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  • Julie Secombe, Ph.D.

Julie Secombe, Ph.D.

Julie Secombe

Professor, Department of Genetics

Professor, Dominick P. Purpura Department of Neuroscience

Area of Research: Chromatin and gene expression; KDM5 histone demethylase-regulated transcription; KDM5-mediated intellectual disability; Myc oncogene-induced growth and genome instability; Linking Myc to activation of transposons and aging.

Contact Information

718.430.2698718.430.8778julie.secombe@einsteinmed.edu

Albert Einstein College of Medicine
Jack and Pearl Resnick Campus

1300 Morris Park Avenue
Ullmann Building, Room 809
Bronx, NY 10461

Research Profiles

More Resources: Secombe Lab Website

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Professional Interests

My lab has a long-term interest in understanding the function of the KDM5 family of transcriptional regulators.  KDM5 proteins have a unique combination of chromatin modifying and recognition domains that are likely to regulate gene expression through distinct mechanisms.  In addition, an ever-growing body of evidence links their dysregulation to human pathologies.  Of the four human KDM5 paralogs (KDM5A-D), three are clinically significant. KDM5A or KDM5B are overexpressed in a large number of cancers, and loss of function mutations in KDM5A, KDM5B and KDM5C are found in patients with X-linked intellectual disability. 

To-date, however, no effective therapies exist to treat disorders caused by KDM5 protein dysfunction, primarily because we do not have a comprehensive knowledge of KDM5 target genes, nor of the mechanisms by which KDM5 proteins regulate gene expression.  To dissect KDM5 function we use Drosophila since it encodes a single, essential, KDM5 ortholog thereby overcoming the complication of functional redundancy among the four mammalian paralogs.

We currently have a number of projects going on in the lab:

  • Examining neuronal phenotypes of kdm5 mutant animals and identifying KDM5 target genes to gain insight into how loss of human KDM5 genes result in intellectual disability. 
  • Generating and characterizing the phentoypes and gene expression changes in fly strains harboring mutations that are analogous to those found in intellectual disability patients. Significantly, all missense mutations in KDM5 genes found in affected patients occur in evolutionarily conserved residues.
  • Defining KDM5 target genes in larvae and in adults and defining the different mechanisms used by KDM5 to activate and repress gene expression. 
  • Determining how KDM5 acts with the oncoprotein Myc to regulate cell growth, as this is likely to be directly relevant to understanding how KDM5A/B causes cancer in humans.

Follow me on twitter @flygirl2308


Selected Publications

For an up to date list:https://www.ncbi.nlm.nih.gov/myncbi/julie.secombe.1/bibliography/public/

Hatch, H.A.M., O’Neill, M.H., Marion, R.W., Secombe, J.#., and L.H. Shulman# (2021) Caregiver-reported characteristics of children diagnosed with pathogenic variants in KDM5C. American Journal of Medical Genetics - Part A, doi:10.1002/amjg.a.62381 PMID:34089235 

Hatch, H.A.M., Belalcazar H.M., Marshall O.J., and Secombe J (2021) A KDM5-Prospero transcriptional axis functions during early neurodevelopment to regulate mushroom body formation. eLife doi.org/10.7554/elife.63886 PMID: 33729157

Belalcazar, H.M., Hendricks, E.L., Zamurrad, S., Liebl, F.L.W., and Secombe J (2021) The histone demethylase KDM5 is required for synaptic structure and function at the Drosophila neuromuscular junction. Cell Reports, 34(7):108753. DOI:10.1016/j.celrep.2021.108753. PMID:33596422

Drelon, D., Rogers, M.F., H. M. Belalcazar, and J. Secombe (2019) The histone demethylase KDM5 controls developmental timing by promoting prothoracic gland endocycles. Development, 146(24)pii:dev182568. PMID:31862793

Chen, K., Luan, X., Liu, Q., Wang, J., ChangX., Snijders A. M., Mao J-H., Secombe J., Dan Z, Chen J-H., Wang Z., Dong X., Qiu C., Chang X., Zhang D., Celniker S. E., and Xingyin Liu (2019) Drosophila KDM5 regulates social behavior through immune control and gut microbiota maintenance. Cell Host & Microbe25, 1-16. PMID:30902578

Drelon, C., Belalcazar, H.M., and J. Secombe (2018) The histone demethylase KDM5 is essential for larval growth in Drosophila. Genetics 209(3):773-787. PMID:29764901

Zamurrad, S., Hatch, H.A.M., Drelon, C., Belalcazar, H.M, and J.Secombe (2018) A Drosophilamodel of intellectual disability caused by mutations in the histone demethylase KDM5. Cell Reports 22, 2359-2369.  PMCID:PMC5854480.

Navarro-Costa, P., McCarthy, A., Prudencio, P., Greer, C., Guilgur, L.G., Becker, J., Secombe, J., Rangan, P and R. Martinho (2016) Early programming of the oocyte epigenome temporally controls late prophase I transcription and chromatin remodelling. Nat. Comms. 10;7:12331.

Liu, X., and J. Secombe (2015) The histone demethylase KDM5 activates gene expression by recognizign chromatin context through its PHD reader motif. Cell Reports, 13:2219-2231.

Liu, X., Greer, C., and J. Secombe (2014) KDM5 interacts with Foxo to modulate cellular levels of oxidative stress. PLos Genetics 10(10): e1004676

Li, L., Anderson, S., Secombe, J and R.N. Eisenman (2013) The Drosophila ubiquitin-specific protease Puffyeye regulates dMyc-mediated growth. Development, 140:1-12.

Greer, C., Lee, M., Westerhof, M., Milholland, B., Spokony, R., Vijg, J. and Secombe, J (2013) Myc-dependent genome instability and lifespan in Drosophila. PLoS ONE, 8(9): e74641.

DiTacchio, L., Le, HD., Vollmers, C., Hatori, M., Witcher, M., Secombe, J. and Panda, P. (2011) Histone lysine demethylase JARID1a activates transcription regulators CLOCK-BMAL1 and influences the circadian clock. Science, 333:1881-1884.

Li, L., C. Greer, R.N. Eisenman and J. Secombe (2010) Essential functions of the histone demethylase Lid. PLoS Genetics 6(11):e1001221.

 

 

 

 

 

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