Medical Science, Room MS4032D
Indianapolis, IN 46202
Bio
Dr. Millie M. Georgiadis received her Ph.D. in 1990 in Biochemistry from the University of California, Los Angeles, working with Dr. Douglas Rees, now at the California Institute of Technology. Her graduate work focused on structure-function studies of the nitrogen fixing enzyme complex nitrogenase and culminated in the determination of the novel crystal structure of the nitrogenase iron protein. Dr. Georgiadis pursued postdoctoral studies at Columbia University under the direction of Dr. Wayne Hendrickson, where she focused on the application of multiple wavelength anomalous dispersion (MAD) methods for phasing crystal structures. She determined a high resolution crystal structure of the N-terminal fragment of Moloney murine leukemia virus reverse transcriptase (MMLV RT) using mercury MAD phasing methods. Her structural and functional studies led to a steric mechanism to explain how a DNA polymerase like MMLV RT distinguishes dNTP from NTP substrates. As an Assistant Professor at Rutgers University, Dr. Georgiadis continued working on the structural basis of protein-nucleic acid interactions. Her laboratory determined crystal structures of MMLV RT bound to DNA, Ndt80, and Tap (NFX1) and developed a host-guest system for the crystallization and analysis of novel DNA sequences of interest. Dr. Georgiadis moved to Indiana University School of Medicine (IUSM) as an Associate Professor with tenure in 2002 and has since advanced to Full Professor. Her laboratory has expanded its interest in protein-nucleic acid and DNA-ligand interactions and, in several collaborative projects with colleagues at IUSM and IUPUI, has determined novel crystal structures of bleomycin bound to DNA, the catalytic domain of SETMAR, a chimeric fusion protein present only in anthropoid primates, the DNA-binding domain of SETMAR bound to its cognate TIR DNA sequence, and the C-terminal regulatory domain of GCN2, the eIF2 kinase that senses amino acid deprivation. Current cancer-related projects include genomic and structural studies of SETMAR to determine its role in normal and cancer cells and identification of small molecule modulators of the DNA repair protein, apurinic/apyrimidinic endonuclease 1 (APE1), for the treatment of cancer and chemo-induced peripheral neuropathy in collaboration with IUSM researchers. In a new synthetic biology project, the Georgiadis laboratory is pursuing structural characterization of artificial DNA and its interactions with DNA polymerases in collaboration with investigators from the Foundation for Applied Molecular Evolution.
Key Publications
Hoshika, S., Leal, N.A., Kim, M.J., Kim, M.S., Karalkar, N.B., Kim, J.G., Bates, A.M., Watkins, N.E., Jr., SantaLucia, H.A., Meyer, A.J., DasGupta, S., Piccirilli, J.A. Ellington, A.D. SantaLucia, J., Jr., Georgiadis, M.M., Benner, S.A. (2019) Hachimoji DNA and RNA: A genetic system with eight building blocks. Science 363, 884-887. PMCID: PMC6413494 DOI: 10.1126/science.aat0971
Ouaray, Z., Benner, S.A., Georgiadis, M.M., and Richards, N.G.J. (2020) Building better polymerases: Engineering the replication of expanded genetic alphabets. J Biol Chem 295, 17046-17059. PMID: 33453957 DOI: 10.1074/jbc.REV120.013745
Wilson, D.M., III, Deacon, A.M., Duncton, M.A.J., Pellicena, P., Georgiadis, M.M., Yeh, A.P., Arvai, A.S., Moiani, D., Tainer, J.A., and Das, D. (2020) Fragment- and structure-based drug discovery for developing therapeutic agents targeting the DNA Damage Response. Prog Biophys Mol Biol, S0079-6107(20)30111-5. PMID: 33115610 DOI: 10.1016/j.pbiomolbio.2020.10.005
Paavola, J.L., Battistin, U., Ogata, C.M., and Georgiadis, M.M. (2021) Crystal structures of a dodecameric multicopper oxidase from Marinithermus hydrothermalis. Acta Cryst D 77, 1336-1345
Chen, Q., Bates, A.M., Hanquier, J. N., Simpson, E., Rusch, D. B., Podichit, R., Liu, Y., Wek, R.C., Cornett, E. M., and Georgiadis, M.M. (2022) Structure and genome-wide anlysses suggest that transposon-derived portein SETMAR alters transcription and splicing. J. Biol. Chem. 298, DOI: 10.1016/j.jbc.2022.101894
For a complete list of publications, visit PubMedTitles & Appointments
- Professor of Biochemistry & Molecular Biology
- Professor of Chemistry, School of Science
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Education
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Research