Personal Summary

The overall research areas in my laboratory are molecular virology, host-virus interactions, and cellular antiviral and inflammatory pathways.  In particular, we study how mammalian cells respond to  Rift Valley fever virus infection, and how the virus evades the cellular antiviral and inflammatory reactions to infection.  We investigate the roles of RNA structural motifs within viral genomes and host mRNAs during viral packaging, translation, and splicing, and during the host cell's response to infection.  Enhanced understanding of these essential processes will lead to potential novel antiviral therapeutic strategies.  Furthermore, understanding how viruses suppress cellular immune responses to infection will inform novel strategies to combat autoimmune and autoinflammatory diseases.

Education

B.S. Chemistry, University of Montana 1985
M.S. Biochemistry, University of Montana, 1991
Ph.D. Biology, Brown University, 1996

Post-doctoral: Université Louis Pasteur, Strasbourg, France 1996-1999

 

Courses Taught

BCH294 (with others, spring semesters)

BCH480 Advanced Biochemistry I (fall 2020)

BCH482 Advanced Biochemistry II (every spring semester)

BCH561 RNA Structure and Function (every semester)

BCH584 Nucleic Acids  (fall semesters- odd numbered years)

BCH380 Fundamentals of Biochemistry (fall semesters- even numbered years)

Research Interests

My research interests lie in the mechanisms of molecular recognition between biological macromolecules. In particular, I am interested in RNA-protein and protein-protein interactions as they relate to viral replication and the cellular immune response to infection. Interfering with these essential interactions during viral replication represents a potential avenue for antiviral drug development.

Rift Valley fever virus (RVFV) is a mosquito borne pathogen that is endemic to Africa, but has the potential for spread outside its historical boundaries due to increased global trade and changing climate patterns. The virus causes disease in humans and livestock. In humans, symptoms range from a mild flu-like illness to severe hemorrhagic fever. So far there are no proven treatments or vaccines to combat or prevent the disease. 

RVFV nucleocapsid protein, N, has several known functions during replication, including roles in encapsidation, packaging, translational control, and regulating the balance between genomic and antigenomic viral RNA synthesis in infected cells. Each of these functions is crucial for the virus to propagate successfully and each involves interactions with RNA. We are striving to understand at the molecular level how N recognizes viral RNA.  We are also endeavoring to identify small molecule inhibitors of this interaction that could be developed into drugs to treat humans and/or livestock that are infected with RVFV.

Field of Study

Molecular virology and RNA biochemistry

Selected Publications

Bisom, T. C.; Smelser, H.; Lanchy, J. M.; Lodmell, J. S., Alternative splicing of RIOK3 engages the noncanonical NFκB pathway during Rift Valley fever virus infection. Viruses 2023, 15, (7), 1566.

Diaz, M.; Diaz, M.; Kreitinger, J.; Bisom, T. C.; Lodmell, J. S.; Diaz, P., Targeting right open reading frame protein kinase 3 (RIOK3) for the modulation of type III IFN in skin. Journal of Investigative Dermatology 2023, 143, (5), S187.

Bisom, T. C.; White, L. A.; Lanchy, J. M.; Lodmell, J. S., RIOK3 and Its Alternatively Spliced Isoform Have Disparate Roles in the Innate Immune Response to Rift Valley Fever Virus (MP12) Infection. Viruses 2022, 14, (9).

White, L. A.; Bisom, T. C.; Grimes, H. L.; Hayashi, M.; Lanchy, J. M.; Lodmell, J. S., Tra2beta-Dependent Regulation of RIO Kinase 3 Splicing During Rift Valley Fever Virus Infection Underscores the Links Between Alternative Splicing and Innate Antiviral Immunity. Front Cell Infect Microbiol 2022, 11, 799024.

Hayashi, M.; Schultz, E. P.; Lanchy, J. M.; Lodmell, J. S., Time-Resolved Analysis of N-RNA Interactions during RVFV Infection Shows Qualitative and Quantitative Shifts in RNA Encapsidation and Packaging. Viruses 2021, 13, (12), 2417.

Havranek KE, White LA, Bisom TC, Lanchy JM, Lodmell JS (2021) The Atypical Kinase RIOK3 Limits RVFV Propagation and Is Regulated by Alternative Splicing. Viruses:13(3). 

Stamm S, Lodmell JS (2019) C/D box snoRNAs in viral infections: RNA viruses use old dogs for new tricks. Non-coding RNA Research 4: 46-53.

Havranek KE, White LA, Lanchy JM, Lodmell JS (2019) Transcriptome profiling in Rift Valley fever virus infected cells reveals modified transcriptional and alternative splicing programs. PloS one 14: e0217497.

Hornak KE, Lanchy JM, Lodmell JS (2016) RNA Encapsidation and Packaging in the Phleboviruses. Viruses 8: 194-208.

Ellenbecker, M, St Goddard, J, Sundet, A, Lanchy, JM,Raiford, D, Lodmell, JS (2015) Computational prediction and biochemical characterization of novel RNA aptamers to Rift Valley fever virus nucleocapsid protein. Comput Biol Chem, 58, 120-5.

Ellenbecker, M, Lanchy, JM, Lodmell, JS (2014) Inhibition of Rift Valley fever virus replication and perturbation of nucleocapsid-RNA interactions by suramin. Antimicrob Agents Chemother, 58, (12), 7405-15.

Ellenbecker M, Lanchy JM, Lodmell JS (2012) Identification of Rift Valley fever virus nucleocapsid protein-RNA binding inhibitors using a high-throughput screening assay. Journal of biomolecular screening 17: 1062-1070. PMCID: PMC3520603.

Ellenbecker M, Sears L, Li P, Lanchy JM, Lodmell JS (2012) Characterization of RNA aptamers directed against the nucleocapsid protein of Rift Valley fever virus. Antiviral Res 93: 330-339. PMCID: PMC3299919.

Wright BE, Schmidt KH, Hunt AT, Lodmell JS, Minnick MF, Reschke DK (2011) The roles of transcription and genotoxins underlying p53 mutagenesis in vivo. Carcinogenesis 32: 1559-1567. PMCID: PMC3179427.

Strong CL, Lanchy JM, Lodmell JS. Viral SELEX reveals individual and cooperative roles of the C-box and G-box in HIV-2 replication. RNA. 2011;17(7):1307-20. PMCID: 3138567.

Strong CL, Lanchy JM, Dieng-Sarr A, Kanki PJ, Lodmell JS. A 5'UTR-Spliced mRNA Isoform Is Specialized for Enhanced HIV-2 gag Translation. J Mol Biol. 2009;391(2):426-37. PMCID: PMC2750851.

Baig TT, Lanchy JM, Lodmell JS. Randomization and in vivo selection reveal a GGRG motif essential for packaging human immunodeficiency virus type 2 RNA. J Virol. 2009;83(2):802-10. PMCID: PMC2612376.

Baig TT, Strong CL, Lodmell JS, Lanchy JM. Regulation of primate lentiviral RNA dimerization by structural entrapment. Retrovirology. 2008;5:65. PMCID: PMC2494553.

Lanchy JM, Lodmell JS. An extended stem-loop 1 is necessary for human immunodeficiency virus type 2 replication and affects genomic RNA encapsidation. J Virol. 2007;81(7):3285-92. PMCID: PMC1866085.

Fabbretti A, Pon CL, Hennelly SP, Hill WE, Lodmell JS, Gualerzi CO. The real-time path of translation factor IF3 onto and off the ribosome. Mol Cell. 2007;25(2):285-96.

Baig TT, Lanchy JM, Lodmell JS. HIV-2 RNA dimerization is regulated by intramolecular interactions in vitro. RNA. 2007;13(8):1341-54. PMCID: PMC1924897.

Criswell D, Tobiason VL, Lodmell JS, Samuels DS. Mutations conferring aminoglycoside and spectinomycin resistance in Borrelia burgdorferi. Antimicrob Agents Chemother. 2006;50(2):445-52. PMCID: PMC1366916.

Knight W, Hill W, Lodmell JS. Ribosome builder: a software project to simulate the ribosome. Comput Biol Chem. 2005;29(2):163-74.

Hennelly SP, Antoun A, Ehrenberg M, Gualerzi CO, Knight W, Lodmell JS, et al. A time-resolved investigation of ribosomal subunit association. J Mol Biol. 2005;346(5):1243-58.

Bowen WS, Van Dyke N, Murgola EJ, Lodmell JS, Hill WE. Interaction of thiostrepton and elongation factor-G with the ribosomal protein L11-binding domain. J Biol Chem. 2005;280(4):2934-43.

RNASocietyNews. Annual RNA/Scaringe Award Presented to Stefano Marzi. RNA. 2004;10(8):1036.

Lanchy JM, Szafran QN, Lodmell JS. Splicing affects presentation of RNA dimerization signals in HIV-2 in vitro. Nucleic Acids Res. 2004;32(15):4585-95. PMCID: PMC516069.

Brandi L, Marzi S, Fabbretti A, Fleischer C, Hill WE, Gualerzi CO, et al. The translation initiation functions of IF2: targets for thiostrepton inhibition. J Mol Biol. 2004;335(4):881-94.

Marzi S, Knight W, Brandi L, Caserta E, Soboleva N, Hill WE, et al. Ribosomal localization of translation initiation factor IF2. RNA. 2003;9(8):958-69. PMCID: PMC1370462.

Lodmell JS, Hennelly SP. Conformational dynamics within the ribosome. In: Lapointe J, Brakier-Gingras L, editors. Translation Mechanisms. Georgetown, TX USA: Kluwer Academic/ Plenum Publishers; 2003. p. 264-79.

Lanchy JM, Rentz CA, Ivanovitch JD, Lodmell JS. Elements located upstream and downstream of the major splice donor site influence the ability of HIV-2 leader RNA to dimerize in vitro. Biochemistry. 2003;42(9):2634-42. PMCID: PMC1473984.

Lanchy JM, Ivanovitch JD, Lodmell JS. A structural linkage between the dimerization and encapsidation signals in HIV-2 leader RNA. RNA. 2003;9(8):1007-18. PMCID: PMC1370466.

Deer EL, Douk B, Lanchy JM, Lodmell JS. Elucidation and characterization of oligonucleotide-accessible sites on HIV-2 leader region RNA. Antisense Nucleic Acid Drug Dev. 2003;13(1):45-55. PMCID: PMC1403296.

Lanchy JM, Lodmell JS. Alternate usage of two dimerization initiation sites in HIV-2 viral RNA in vitro. J Mol Biol. 2002;319(3):637-48. PMCID: PMC1451413.

Lodmell JS, Ehresmann C, Ehresmann B, Marquet R. Structure and dimerization of HIV-1 kissing loop aptamers. J Mol Biol. 2001;311(3):475-90.

Jossinet F, Lodmell JS, Ehresmann C, Ehresmann B, Marquet R. Identification of the in vitro HIV-2/SIV RNA dimerization site reveals striking differences with HIV-1. J Biol Chem. 2001;276(8):5598-604.

Bowen WS, Hill WE, Lodmell JS. Comparison of rRNA cleavage by complementary 1,10-phenanthroline-Cu(II)- and EDTA-Fe(II)-derivatized oligonucleotides. Methods. 2001;25(3):344-50.

Lodmell JS, Ehresmann C, Ehresmann B, Marquet R. Convergence of natural and artificial evolution on an RNA loop-loop interaction: the HIV-1 dimerization initiation site. RNA. 2000;6(9):1267-76. PMCID: PMC1370000.

Jossinet F, Paillart JC, Westhof E, Hermann T, Skripkin E, Lodmell JS, et al. Dimerization of HIV-1 genomic RNA of subtypes A and B: RNA loop structure and magnesium binding. RNA. 1999;5(9):1222-34. PMCID: PMC1369845.

Lodmell JS, Paillart JC, Mignot D, Ehresmann B, Ehresmann C, Marquet R. Oligonucleotide-mediated inhibition of genomic RNA dimerization of HIV-1 strains MAL and LAI: a comparative analysis. Antisense Nucleic Acid Drug Dev. 1998;8(6):517-29.

Gregory ST, Brunelli CA, Lodmell JS, O'Connor M, Dahlberg AE. Genetic selection of rRNA mutations. Methods Mol Biol. 1998;77:271-81.

Lodmell JS, Dahlberg AE. A conformational switch in Escherichia coli 16S ribosomal RNA during decoding of messenger RNA. Science. 1997;277(5330):1262-7.

O'Connor M, Brunelli CA, Firpo MA, Gregory ST, Lieberman KR, Lodmell JS, et al. Genetic probes of ribosomal RNA function. Biochem Cell Biol. 1995;73(11-12):859-68.

Lodmell JS, Gutell RR, Dahlberg AE. Genetic and comparative analyses reveal an alternative secondary structure in the region of nt 912 of Escherichia coli 16S rRNA. Proc Natl Acad Sci U S A. 1995;92(23):10555-9. PMCID: PMC40650.

Lodmell JS, Tapprich WE, Hill WE. Evidence for a conformational change in the exit site of the Escherichia coli ribosome upon tRNA binding. Biochemistry. 1993;32(15):4067-72.

Marconi RT, Lodmell JS, Hill WE. Identification of a rRNA/chloramphenicol interaction site within the peptidyltransferase center of the 50 S subunit of the Escherichia coli ribosome. J Biol Chem. 1990;265(14):7894-9.

 

Affiliations

Primary affiliation: Division of Biological Sciences/CMMB
Program Director: Biochemistry Program (interdepartmental)
Participating faculty in Center for Biomolecular Structure and Dynamics
Participating faculty in Molecular Biosciences (MBS) Umbrella Program

 

 

 

Professional Experience

Post-doctoral Fellow 1996-1999
Institut de Biologie Moléculaire et Cellulaire

Université Louis Pasteur

Strasbourg, France

Visiting Scholar 2006-2007

(Research on Rift Valley fever virus N-RNA interactions, hosted by Prof. Richard Elliott)

The University of St. Andrews

Centre for Biomolecular Sciences

St. Andrews, UK

Visiting Professor June-August 2011

(Research on ribosome structure and function, hosted by Prof. Albert Dahlberg)

Brown University

Providence, RI