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 Patrick M. Lombardi, Ph.D.

Patrick Lombardi, Ph.D.

Associate Professor of Chemistry

Department of Science

Coad Science Building
Room 210A

+ (301) 447-5746
Patrick Lombardi, Ph.D., received his Bachelor of Science degree in chemistry from Yale University in 2006. He went on to earn his doctoral degree in chemistry from the University of Pennsylvania under the guidance of Professor David W. Christianson. While in the Christianson Laboratory, Lombardi used X-ray crystallography to determine the three-dimensional structures of several bacterial metalloenzymes, including a polyamine deacetylase and a terpene cyclase.

Lombardi joined the laboratory of Professor Cynthia Wolberger at the Johns Hopkins University School of Medicine in 2012 where his research focused on understanding the structural basis of ubiquitin signaling in the DNA damage response. At the Mount, Lombardi works with undergraduate researchers to study ubiquitin signaling using a combination of biochemistry, biophysics, and structural biology.

Postdoctoral fellow, Johns Hopkins University School of Medicine (2012-2017)

Postdoctoral fellow, Yale University (2011-2012)

Ph.D. Chemistry, University of Pennsylvania (2011)

B.S. Chemistry, Yale University (2006)

National Institutes of Health Academic Research Enhancement Award (2020-23)

American Cancer Society Postdoctoral Fellowship Award (2015-16)

National Cancer Center Postdoctoral Fellowship Award (2014)


Protein structure and function

Courses Taught

BIOCH 405, Biochemistry I, BIOL 410 Seminar, CHEM 101 General Chemistry Lecture and Lab, CHEM 102 General Chemistry Lecture and Lab, CHEM 410 Seminar

Research Interests

Our research focuses on understanding how the protein ubiquitin is used to communicate cellular messages. Ubiquitin is a unique type of protein that can be covalently attached to other proteins, including other ubiquitins to form polyubiquitin chains. Each ubiquitin has eight attachment points allowing for an incredible diversity of polyubiquitin chain topologies. Different polyubiquitin chain types have unique three-dimensional structures that are recognized by distinct cellular components from different signaling pathways. By controlling the linkage types within polyubiquitin chains, cells can communicate a large variety of messages using the ubiquitin code. Our lab uses biochemistry, biophysics, and structural biology to understand how different polyubiquitin chains are recognized by their respective binding partners, with specific emphasis on ubiquitin signaling in the DNA damage response.

Anoh R, Burke KA, Schmelyun DP, Lombardi PM: Generation of Monoubiquitin and K63-Linked Polyubiquitin Chains for Protein Interaction Studies. Methods Mol Biol 2022, 2444:271-282.

Lombardi PM, Haile S, Rusanov T, Rodell R, Anoh R, Baer JG, Buke KA, Gray LN, Hacker AR, Kebreau KK, Ngandu CK, Orland HA, Osei-Asante E, Schmelyun DP, Shorb DE, Syed SH, Veilleux JM, Majumdar A, Mosammaparast N, Wolberger C: The ASCC2 CUE domain in the ALKBH3-ASCC DNA repair complex recognizes adjacent ubiquitins in K63-linked polyubiquitin. J Biol Chem 2022, 298:101545.

Bricker JR, Soll JM, Lombardi PM, Vagbo CM, Mudge MC, Oyeniran C, Rabe R, Jackson J, Sullender ME, Blazosky EM, Byrum AK, Zhao Y, Corbett MA, Gecz J, Field M, Vindigni A, Slupphaug G, Wolberger C, Mosammaparast N: A ubiquitin-dependent signaling axis specific for ALKBH3-mediated DNA dealkylation repair. Nature 2017, 7680:389-393.

Lombardi PM, Matunis MJ, Wolberger C: RAP80, ubiquitin and SUMO in the DNA damage response. J Mol Med 2017, 95:799-807.

Harris GG, Lombardi PM, Pemberton TA, Matsui T, Weiss TM, Cole KE, Kšksal M, Murphy FV, Vedula LS, Chou WK, Cane DE, Christianson DW: Structural Studies of Geosmin Synthase, a Bifunctional Sesquiterpene Synthase with Alpha-Alpha Domain Architecture that Catalyzes a Unique Cyclization-Fragmentation Reaction Sequence. Biochemistry 2015, 54:7142-7155.

Wiener R, DiBello AT, Lombardi PM, Guzzo CM, Zhang X, Matunis MJ, Wolberger C: E2 ubiquitin-conjugating enzymes regulate the deubiquitinating activity of OTUB1. Nat Struct Mol Biol 2013, 20:1033-39.

Deardorff MA, Bando M, Nakato R, Watrin E, Itoh T, Minamino M, Saitoh K, Komata M, Katou Y, Clark D, Cole KE, De Baere E, Decroos C, Di Donato N, Ernst S, Francey LJ, Gyftodimou G, Hirashima K, Hullings M, Ishikawa Y, Jaulin C, Kaur M, Kiyono T, Lombardi PM, Magnaghi-Jaulin L, Mortier GR, Nozaki N, Petersen MB, Seimiya H, Siu VM, Suzuki Y, Takagaki K, Wilde JJ, Willems PJ, Prigent C, Gillessen-Kaesbach G, Christianson DW, Kaiser FJ, Jackson LG, Hirota T, Krantz ID, Shirahige K: HDAC8 mutations in Cornelia de Lange Syndrome affect the cohesin acetylation cycle. Nature 2012, 489:313-317.

Ilies M, Dowling DP, Lombardi PM, Christianson DW: Synthesis of a new trifluoroketone analogue of L-arginine and contrasting inhibitory activity against human arginase I and histone deacetylase 8. Bioorg Med Chem Lett 2011, 21:5854-5858.

Lombardi PM, Cole KE, Dowling DP, Christianson DW: Structure, mechanism, and inhibition of histone deacetylases and related metalloenzymes. Curr Opin Struct Biol 2011, 21:735-743.

Lombardi PM, Angell HD, Whittington DA, Flynn EF, Rajashankar KR, Christianson DW: Structure of prokaryotic polyamine deacetylase reveals evolutionary functional relationships with eukaryotic histone deacetylases. Biochemistry 2011, 50:1808-1817.