. Silverman and M. Freundlich.  l982.  Mutations in genes cpxA and cpxB of Escherichia coli K12 cause a defect in Acetohydroxyacid Synthase I function in vivo.  J. Bacteriol.  l5l:976-982.


6.         McEwen, J. and P. Silverman.  l982.  Mutations in genes cpxA and cpxB alter the protein composition of Escherichia coli inner and outer membranes.  J. Bacteriol.  l5l:l553-l559.


7.         McEwen, J., L. Sambucetti, and P. Silverman.  l983.  Synthesis of outer membrane proteins in cpxA cpxB mutants of Escherichia coli K12.  J. Bacteriol.  l54:375-382.


8.         Cumsky, M., J. McEwen, C. Ko, and R. Poyton.  l983.  Nuclear genes for mitochondrial proteins:  Identification and isolation of a structural gene for subunit V of Yeast cytochrome c oxidase.  J. Biol. Chem.  258:13418-13421.


9.         McKee, E., J. McEwen, and R. Poyton.  1984.  Mitochondrial gene expression in Saccharomyces cerevisiae.  II.  Fidelity of translation in isolated mitochondria from wild-type and respiratory-deficient mutant cells.  J. Biol. Chem.  259:9332-9338.


10.        McEwen, J., M. Cumsky, C. Ko, S. Power and R. Poyton.  l984.  Mitochondrial membrane biogenesis:  Characterization and use of Pet mutants to clone the nuclear gene coding for subunit V of Yeast cytochrome c oxidase.  J. Cell. Bioch.  24:229-242.


11.        McEwen, J., V. Cameron and R. Poyton.  l985.  A rapid method for the isolation and screening of cytochrome c oxidase-deficient mutants of Saccharomyces cerevisiae.  J. Bacteriol.  161:831-835.


12.        McEwen, J., C. Ko, B. Kloeckener-Gruissem and R. O. Poyton.  1986.  Nuclear functions required for cytochrome c oxidase biogenesis in Saccharomyces cerevisiae.  Characterization of mutants in 34 complementation groups.  J. Biol. Chem.  261:11872-11879.
13.        Kloeckener-Gruissem, B., J. McEwen and R. Poyton.  1987.  Nuclear functions required for cytochrome c oxidase biogenesis in Saccharomyces cerevisiae.  Multiple trans-acting nuclear genes exert specific effects on expression of each of the cytochrome c oxidase subunits encoded on mitochondrial DNA.  Current Genetics  12: 311-322.


14.        Kloeckener-Gruissem, B., J. McEwen and R. Poyton.  1988.  Identification of a third nuclear protein-coding gene required specifically for expression of the mitochondrial COX3 gene in S. cerevisiae.  J. Bacteriol. 170: 1399-1402.


15.        Ohmen, J., B. Kloeckener-Gruissem, and J. McEwen.  1988.  Molecular cloning and nucleotide sequence of the nuclear PET122 gene that is required for expression of the mitochondrial COX3 gene in S. cerevisiae.  Nucleic Acids Res. 16: 10783-10802.


16.        Valencik, M.L, B. Kloeckener-Gruissem, R.O. Poyton, and J.E. McEwen.  1989.  Disruption of the yeast nuclear PET54 gene blocks excision of mitochondrial intron aI5ß from pre-mRNA for cytochrome c oxidase subunit I.  EMBO J. 8: 3899-3904.


17.        Calder, K.M., and J.E. McEwen.  1990.  Nucleotide sequence of the gene encoding cytochrome c oxidase subunit VII from Saccharomyces cerevisiae.  Nucleic Acids Res. 18: 1632-1632.


18.        Ohmen, J.D., K.A. Burke, and J.E. McEwen.  1990.  Divergent overlapping transcripts at the PET122 locus in Saccharomyces cerevisiae. Mol. Cell. Biol. 10: 3027-3035.


19.        Valencik, M.L., and J.E. McEwen.  1991.  Genetic evidence that different functional domains of the PET54 gene product facilitate expression of the mitochondrial genes COX1 and COX3 in S. cerevisiae.  Mol. Cell. Biol. 11: 2399-2405.


20.        Calder, K.M., and J.E. McEwen.  1991.  Deletion of the COX7 gene in Saccharomyces cerevisiae reveals a role for cytochrome c oxidase subunit VII in assembly of remaining subunits.  Mol. Micro. 5: 1769-1777.


21.        Burke, K.A., and J.E. McEwen.  1991.  Characterization of mRNAs and coding potential of the PET54 gene from Saccharomyces cerevisiae.  Biochem. International, 25: 339-348.


22.        McEwen, J.E., Hong, K.H., Preciado, G.T., and Park, S.  1993.  Sequence and chromosomal localization of two PET genes required for cytochrome c oxidase assembly in Saccharomyces cerevisiae.  Curr. Genet. 23:  9-14.


23.        Marathe, S., and McEwen, J.E.  1995.  Vectors with the GUS gene as a reporter for identifying and quantitating promoter regions in Saccharomyces cerevisiae.  Gene 154: 105-107.


24.        Manthey, G.M., and McEwen, J.E.  1995.  The product of the nuclear gene PET309 is required for translation of mature mRNA and stability or production of intron-containing RNAs derived from the mitochondrial COX1 locus in Saccharomyces cerevisiae.  EMBO J 14: 4031-4043.


25.        Poyton, R.O., and McEwen, J.E.  1996.  Cross-talk between nuclear and mitochondrial genomes.  Ann. Rev. Biochem. 65: 563-607. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8811190&query_hl=1


26.        Johnson, C.H., and McEwen, J.E.  1997.  Mitochondrial protein synthesis is not required for efficient excision of intron aI5b from COX1 pre-mRNA in Saccharomyces cerevisiae.  Mol. Gen. Genet. 256: 88-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9341683&query_hl=1


27.        Manthey, G.M., Przybyla-Zawislak, B.D., and McEwen, J.E.  1998.  The Saccharomyces cerevisiae  Pet309 protein is embedded in the mitochondrial inner membrane.  Eur. J. Bioch. 255: 156-161. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9692914&query_hl=1


28.               Johnson, C.H., and McEwen, J.E.  1999.  Isolation of a Histoplasma capsulatum cDNA that complements a mitochondrial NAD(+)-isocitrate dehydrogenase subunit I-deficient mutant of Saccharomyces cerevisiae. Yeast 15: 799-804. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10398348&query_hl=1


29.Marathe, S.V., and McEwen, J.E. 1999.  Expression of the divergent transcription unit containing the yeast PET122 and OXA1 genes. Bioch. And Mol. Biol. Int.  47: 971-977. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10410243&query_hl=1


30.               Johnson, C.H., Klotz, M.G., York, J.L., Kruft, V. and McEwen, J.E. 2002. Redundancy, phylogeny and differential expression of Histoplasma capsulatum catalases.  Microbiology148: 1129-1142. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11932457&query_hl=1


31.               Ranganathan, G., Phan, D., Pokrovskaya, I.D., McEwen, J.E., Li, C. and Kern, P.A. 2002. The translational regulation of Liproprotein lipase by Epinephrine involves an RNA binding complex Including the Catalytic Subunit of Protein Kinase A.  J. Biol. Chem. 277: 43281-43287. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12218046&query_hl=1


32.               Johnson, C.H., Prigge, J.T., Warren, A.D. and McEwen, J.E. 2003. Characterization of an alternative oxidase activity of  Histoplasma capsulatum.  Yeast 20: 381-388. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12673621&query_hl=1


33.               Missal, T.A., Lodge, J.K., and McEwen, J.E.  2004.  Mechanisms of resistance to oxidative and notrosative stress: Implications for fungal survival in mammalian hosts.  Eukaryotic Cell 3:  835-846. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15302816&query_hl=1


34.               McEwen, J.E., Zimniak, P., Mehta, J.L., and Reis, R.J. 2005.  Molecular pathology of aging and its implications for senescent coronary atherosclerosis.  Current Opinion in Cardiology 20: 399-405. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16093759&query_hl=1