Monica Pillon Ph.D.
Monica Pillon
Ph.D.
Assistant Professor
Department of Structural Biology
Jacobs School of Medicine & Biomedical Sciences
Specialty/Research Focus
Gene Expression; Metalloenzymes; Mitochondria; Molecular and Cellular Biology; Molecular Basis of Disease; Protein Function and Structure; RNA; Structural Biology
Professional Summary:
Dysregulation of gene expression is a universal feature of disease that drives pathogenic phenotypes and patient outcomes. A central determinant of gene expression is mRNA abundance, highlighting the delicate balance of RNA synthesis, processing, and decay. Ribonucleases are central players in RNA processing and decay pathways. However, the role of the 122+ annotated human ribonucleases in health and disease remains largely unexplored. This is compounded by a limited understanding of the mechanisms that govern ribonuclease RNA selectivity and activation. My lab leads a multidisciplinary research program that combines RNA-protein biochemistry, enzymology, structural biology (e.g. cryo-EM), and cell biology. Our program provides a framework to understand how ribonucleases support cellular homeostasis and dysregulate gene expression in disease. Our long-term goal is to provide a foundation for the translational science community in studying and drugging this new class of therapeutic targets.
Education and Training:
- Fellowship, National Institute of Environmental Health Sciences (NIEHS/NIH) (2020)
- Fellowship, McMaster University (2015)
- PhD, Biochemistry and Biomedical Sciences, McMaster University (2014)
Employment:
- Assistant Professor, Structural Biology, University at Buffalo (2024-present)
- Assistant Professor, Biochemistry and Molecular Pharmacology, Baylor College of Medicine (2021–2024)
Awards and Honors:
- NIEHS Paper of the Year (2021)
- RiboClub's Best Micro-talk Award (2020)
- Governor General’s Academic Gold Medal (2014)
- NIEHS Fellow of the Year (2018)
- International Union of Crystallography's Poster Award (2014)
Research Expertise:
- Cell Biology: Using model human cell lines, we perturb discrete RNA processing signals to determine their importance in gene regulation and cell function.
- Enzymology: We harness the power of enzyme studies to discover the mechanism of action of ribonucleases and the role of their regulatory partners.
- Integrated Structural Biology: We combine structural approaches such as cryo Electron Microscopy (CryoEM), X-ray crystallography, and chemical crosslinking mass spectrometry to reveal the architecture of RNA processing machines in action.
- Reconstitution of Ribonucleoprotein Assemblies: Our lab specializes in the production and assembly of historically refractory RNA processing molecular machines.
Journal Articles:
- Meena JK, Wang JH, Neill NJ, Keough D, Putluri N, Katsonis P, Koire AM, Lee H, Bowling EA, Tyagi S, Orellana M, Dominguez-Vidaña R, Li H, Eagle K, Danan C, Chung HC, Yang AD, Wu W, Kurley SJ, Ho BM, Zoeller JR, Olson CM, Meerbrey KL, Lichtarge O, Sreekumar A, Dacso CC, Guddat LW, Rejman D, Hocková D, Janeba Z, Simon LM, Lin CY, Pillon MC, Westbrook TF. (2024) MYC Induces Oncogenic Stress through RNA Decay and Ribonucleotide Catabolism in Breast Cancer. Cancer discovery (Sep), 14(9): 1699-1716. doi:10.1158/2159-8290.CD-22-0649
- Frazier MN, Dillard LB, Krahn JM, Perera L, Williams JG, Wilson IM, Stewart ZD, Pillon MC, Deterding LJ, Borgnia MJ, Stanley RE. (2021) Characterization of SARS2 Nsp15 nuclease activity reveals it's mad about U. Nucleic acids research (Sep), 49(17): 10136-10149. doi:10.1093/nar/gkab719
- Frazier MN, Pillon MC, Kocaman S, Gordon J, Stanley RE. (2021) Structural overview of macromolecular machines involved in ribosome biogenesis. Current opinion in structural biology (Apr), 67: 51-60. doi:10.1016/j.sbi.2020.09.003
- Pillon MC, Gordon J, Frazier MN, Stanley RE. (2021) HEPN RNases - an emerging class of functionally distinct RNA processing and degradation enzymes. Critical reviews in biochemistry and molecular biology (Feb), 56(1): 88-108. doi:10.1080/10409238.2020.1856769
- Pillon MC, Frazier MN, Dillard LB, Williams JG, Kocaman S, Krahn JM, Perera L, Hayne CK, Gordon J, Stewart ZD, Sobhany M, Deterding LJ, Hsu AL, Dandey VP, Borgnia MJ, Stanley RE. (2021) Cryo-EM structures of the SARS-CoV-2 endoribonuclease Nsp15 reveal insight into nuclease specificity and dynamics. Nature communications (Jan), 12(1): 636. doi:10.1038/s41467-020-20608-z
- Pillon MC, Frazier MN, Dillard LB, Williams JG, Kocaman S, Krahn JM, Perera L, Hayne CK, Gordon J, Stewart ZD, Sobhany M, Deterding LJ, Hsu AL, Dandey VP, Borgnia MJ, Stanley RE. (2020) Cryo-EM Structures of the SARS-CoV-2 Endoribonuclease Nsp15. bioRxiv : the preprint server for biology (Aug). doi:10.1101/2020.08.11.244863
- Pillon MC, Goslen KH, Gordon J, Wells ML, Williams JG, Stanley RE. (2020) It takes two (Las1 HEPN endoribonuclease domains) to cut RNA correctly. The Journal of biological chemistry (May), 295(18): 5857-5870. doi:10.1074/jbc.RA119.011193
- Pillon MC, Stanley RE. (2020) Nonradioactive Assay to Measure Polynucleotide Phosphorylation of Small Nucleotide Substrates. Journal of visualized experiments : JoVE (May)(159). doi:10.3791/61258
- Gordon J, Pillon MC, Stanley RE. (2019) Nol9 Is a Spatial Regulator for the Human ITS2 Pre-rRNA Endonuclease-Kinase Complex. Journal of molecular biology (Sep), 431(19): 3771-3786. doi:10.1016/j.jmb.2019.07.007
- Pillon MC, Lo YH, Stanley RE. (2019) IT'S 2 for the price of 1: Multifaceted ITS2 processing machines in RNA and DNA maintenance. DNA repair (Sep), 81: 102653. doi:10.1016/j.dnarep.2019.102653
- Pillon MC, Hsu AL, Krahn JM, Williams JG, Goslen KH, Sobhany M, Borgnia MJ, Stanley RE. (2019) Cryo-EM reveals active site coordination within a multienzyme pre-rRNA processing complex. Nature structural & molecular biology (Sep), 26(9): 830-839. doi:10.1038/s41594-019-0289-8
- Almawi AW, Scotland MK, Randall JR, Liu L, Martin HK, Sacre L, Shen Y, Pillon MC, Simmons LA, Sutton MD, Guarné A. (2019) Binding of the regulatory domain of MutL to the sliding ß-clamp is species specific. Nucleic acids research (May), 47(9): 4831-4842. doi:10.1093/nar/gkz115
- Mok MCY, Campalans A, Pillon MC, Guarné A, Radicella JP, Junop MS. (2019) Identification of an XRCC1 DNA binding activity essential for retention at sites of DNA damage. Scientific reports (Feb), 9(1): 3095. doi:10.1038/s41598-019-39543-1
- Liu L, Ortiz Castro MC, Rodríguez González J, Pillon MC, Guarné A. (2019) The endonuclease domain of Bacillus subtilis MutL is functionally asymmetric. DNA repair (Jan), 73: 1-6.
- Pillon MC, Sobhany M, Stanley RE. (2018) Characterization of the molecular crosstalk within the essential Grc3/Las1 pre-rRNA processing complex. RNA (New York, N.Y.) (May), 24(5): 721-738. doi:10.1261/rna.065037.117
- Pillon MC, Stanley RE. (2018) Nuclease integrated kinase super assemblies (NiKs) and their role in RNA processing. Current genetics (Feb), 64(1): 183-190. doi:10.1007/s00294-017-0749-9
- Lo YH, Pillon MC, Stanley RE. (2018) Combining X-Ray Crystallography with Small Angle X-Ray Scattering to Model Unstructured Regions of Nsa1 from S. Cerevisiae. Journal of visualized experiments : JoVE (Jan)(131). doi:10.3791/56953
- Pillon MC, Guarné A. (2017) Complementary uses of small angle X-ray scattering and X-ray crystallography. Biochimica et biophysica acta. Proteins and proteomics (Nov), 1865(11 Pt B): 1623-1630.
- Pillon MC, Sobhany M, Borgnia MJ, Williams JG, Stanley RE. (2017) Grc3 programs the essential endoribonuclease Las1 for specific RNA cleavage. Proceedings of the National Academy of Sciences of the United States of America (Jul), 114(28): E5530-E5538. doi:10.1073/pnas.1703133114
- Lo YH, Romes EM, Pillon MC, Sobhany M, Stanley RE. (2017) Structural Analysis Reveals Features of Ribosome Assembly Factor Nsa1/WDR74 Important for Localization and Interaction with Rix7/NVL2. Structure (London, England : 1993) (May), 25(5): 762-772.e4. doi:10.1016/j.str.2017.03.008
- Wan LC, Pillon MC, Thevakumaran N, Sun Y, Chakrabartty A, Guarné A, Kurinov I, Durocher D, Sicheri F. (2016) Structural and functional characterization of KEOPS dimerization by Pcc1 and its role in t6A biosynthesis. Nucleic acids research (Aug), 44(14): 6971-80. doi:10.1093/nar/gkw542
- Stogios PJ, Cox G, Spanogiannopoulos P, Pillon MC, Waglechner N, Skarina T, Koteva K, Guarné A, Savchenko A, Wright GD. (2016) Rifampin phosphotransferase is an unusual antibiotic resistance kinase. Nature communications (Apr), 7: 11343. doi:10.1038/ncomms11343
- Lenhart JS, Pillon MC, Guarné A, Biteen JS, Simmons LA. (2016) Mismatch repair in Gram-positive bacteria. Research in microbiology (Jan), 167(1): 4-12.
- Pillon MC, Babu VM, Randall JR, Cai J, Simmons LA, Sutton MD, Guarné A. (2015) The sliding clamp tethers the endonuclease domain of MutL to DNA. Nucleic acids research (Dec), 43(22): 10746-59. doi:10.1093/nar/gkv918
- Zeqiraj E, Tian L, Piggott CA, Pillon MC, Duffy NM, Ceccarelli DF, Keszei AF, Lorenzen K, Kurinov I, Orlicky S, Gish GD, Heck AJ, Guarné A, Greenberg RA, Sicheri F. (2015) Higher-Order Assembly of BRCC36-KIAA0157 Is Required for DUB Activity and Biological Function. Molecular cell (Sep), 59(6): 970-83. doi:10.1016/j.molcel.2015.07.028
- Huang H, Zeqiraj E, Dong B, Jha BK, Duffy NM, Orlicky S, Thevakumaran N, Talukdar M, Pillon MC, Ceccarelli DF, Wan LC, Juang YC, Mao DY, Gaughan C, Brinton MA, Perelygin AA, Kourinov I, Guarné A, Silverman RH, Sicheri F. (2014) Dimeric structure of pseudokinase RNase L bound to 2-5A reveals a basis for interferon-induced antiviral activity. Molecular cell (Jan), 53(2): 221-34. doi:10.1016/j.molcel.2013.12.025
- Lenhart JS, Pillon MC, Guarné A, Simmons LA. (2013) Trapping and visualizing intermediate steps in the mismatch repair pathway in vivo. Molecular microbiology (Nov), 90(4): 680-98.
- Pillon MC, Dubinsky M, Johnston RN, Liu SL, Guarné A. (2013) Characterization of the defects in the ATP lid of E. coli MutL that cause transient hypermutability. DNA repair (Oct), 12(10): 864-9.
- Pillon MC, Miller JH, Guarné A. (2011) The endonuclease domain of MutL interacts with the ß sliding clamp. DNA repair (Jan), 10(1): 87-93. doi:10.1016/j.dnarep.2010.10.003
- Pillon MC, Lorenowicz JJ, Uckelmann M, Klocko AD, Mitchell RR, Chung YS, Modrich P, Walker GC, Simmons LA, Friedhoff P, Guarné A. (2010) Structure of the endonuclease domain of MutL: unlicensed to cut. Molecular cell (Jul), 39(1): 145-51. doi:10.1016/j.molcel.2010.06.027
Books and Book Chapters:
- Schellenberg MJ, Maheshwari S, Pillon MC. (2022) In: Recombinant Protein Production Using Mammalian Expression Systems. Encyclopedia of Cell Biology. Second Edition.