Daniel Dempsey, PhD

Assistant Professor of Dermatology


Summary

The mission of our lab is to understand the basic biological mechanisms of proteins that are essential to human health and disease. Our lab focuses on investigating the structure, function, and regulation of proteins involved in cell signaling, epigenetics, and gene regulation. We use chemical, semi-synthetic, biophysical, and cellular approaches to elucidate mechanisms for how post-translational modifications regulate protein function. We are also interested in advancing new chemical strategies to investigate PTMs and protein function.

Our current focus is on understanding the function and regulation of deubiquitinases and RNA-modifying proteins, which are emerging as attractive therapeutic targets in several cancers. Our work will shed light on the mechanistic consequence of PTMs, and how dysregulation of these proteins may lead to disease. Our goal is that these findings will pave the way for the rational design of new therapies for the treatment of cancer.


Research Interests

  • Chemical Biology
  • Enzymology
  • Regulatory Mechanisms of PTMs
  • Protein Semi-synthesis
  • Biophysics
  • Cancer Biology
  • Epigenetics and Gene Regulation


Education

  • 12/2004 BA – State University of New York at Oswego, Oswego, NY; Chemistry
  • 5/2007 MS – State University of New York at Oswego, Oswego, NY; Chemistry
  • 5/2015 PhD – University of South Florida, Tampa, FL; Chemistry/Biochemistry
  • 4/2015-9/2017 – Post Doc in Chemical Biology, Philip Cole, Johns Hopkins University, Baltimore, MD
  • 09/2017-9/2021 – Post Doc in Chemical Biology, Philip Cole, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA


Publications

  1. Ivkovic M, Dempsey DR, Handa S, Hilton JH, Lowe EW Jr, Merkler DJ†. N-acylethanolamines as novel alcohol dehydrogenase 3 substrates. Biochem. Biophys. 2011;506:157-64. PMID: 21144815; PMCID: PMC3030644
  2. Bendinskas K†, Sattelberg P, Crossett D, Banyikwa A, Dempsey D, MacKenzie JA. Enzymatic detection of γ-hydroxybutyrate using aldo-keto reductase 7A2. Forensic Sci. 2011;56:783-7. PMID: 21521220
  3. Handa S, Spradling TJ, Dempsey DR, Merkler DJ†. Production of the catalytic core of human peptidylglycine α-hydroxylating monooxygenase (hPHMcc) in Escherichia coli. Protein Expression and Purif. 2012;84:9-13. PMID: 2255482; PMCID: PMC3614408
  4. Jeffries KA, Dempsey DR, Behari AL, Anderson RL, Merkler DJ†. Drosophila melanogaster as a model system to study long chain fatty acid amide metabolism. FEBS Lett. 2014;588:1596-602. PMID: 24650760; PMCID: PMC4023565
  5. Dempsey DR, Bond JD, Carpenter AM, Rodriguez Ospina S, Merkler DJ†. Expression, purification, and characterization of mouse glycine N-acyltransferase (mGLYAT) in Escherichia coli. Protein Expression and Purif. 2014;97:23-8. PMID: 24576660; PMCID: PMC3985065
  6. Dempsey DR, Jeffries KA, Bond JD, Carpenter AM, Rodriguez Ospina S, Caswell KK, Merkler DJ†. Mechanistic and structural analysis of Drosophila melanogaster arylalkylamine N-acetyltransferase. Biochemistry 2014;53:7777-93. PMID: 25406072; PMCID: PMC4270386
  7. Dempsey DR*, Jeffries KA*, Anderson RL, Carpenter AM, Rodriguez Ospina S, Merkler DJ†. Identification of an arylalkylamine N-acyltransferase from Drosophila melanogaster that catalyzes the formation of long-chain N-acylserotonins. FEBS Lett. 2014;588:594-99. PMID: 24650760; PMCID: PMC3952154
  8. Dempsey DR, Jeffries KA, Carpenter AM, Rodriguez Ospina S, Merkler DJ†. Mechanistic and structural evaluation of a Drosophila melanogaster enzyme, arylalkylamine N-acetyltransferase like 7, that catalyzes the formation of N-acetylarylalkylamides and N-acetylhistamine. Biochemistry 2015;54:2644-58. PMID: 25850002; PMCID: PMC4749145
  9. Taylor MS, Dempsey DR, Hwang Y, Chen Z, Chu N, Boeke JD, Cole PA†. Mechanistic analysis of ghrelin-O-acyltransferase using substrate analogs. Chem. 2015;62:64-73. PMID: 26246082; PMCID: PMC4567917
  10. Dempsey DR, Carpenter AM, Rodriguez Ospina S, Merkler DJ†. Probing the chemical mechanism and critical regulatory residues of Drosophila melanogaster arylalkylamine N-acyltransferase like 2. Insect Biochem. Mol. Biol. 2015;66:1-12. PMID: 26476413; PMCID: PMC4663176
  11. Jeffries KA, Dempsey DR, Farrell EK, Garbade GJ, Gurina T, Gruhonjic I, Merkler DJ†. Glycine N-acyltransferase like 3 is responsible for long-chain N-acylglycine formation in N18TG2 cells. Lipid. Res. 2016;57:781-91. PMID: 27016726; PMCID: PMC4847626
  12. Chen Z*, Dempsey DR*, Thomas SN, Hayward D, Bolduc DM, Cole PA†. Molecular features of phosphatase and tensin homolog (PTEN) regulation by C-terminal phosphorylation. Biol. Chem. 2016;291:14160-69. PMID: 27226612; PMCID: PMC4933174
  13. Henager S, Chu N, Chen Z, Bolduc D, Dempsey DR, Hwang Y, Wells J, Cole PA†. Enzyme-catalyzed express protein ligation. Methods 2016;11:925-27. PMID: 27669326; PMCID: PMC5088058
  14. Chen Z, Jiang H, Wei X, Li X, Dempsey DR, Zhang X, Devreotes P, Wolberger C, Amzel M, Gabelli S†, Cole PA†. A tunable brake for HECT ubiquitin ligases. Cell 2017;66:345-57. PMID: 28475870; PMCID: PMC5489419
  15. Dempsey DR, Nichols DA, Battistini MA, Pemberton O, Rodriguez-Ospina S, Zhang X, Carpenter AM, Chen Y, Merkler DJ†. Structural and mechanistic analysis of Drosophila melanogaster agmatine N-acetyltransferase, an enzyme that catalyzes the formation of N-acetylagmatine. Rep. 2017;7:13432. PMID: 29044148; PMCID: PMC5647378
  16. Handa S, Dempsey DR, Ramamoorthy D, Cook N, Guida WC, Spradling TJ, White JK, Woodcock HL, Merkler DJ†. Mechanistic studies of 1-deoxy-D-xylulose-5-phosphate synthase from Deinococcus radiodurans. Mol. Biol. J. 2018;4: Epub. PMID: 30149868; PMCID: PMC5851014
  17. Dempsey DR, Jiang H, Kalin JH, Chen Z, Cole PA†. Site-specific protein labeling with N-hydroxysuccinimide-esters and the analysis of ubiquitin ligase mechanisms. Am. Chem. Soc. 2018;140:9374-8. PMID: 30016585; PMCID: PMC6093203
  18. Chu N, Salguero AL, Chen Z, Dempsey DR, Ficaroo SB, Alexander WM, Marto JA, Li Y, Amzel LM, Gabelli SB†, Cole PA†. Akt kinase activation mechanisms revealed using protein semisynthesis. Cell 2018;174:897-907. PMID: 30078705; PMCID: PMC6139374
  19. Henager SH, Henriquez S, Dempsey DR, Cole PA†. Analysis of site-specific phosphorylation of PTEN by using enzyme-catalyzed expressed protein ligation. 2020;21:64-8. PMID: 31206229; PMCID: PMC7012368
  20. Jiang H, Dempsey DR, Cole PA†. Ubiquitin ligase activities of WWP1 germline variants K740N and N745S. 2021;639:357-64. PMID: 32475408; PMCID: PMC7340118.
  21. Dempsey DR*, Viennet T*, Iwase R, Park E, Henriquez S, Chen Z, Jeliazkov JR, Palanski BA, Phan KL, Coote P, Gray JJ, Eck MJ, Gabelli SB†, Arthanari H†, Cole PA†. The structural basis of PTEN regulation by multi-site phosphorylation. Struct. Mol. Biol. (accepted)

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