Kip E. Guja
B.S. Johns Hopkins, 2006
M.S. Johns Hopkins, 2007
Ph.D. Stony Brook University, 2015
8th Year MSTP
4th Year Medical Student
Advisor: Miguel Garcia-Diaz, PhD
Department: Pharmacological Sciences, Stony Brook University
Graduate Program: Biochemstry & Structural Biology
Title: Structural insights into mitochondrial gene expression and disease
Abstract:
Mitochondria are responsible for the vast majority of cellular energy production through oxidative phosphorylation. The efficiency and regulation of oxidative metabolism is critical to sustain different physiological processes. Mitochondrial deficiencies that affect oxidative metabolism are linked to aging, neurodegeneration, and a variety of genetic mitochondrial diseases. Mitochondrial function is strictly dependent on the expression of the mitochondrial genome, and mitochondrial gene transcription is a key link in this process. I am utilizing a combination of structural (mainly X-ray crystallography), biochemical, and genetic approaches to understand the molecular details of mitochondrial gene expression, its control by nuclear hormone receptors, and the deleterious effects of pathogenic mitochondrial DNA mutations on these processes. This work has important implications for a number of human diseases and may lead to new potential avenues for therapeutics.
Awards:
Julian David Baumert Ph.D. Thesis Award – Brookhaven National Laboratory
Publications:
(MSTP-supported publications indicated with an *)
Guja KE, Schildbach JF. (2015). Completing the specificity swap: Single-stranded DNA recognition by F and R100 TraI relaxase domains. Plasmid. [Epub 2015 Apr 1]. PMID: 25841886
Burak MJ, Guja KE, Hambardjieva E, Derkunt B, Garcia-Diaz M. 2016. "A novel fidelity mechanism in DNA polymerase lambda promotes error-free bypass of 8-oxo-dG." The EMBO Journal. DOI 10.15252/embj.201694332
Georghiou G, Aleem S. Kleiner RE, Guja KE, Craddock BP, Lyczek A, Chan AI, Kleiner R, Garcia-Diaz M, Liu DR, Miller WT, Seeliger MA. 2016. “Structural and biochemical basis for inhibition of breast cancer cell migration and drug-resistance mutations by Src-specific macrocyclic inhibitors.” Cell Chemical Biology. In press (accepted 7/14/16)
Guha M, Srinivasan S, Guja KE, Mejia E, Garcia-Diaz M, Johnson FB, Ruthel G, Kaufman BA, Rappaport EF, Glineburg MR, Fang JK, Szanto AK, Nakagawa H, Basha J, Kundu T, Avadhani NG. 2016. “Mitochondrial Defects Induce Telomere Attrition and Altered Nuclear Gene Expression by Regulating Histone Acetylation.” Cell Research. Submitted, currently in peer review.
*Yang M, Lu R, Guja KE, Wipperman MF, St. Clair JR, Bonds AC, Garcia-Diaz M, Sampson NS. (2015). Unraveling Cholesterol Catabolism in Mycobacterium tuberculosis: ChsE4-ChsE5 α2β2 Acyl-CoA Dehydrogenase Initiates β-Oxidation of 3-Oxo-cholest-4-en-26-oyl CoA. ACS Infectious Diseases. 1(2):110–125. PMID: N/A. DOI: 10.1021/id500033m
*Guja KE, Venkataraman K, Yakubovskaya E, Shi H, Mejia E, Hambardjieva E, Karzai AW, Garcia-Diaz M. (2013). Structural basis for S-adenosylmethionine binding and methyltransferase activity by mitochondrial transcription factor B1.Nucleic Acids Research. 41(16):7947-59. PMID: 23804760.
*Yang M, Guja KE, Thomas ST, Garcia-Diaz M, Sampson NS. (2014). A Distinct MaoC-like Enoyl-CoA Hydratase Architecture Mediates Cholesterol Catabolism in Mycobacterium tuberculosis. ACS Chemical Biology. PMID: 25203216.
*Venkataraman K, Guja KE, Garcia-Diaz M, Karzai AW. (2014). Nonstop mRNA Decay: a Special Attribute of Trans-Translation Mediated Ribosome Rescue.Frontiers in Microbiology. PMID: 24653719.
*Yakubovskaya E1, Guja KE, Eng ET, Choi WS, Mejia E, Beglov D, Lukin M, Kozakov D, Garcia-Diaz M. (2014). Organization of the human mitochondrial transcription initiation complex. Nucleic Acids Research. PMID: 24413562. 1Equal contribution.
*Jacewicz A, Trzemecka A, Guja KE, Plochocka D, Yakubovskaya E, Bebenek A, Garcia-Diaz M. A remote palm domain residue of RB69 DNA polymerase is critical for enzyme activity and influences the conformation of the active site. PLoS One. PMID: 24116139.
*Guja KE, Garcia-Diaz M. (2012). Hitting the brakes: Termination of mitochondrial transcription. Biochimica et Biophysica Acta. 1819(9-10):939-947. PMID:22137970.
*Yakubovskaya E1, Guja KE, Mejia E1 , Castano S, Hambardjieva E, Choi WS, and Miguel Garcia-Diaz. (2012). Structure of the Essential MTERF4:NSUN4 Protein Complex Reveals How an MTERF Protein Collaborates to Facilitate rRNA Modification. Structure. 20(11):1940-7. PMID 23022348. Equal contribution.
Anderson, B. J., Larkin, C., Guja, K., and Schildbach, J. F. (2008). Using fluorophore-labeled oligonucleotides to measure affinities of protein-DNA interactions. Methods in Enzymology. 450:253-272. PMID: 19152864.
Hekman, K., Guja, K., Larkin, C., and Schildbach, J. F. (2008). An intrastrand three-DNA-base interaction is a key specificity determinant of F transfer initiation and of F TraI relaxase DNA recognition and cleavage. Nucleic Acids Research. 36(14):4565-4572. PMID: 18611948.
