Kenan Distinguished Professor of Microbiology and Immunology; UNC-CH
Joint Appointment in Biochemistry and Biophysics
PhD – California Institute of Technology
HONORS & AWARDS
- Progress Award from the Photographic Society of America, 2020.
- Elected to the National Academy of Sciences, 2018.
- Glenn Award, 2007. This award was given for contributions in aging research. Partial laboratory support for two years.
- Grand Gold Medal of Comenius University, Slovak Republic, 2006. This award is the highest honor of Comenius University and was given for contributions to molecular biology.
- Elected to the American Academy of Arts and Sciences, 2005.
- Named Kenan Distinguished Professor, UNC-Chapel Hill, 2002.
- Herbert A. Sober Award: Associated Societies for Biochemistry and Molecular Biology, 2002. This award is given once every two years nationally for someone who has contributed to molecular biology and biochemistry in the area of technique development.
- Ellison Senior Scholar Award, 2001-2005. Award for research on aging and telomeres. Four years of support for the laboratory.
- Elected Fellow of the American Association for the Advancement of Science, 2001.
Biochemistry & Visualization of Protein-DNA Interactions
The research program of the Griffith laboratory centers around basic questions of DNA-protein interactions as they impinge on cancer, AIDS and several inherited genetic diseases. While our laboratory is best known for using high resolution electron microscopy to visualize proteins bound to DNA, many other technologies are utilized including tissue culture, production of recombinant proteins in insect cells, in vivo footprinting and ligation mediated PCR. In studies of p53, possibly the most central protein in the pathway that protects cells from malignant transformation, we are investigating the ability of p53 to recognize different lesions in DNA, in particular those generated by oxidative damage and errors in replication. Parallel studies are probing the ability of the mismatch repair proteins MSH2,3,6 to recognize a spectrum of lesions in DNA. These proteins, in particular MSH2, are known to be mutated in hereditary non-polyposis colon cancer. Similar DNA-protein studies involve the human proteins TRF1 and TRF2 which bind to the sequences at the ends of human chromosomes, termed telomeres. The proteins regulate the activity of the telomerase enzyme that helps maintain telomere length. Cancer cells are known to be able to bypass these normal regulatory processes; hence understanding how TRF1 and 2 function is critical to understanding this pathway to transformation. Other studies focus on the fundamental arrangement of DNA at the replication fork in bacterial, viral (Herpes Simplex) and human cells. Our study of HIV centers on its chromatin structure as the HIV genome exists integrated in the human genome. Finally genomic instability is a hallmark of many cancers and several human genetic diseases including myotonic dystrophy. Our studies of the mechanism that give rise to these instabilities may pinpoint stages in the cell cycle where cells are most likely to have these instabilities arise. Our research program is greatly enriched by collaborations with Departmental colleagues in the Lineberger Cancer Center including Michael Topal and Aziz Sancar, and with investigators at other Universities including Thomas Cech, Paul Modrich, Richard Kolodner, Titia deLange and others. Click here to read more detailed research.
- Nicholls, TJ., Nadalutti, CA., Motori, E., Sommerville, EW., Gorman, GS., Basu, S., Hoberg, E., Turnbull, DM., Chinnery, PF., Larsson, NG., Falkenberg, M., Taylor, RW., Griffith, JD., and Gustafsson, CM. (2018) Topoisomerase 3a is Required for Decatenation and Segregation of Human mtDNA. Mol. Cell., 69:(1): 9-23.e6 PN+MID 29290614
- Ciesielski, GL., Nadalutti, CA., Olivera, MT., Jacobs, HT., Griffith, JD, and Kaguni, LS. (2018). Structural rearrangements in the mitochondrial genome of Drosophila melanogaster induced by elevated levels of the replicative DNA helicase. Nucleic Acids Res. Apr 6;46(6):3034-3046. doi: 10.1093/nar/gky094 PMID: 29432582
- McNamara, R., Costantini, L., Meyers, Schoust, B., Maness, N., Griffith, JD., Damania, B., MacLean, A., and Dittmer, D. (2018) Nef secretion into Extracellular Vesicles or exosomes is conserved across human and simian immunodeficiency viruses. MBio. Feb 6;9(1). pii: e02344-17. doi: 10.1128/mBio.02344-17 PMID: 29437924
- Amunugama, R,, Willcox, S., Wu, RA., Abdullah, UB., El-Sagheer, AH., Brown, T., McHugh, PJ., Griffith, JD., and Walter JC. (2018). Replication Fork Reversal During DNA Interstrand Crosslink Repair Requires CMG Unloading. Cell Reports. Jun 19;23(12) doi: 10.1016j.celrep. 2018.05.0613419-3428. PMID 29924986
- Kar, A., Jones, N., Arat, N-O., Fishel, R., and Griffith, JD. (2018). Long repeating (TTAGGG)n single stranded DNA self-condenses into compact beaded filaments stabilized by G-quadruplex formation. J. Biol. Chem. 2018 Jun 15;293(24):9473-9485. doi: 10.1074/jbc.RA118.002158. Epub 2018 Apr 19. PMID: 29674319
- Zhu, C., Beck, M.C., Griffith, J.D., Deshmukh, M., and Dokholyan, N.V. (2018). Large SOD1 aggregates, unlike trimeric SOD1, do not impact cell viability in a model of amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci.USA. Proc Natl Acad Sci U S A. 2018 May 1;115(18):4661-4665. doi: 10.1073/pnas.1800187115. Epub 2018 Apr 16.PMID: 29666246
- McNamara RP, Caro-Vegas CP, Costantini LM, Landis JT, Griffith JD, Damania BA, Dittmer DP. (2018). Large-scale, cross-flow based isolation of highly pure and endocytosis-competent extracellular vesicles. J Extracell Vesicles. 2018 Nov 30;7(1):1541396. doi: 10.1080/20013078.2018.1541396. eCollection PMID: 30533204
- Tomáška L, Nosek J, Sepšiová R, Cervenák F, Juríková K, Procházková K, Nebohácová M, Willcox S, Griffith JD. (2019). Commentary: Single-stranded telomere-binding proteins employs a dual rheostat for binding affinity and specificity that drives function. Front Genet. 2019 Jan 15;9:742. doi: 10.3389/fgene.2018.00742. eCollection 2018.
- McNamara RP, Chugh PE, Bailey A, Costantini LM, Ma Z, Bigi R, Cheves A, Eason AB, Landis JT, Host KM, Xiong J, Griffith JD, Damania B, Dittmer DP. (2019) Extracellular vesicles from Kaposi Sarcoma-associated herpesvireus lymphoma induce long-term endothelial cell reprogramming. PLoS Pathog. Feb 4;15(2):e1007536. doi: 10.1371/journal.ppat.1007536. eCollection 2019 Feb.
- Tomaska L, Nosek J, Kar A, Willcox S, Griffith JD. (2019). A new view of the T-loop Junction: Implications for Self-Primed Telomere Extension, Expansion of Disease-Related Nucleotide Repeat Blocks and Telomere Evolution. Front Genet. 2019 Aug 14;10:792. doi: 10.3389/fgene.2019.00792. eCollection 2019.PMID: 31475042