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Daria A. Gaykalova, PhD

Academic Title:

Associate Professor

Primary Appointment:

Otorhinolaryngology-Head & Neck Surgery

Location:

Health Sciences Facility III, 670 West Baltimore St, Baltimore 21201

Phone (Primary):

410 706 2609

Fax:

410 706 0729

Education and Training

  • B.Sc. in Molecular Biology, Moscow State University, Moscow, Russia, 2004
  • M.Sc. in Molecular Biology (Magna Cum Laude), Moscow State University, Moscow, Russia, 2005
  • Ph.D. in Cellular and Molecular Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ, 2009

Biosketch

As a cancer biologist with a background in pharmacology, the ultimate goal of Dr. Gaykalova is to develop novel cancer therapies, particularly for tumor types that lack effective disease-specific treatment options, such as head and neck squamous cell carcinoma (HNSCC). She heads the translational laboratory, which defines the functional role of epigenetics in the regulation of expression of canonical and alternatively spliced transcripts. Her team has recently characterized the landscape of the cancer-specific alternative splicing events (ASE) in HNSCC and defined their potential role in cancer formation. Moreover, her data suggest that chromatin, and in particular, enhancers, have a regulatory role in the expression of cancer-specific ASE isoforms. The further analysis will help to investigate the interplay between open chromatin and ASE isoform expression, define the role of ASE on cancer formation, and help to determine the detailed functional role of enhancers on the expression of ASE isoforms, which significantly contribute to HNSCC formation. Her work also suggests that both of these processes (alternative isoform expression and chromatin remodeling) can be therapeutically controlled. Such potential therapeutic strategies can form the basis for the development of effective disease-specific therapeutics for this disease and other solid tumors.

Dr. Gaykalova is an expert in the wide variety of biochemical and molecular biology techniques from PCR to in vitro assembly of transcription machinery complexes, as well as cancer and cell biology techniques from gene cloning and transfection to CRISPR and drug treatment of different in vivo and in vitro models, as well as further functional evaluation (cell proliferation, migration, and invasion) of the treated cells. Her group is specialized in the high-throughput analysis of gene expression landscape and chromatin structure in different models and tissue types on both bulk and single-cell level. Dr. Gaykalova has multiple papers documented her expertise bridging the divide between the diversity of such experimental data, high throughput data integration, and robust experimental validation. These and other wet-lab experiences were gained over many years of wet-lab training, practicing, teaching, and leading.

Main scientific discoveries

  • Discovered the detailed mechanism of PolII transcription through chromatin
  • Defined the role of the first transcribed nucleosome in PolII transcription regulation
  • Assigned the role of BORIS transcription factor in HNSCC regulation through epigenetic modulation
  • Described the landscape of alternative splicing in HPV- and HPV+ HNSCC
  • Defined the role of chromatin in HNSCC development and HPV integration
  • Described the role of the NOTCH pathway in HNSCC development
  • Discovered primary DNA methylation markers of HNSCC

 

Research/Clinical Keywords

Mouth squamous cell carcinoma, head and neck cancer, HPV, genomics, cancer epigenetics, chromatin, gene expression, transcription regulation, alternative splicing, epigenetic therapeutics, immune regulation in cancer, immune regulation of tumor development, data integration, genome-wide analysis

Highlighted Publications

Kelley DZ, Flam EL, Izumchenko E, Danilova LV, Wulf HA, Guo T, Singman DA, Bahman A, Skaist A, Considine M, Stavrovskaya E, Bishop JA, Westra WH, Khan Z, Koch WM, Sidransky D, Wheelan S, Favorov AV, Califano JA, Fertig EJ, Gaykalova DA. Integrated analysis of whole-genome ChIP-Seq and RNA-Sequencing data of primary tumor samples associates HPV integration sites with open chromatin marks. Cancer Res. 2017 Sep 25. PMCID: PMC6029614

Kelley DZ, Flam EL, Guo T, Danilova LV, Zamuner F, Bohrson C, Considine M, Windsor EJ, Bishop JA, Zhang C, Koch WM, Sidransky D, Westra WH, Chung CH, Califano JA, Wheelan S, Favorov AV, Florea L, Fertig EJ, Gaykalova DA. Functional characterization of alternatively spliced GSN in head and neck squamous cell carcinoma. Transl Res. 2018 Jul 26. pii: S1931-5244(18)30108-7. doi: 10.1016/j.trsl.2018.07.007. [Epub ahead of print]. PMCID: PMC6218276

Guo T, Zambo KDA, Zamuner FT, Ou T, Hopkins C, Kelley DZ, Wulf HA, Winkler E, Erbe R, Danilova L, Considine M, Sidransky D, Favorov A, Florea L, Fertig EJ, Gaykalova DA. Chromatin structure regulates cancer-specific alternative splicing events in primary HPV-related oropharyngeal squamous cell carcinoma. Epigenetics. 2020 Mar 22:1-13. doi: 10.1080/15592294.2020.1741757. PMID: 32164487

Kagohara LT, Zamuner F, Davis-Marcisak EF, Sharma G, Considine M, Allen J, Yegnasubramanian S, Gaykalova DA*, Fertig EJ*. Integrated single-cell and bulk gene expression and ATAC-seq reveals heterogeneity and early changes in pathways associated with resistance to cetuximab in HNSCC-sensitive cell lines. Br J Cancer. 2020 May 4. doi: 10.1038/s41416-020-0851-5. Online ahead of print.PMID: 32362655. 

 

Additional Publication Citations

  • Bondarenko VA, Steele LM, Ujvári A, Gaykalova DA, Kulaeva OI, Polikanov YS, Luse DS, Studitsky VM. Nucleosomes can form a polar barrier to transcript elongation by RNA polymerase II. Mol Cell. 2006; 24(3):469-479. PMID: 17081995
  • Kulaeva OI, Gaykalova DA, Studitsky VM. Transcription through chromatin by RNA polymerase II: histone displacement and exchange. Mutat Res. 2007; 618(1-2):116-129. PMID: 17313961
  • Gaykalova DA, Kulaeva OI, Bondarenko VA, Studitsky VM. Preparation and analysis of uniquely positioned mononucleosomes. Methods Mol Biol. 2009;523:109-123. doi: 10.1007/978-1-59745-190-1_8. PMID: 19381918
  • Morozov AV, Fortney K, Gaykalova DA, Studitsky VM, Widom J, Siggia ED. Using DNA mechanics to predict in vitro nucleosome positions and formation energies. Nucleic Acids Res. 2009; 37(14):4707-4722. PMID: 19509309
  • Kulaeva OI*, Gaykalova DA*, Pestov NA, Golovastov VV, Vassylyev DG, Artsimovitch I, Studitsky VM. Mechanism of chromatin remodeling and recovery during passage of RNA polymerase II. Nat Struct Mol Biol. 2009; 16(12):1272-1278. PMID: 19935686. *-equal contribution
  • Gaykalova DA, Nagarajavel V, Bondarenko VA, Bartholomew B, Clark DJ, Studitsky VM. A polar barrier to transcription can be circumvented by remodeler-induced nucleosome translocation. Nucleic Acids Res. 2011; 39(9):3520-3528. PMID: 21245049
  • Bhan S, Negi SS, Shao C, Glazer CA, Chuang A, Gaykalova DA, Sun W, Sidransky D, Ha PK, Califano JA. BORIS binding to the promoters of cancer testis antigens, MAGEA2, MAGEA3, and MAGEA4, is associated with their transcriptional activation in lung cancer. Clin Cancer Res. 2011; 17(13):4267-4276. PMID: 21558405
  • Gaykalova DA, Kulaeva OI, Pestov NA, Hsieh FK, Studitsky VM. Experimental analysis of the mechanism of chromatin remodeling by RNA polymerase II. Methods Enzymol. 2012; 512:293-314. doi: 10.1016/B978-0-12-391940-3.00013-5. PMID: 22910212
  • Shao C, Tan M, Bishop JA, Liu J, Bai W, Gaykalova DA, Ogawa T, Vikani AR, Agrawal Y, Li RJ, Kim MS, Westra WH, Sidransky D, Califano JA, Ha P.K. Suprabasin is hypomethylated and associated with metastasis in salivary adenoid cystic carcinoma. PLoS One. 2012; 7(11):e48582. PMID: 23144906
  • Gaykalova D, Vatapalli R, Glazer CA, Bhan S, Shao C, Sidransky D, Ha PK, Califano JA. Dose-dependent activation of putative oncogene SBSN by BORIS. PLoS One. 2012; 7(7):e40389. PMID: 22792300
  • Fertig EJ, Markovic A, Danilova LV, Gaykalova DA, Cope L, Chung CH, Ochs MF, Califano JA. Preferential activation of the hedgehog pathway by epigenetic modulations in HPV negative HNSCC identified with meta-pathway analysis. PLoS One. 2013; 8(11):e78127. PMID: 24223768
  • Li R, Ochs MF, Ahn SM, Hennessey P, Tan M, Soudry E, Gaykalova DA, Uemura M, Brait M, Shao C, Westra W, Bishop J, Fertig EJ, Califano JA. Expression microarray analysis reveals alternative splicing of LAMA3 and DST genes in head and neck squamous cell carcinoma. PLoS One. 2014; 9(3):e91263. PMID: 24675808
  • Gaykalova DA, Mambo E, Choudhary A, Houghton J, Buddavarapu K, Sanford T, Darden W, Adai A, Hadd A, Latham G, Danilova LV, Bishop J, Li RJ, Westra WH, Hennessey P, Koch WM, Ochs MF, Califano JA, Sun W. Novel insight into mutational landscape of head and neck squamous cell carcinoma. PLoS One. 2014; 9(3):e93102. PMID: 24667986
  • Sun W, Gaykalova DA, Ochs MF, Mambo E, Arnaoutakis D, Liu Y, Loyo M, Agrawal N, Howard J, Li R, Ahn S, Fertig E, Sidransky D, Houghton J, Buddavarapu K, Sanford T, Choudhary A, Darden W, Adai A, Latham G, Bishop J, Sharma R, Westra WH, Hennessey P, Chung CH, Califano JA. Activation of the NOTCH pathway in head and neck cancer. Cancer Res. 2014; 74(4):1091-1104. PMID: 24351288
  • Rathi KS, Gaykalova DA, Hennessey P, Califano JA, Ochs MF. Correcting transcription factor gene sets for copy number and promoter methylation variations. Drug Dev Res. 2014; 75(6):343-347. PMID: 25195578
  • Gaykalova DA, Manola JB, Ozawa H, Zizkova V, Morton K, Bishop JA, Sharma R, Zhang C, Michailidi C, Considine M, Tan M, Fertig EJ, Hennessey PT, Ahn J, Koch WM, Westra WH, Khan Z, Chung CH, Ochs MF, Califano JA. NF-κB and stat3 transcription factor signatures differentiate HPV-positive and HPV-negative head and neck squamous cell carcinoma. Int J Cancer. 2015 October 15th; 137(8):1879-89. PMID: 25857630
  • Gaykalova DA, Kulaeva OI, Volokh O, Shaytan AK, Hsieh FK, Kirpichnikov MP, Sokolova OS, Studitsky VM. Structural analysis of nucleosomal barrier to transcription. Proc Natl Acad Sci U S A. 2015 October 27th; 112(43):E5787-95. PMID: 26460019
  • Gaykalova DA, Vatapalli R, Wei Y, Tsai HL, Wang H, Zhang C, Hennessey PT, Guo T, Tan M, Li R, Ahn J, Khan Z, Westra WH, Bishop JA, Zaboli D, Koch WM, Khan T, Ochs MF, Califano JA. Outlier Analysis Defines Zinc Finger Gene Family DNA Methylation in Tumors and Saliva of Head and Neck Cancer Patients. PLoS One. 2015 Nov 6; 10(11):e0142148. PMID: 26544568
  • Stansfield JC, Rusay M, Shan R, Kelton C, Gaykalova DA, Fertig EJ, Califano JA, Ochs MF. Toward Signaling-Driven Biomarkers Immune to Normal Tissue Contamination. Cancer Inform. 2016 Feb 10;15:15-21. PMID: 26884679
  • Fakhry C, Qualliotine JR, Zhang Z, Agrawal N, Gaykalova DA, Bishop JA, Subramaniam RM, Koch WM, Chung CH, Eisele DW, Califano J, Viscidi RP. Serum Antibodies to HPV16 Early Proteins Warrant Investigation as Potential Biomarkers for Risk Stratification and Recurrence of HPV-Associated Oropharyngeal Cancer. Cancer Prev Res (Phila). 2016 Feb;9(2):135-41. PMID: 26701665
  • Guo T, Gaykalova DA, Considine M, Wheelan S, Pallavajjala A, Bishop JA, Westra WH, Ideker T, Koch WM, Khan Z, Fertig EJ, Califano JA. Characterization of functionally active gene fusions in human papillomavirus related oropharyngeal squamous cell carcinoma. Int J Cancer. 2016 March 7th. Int J Cancer. 2016 July 15th; 139 (2): 373-82. Epub 2016 March 30th. PMID: 26949921
  • Fertig EJ, Ozawa H, Thakar M, Howard JD, Kagohara LT, Krigsfeld G, Ranaweera RS, Hughes RM, Perez J, Jones S, Favorov AV, Carey J, Stein-O’Brien G, Gaykalova DA, Ochs MF, Chung CH. CoGAPS matrix factorization algorithm identifies transcriptional changes in AP-2alpha target genes in feedback from therapeutic inhibition of the EGFR network. Oncotarget. 2016 September 16th. [Epub ahead of print]. PMID: 27650546.
  • Stein-O’Brien GL, Carey JL, Lee WS, Considine M, Favorov AV, Flam E, Guo T, Li S, Marchionni L, Sherman T, Sivy S, Gaykalova DA, McKay RD, Ochs MF, Colantuoni C, Fertig EJ. PatternMarkers & GWCoGAPS for novel data-driven biomarkers via whole transcriptome NMF. Bioinformatics. 2017 Feb 8. doi: 10.1093/bioinformatics/btx058. [Epub ahead of print] No abstract available. PMID: 28174896
  • Gaykalova DA*, Zizkova V, Guo T, Tiscareno I, Wei Y, Vatapalli R, Hennessey PT, Ahn J, Danilova L, Khan Z, Bishop JA, Gutkind JS, Koch WM, Westra WH, Fertig EJ, Ochs MF, Califano JA*. Integrative computational analysis of transcriptional and epigenetic alterations implicates DTX1 as a putative tumor suppressor gene in HNSCC. Oncotarget. 2017 Feb 28;8(9):15349-15363. doi: 10.18632/oncotarget.14856. PMID: 28146432. *Corresponding authors (co-senior authors)
  • Makarev E, Schubert A, Kanherkar R, London N, Teka M, Ozerov I, Lezhnina K, Bedi A, Ravi R, Mehra R, Hoque M, Gaykalova DA, Sloma I, Csoka A, Sidransky D, and Zhavoronkov A, Izumchenko E. In silico analysis of pathways activation landscape in oral squamous cell carcinoma and oral leukoplakia. Cell Death Discov. 2017 May 22nd;3:17022. doi: 10.1038/cddiscovery.2017.22. eCollection PMID: 28580171
  • Faraji F, Zaidi M, Fakhry C, Gaykalova DA. Molecular Mechanisms of Human Papillomavirus-Related Carcinogenesis in Head and Neck Cancer. Microbes Infect. 2017 Sep - Oct;19(9-10):464-475. doi: 10.1016/j.micinf.2017.06.001. Epub 2017 June 12th. PMID: 28619685
  • Guo T, Sakai A, Afsari B, Considine M, Danilova L, Favorov AV, Kelley DZ, Flam EL, Khan Z, Wheelan S, Gutkind S, Fertig EJ*, Gaykalova DA*, Califano JA*. Definition of Alternative Splice Expression in HPV-related oropharyngeal cancer includes a novel functional splice variant of AKT3. Cancer Res. 2017 Oct 1;77(19):5248-5258. doi: 10.1158/0008-5472.CAN-16-3106. Epub 2017 July 21st. PMID: 28733453. *Equal contribution
  • Kelley DZ, Flam EL, Izumchenko E, Danilova LV, Wulf HA, Guo T, Singman DA, Bahman A, Skaist A, Considine M, Welch JA, Stavrovskaya E, Bishop JA, Westra WH, Khan Z, Koch WM, Sidransky D, Wheelan S, Favorov AV, Califano JA, Fertig EJ*, Gaykalova DA*. Integrated analysis of whole-genome ChIP-Seq and RNA-Sequencing data of primary head and neck tumor samples associates HPV integration sites with open chromatin marks. Cancer Res. 2017 Dec 1;77(23):6538-6550. doi: 10.1158/0008-5472.CAN-17-0833. Epub 2017 September 25th. PMID: 28947419. *Equal contribution
  • Finegersh A, Kulich S, Guo T, Favorov AV, Fertig EJ, Danilova L, Gaykalova DA, Califano JA, Duvvuri U. DNA methylation regulates TMEM16A/ANO1 expression through multiple CpG islands. Sci Rep. 2017 Nov 9;7(1):15173. doi: 10.1038/s41598-017-15634-9. PMID: 29123240
  • Farhoud Faraji, Adrian D. Schubert, Luciane T. Kagohara, Marietta Tan, Yanxun Xu, Munfarid Zaidi, Jean-Philippe Fortin, Carole Fakhry, Evgeny Izumchenko, Daria A. Gaykalova*, Elana J. Fertig*. Genome-wide molecular landscapes of HPV-positive and HPV-negative head and neck squamous cell carcinoma. Book chapter published in Molecular Determinants of Head and Neck Cancer Series: Current Cancer Research by Springer (editors: Burtness B and Golemis EA). 2018. *Equal Contribution. DOI: 10.1007/978-3-319-78762-6_11
  • Adrian D. Schubert†, Fernando T. Zamuner†, Nyall R. London Jr., Ranee Mehra, Mohammad O Hoque, Elana J. Fertig, David Sidransky, Daria A. Gaykalova*, Evgeny Izumchenko*. Role of NOTCH signaling pathway in Head and Neck Cancer. Book chapter published in Molecular Determinants of Head and Neck Cancer Series: Current Cancer Research by Springer (editors: Burtness B and Golemis EA). 2018. †*Equal Contribution. DOI: 10.1007/978-3-319-78762-6_8
  • Kagohara LT†, Stein-O’Brien G†, Kelley DZ, Flam EL, Wick H, Danilova LV, Easwaran H, Favorov AV, Qian J, Gaykalova DA*, and Fertig EJ*. Epigenetic Regulation of Gene Expression in Cancer: Techniques, Resources, and Analysis. Brief Funct Genomics. 2018 January 1st;17(1):49-63. doi: 10.1093/bfgp/elx018. PMID: 28968850. †*Equal Contribution.
  • Afsari B, Guo T, Considine M, Florea L, Kelley DZ, Flam EL, Ha P, Geman D, Ochs M, Califano JA, Gaykalova DA, Favorov AV, Fertig EJ. Splice Expression Variation Analysis (SEVA) for Differential Gene Isoform Usage in Cancer. Bioinformatics. 2018 Jan 12. doi: 10.1093/bioinformatics/bty004.. PMID: 29342249.
  • Solanki HS, Raja R, Zhavoronkov A, Ozerov IV, Artemov AV, Advani J, Radhakrishnan A, Babu N, Puttamallesh VN, Syed N, Nanjappa V, Subbannayya T, Sahasrabuddhe NA, Patil AH, Prasad TSK, Gaykalova D, Chang X, Sathyendran R, Mathur PP, Rangarajan A, Sidransky D, Pandey A, Izumchenko E, Gowda H, Chatterjee A. Targeting focal adhesion kinase overcomes erlotinib resistance in smoke induced lung cancer by altering phosphorylation of epidermal growth factor receptor. Oncoscience. 2018 Feb 23;5(1-2):21-38.  doi: 10.18632/oncoscience.395. eCollection 2018 Jan. PMID: 29556515
  • Stein-O’Brien G, Kagohara LT, Li S, Thakar M, Ranaweera R, Ozawa H, Cheng H, Considine M, Schmitz S, Favorov AV, Danilova LV, Califano JA, Izumchenko E, Gaykalova DA, Chung CH, Fertig EJ. Integrated time course omics analysis distinguishes immediate therapeutic response from acquired resistance. Genome Med. 2018 May 23rd;10(1):37. doi: 10.1186/s13073-018-0545-2. PMID:  29792227.
  • Rettig EM, Bishop JA, Agrawal N, Chung CH, Sharma R, Zamuner F, Li RJ, Koch WM, Califano JA, Guo T, Gaykalova DA, Fakhry C. HEY1 is expressed independent of NOTCH1 and is associated with poor prognosis in head and neck squamous cell carcinoma. Oral Oncol. 2018 Jul;82:168-175. doi: 10.1016/j.oraloncology.2018.05.017. Epub 2018 June 1st. PMID:  9909892
  • Kelley DZ, Flam EL, Guo T, Danilova LV, Zamuner F, Bohrson C, Considine M, Windsor EJ, Bishop JA, Zhang C, Koch WM, Sidransky D, Westra WH, Chung CH, Califano JA, Wheelan S, Favorov AV, Florea L, Fertig EJ, Gaykalova DA. Functional characterization of alternatively spliced GSN in head and neck squamous cell carcinoma. Transl Res. 2018 July 26th. pii: S1931-5244(18)30108-7. doi: 10.1016/j.trsl.2018.07.007. [Epub ahead of print]. PMID: 30118659
  • Ren S, Gaykalova D, Wang J, Guo T, Danilova L, Favorov A, Fertig E, Bishop J, Khan Z, Flam E, Wysocki PT, DeJong P, Ando M, Liu C, Sakai A, Fukusumi T, Haft S, Sadat S, Califano JA. Discovery and development of differentially methylated regions in human papillomavirus related oropharyngeal squamous cell carcinoma. Int J Cancer. 2018 Aug 2. doi: 10.1002/ijc.31778. [Epub ahead of print]. PMID: 30070359
  • Shaytan AK, Xiao H, Armeev GA, Gaykalova DA, Komarova GA, Wu C, Studitsky VM, Landsman D, Panchenko AR. Structural interpretation of DNA-protein hydroxyl-radical footprinting experiments with high resolution using HYDROID. Nat Protoc. 2018 October 19th. doi: 10.1038/s41596-018-0048-z. [Epub ahead of print]. PMID: 30341436
  • Lopatina T, Favaro E, Grange C, Cedrino M, Ranghino A, Occhipinti S, Fallo S, Buffolo F, GaykalovaDA, Zanone MM, Romagnoli R, Camussi G. PDGF enhances the protective effect of adipose stem cell-derived extracellular vesicles in a model of acute hindlimb ischemia. Sci Rep. 2018 Dec 4;8(1):17458. doi: 10.1038/s41598-018-36143-3. PMID: 30514962
  • Sherman TD, Kagohara LT, Cao R, Cheng R, Satriano M, Considine M, Krigsfeld G, Ranaweera R, Tang Y, Jablonski SA, Stein-O’Brien G, Gaykalova DA, Weiner LM, Chung CH, Fertig EJ. CancerInSilico: An R/Bioconductor package for combining mathematical and statistical modeling to simulate time course bulk and single cell gene expression data in cancer. PLoS Comput Biol. 2019 Apr 19;14(4):e1006935. doi: 10.1371/journal.pcbi.1006935. [Epub ahead of print]. PMID: 31002670
  • Ando M, Saito Y, Xu G, Bui NQ, Medetgul-Ernar K, Pu M, Fisch K, Ren S, Sakai A, Fukusumi T, Liu C, Haft S, Pang J, Mark A, Gaykalova DA, Guo T, Favorov AV, Yegnasubramanian S, Fertig EJ, Ha P, Tamayo P, Yamasoba T, Ideker T, Messer K, Califano JA. Chromatin dysregulation and DNA methylation at transcription start sites associated with transcriptional repression in cancers. Nat Commun. 2019 May 16th;10(1):2188. doi: 10.1038/s41467-019-09937-w. PMID: 31097695
  • Flam EL, Danilova L, Kelley DZ, Stavrovskaya E, Guo T, Considine M, Qian J, Califano JA, Favorov A, Fertig EJ*, Gaykalova DA*. Differentially Methylated Super-Enhancers Regulate Target Gene Expression in Human Cancer. Sci Rep. 2019 Oct 21;9(1):15034. doi: 10.1038/s41598-019-51018-x. PMID: 31636280. *Equal contribution
  • London NR Jr, Rooper LM, Bishop JA, Xu H, Ishii M, Taube JM, Izumchenko E, Gaykalova DA, Gallia GL. Expression of programmed cell death-ligand 1 and associated lymphocyte infiltration in olfactory neuroblastoma. World Neurosurg. 2019 November 27th. pii: S1878-8750(19)32952-3. doi: 10.1016/j.wneu.2019.11.112. [Epub ahead of print]. PMID: 31785431
  • Schubert AD, Channah Broner E, Agrawal N, London N, Pearson A, Gupta A, Wali N, Seiwert TY, Wheelan S, Lingen M, Macleod K, Allen H, Chatterjee A, Vassiliki S, Gaykalova DA, Hoque MO, Sidransky D, Suresh K, Izumchenko E. Somatic mitochondrial mutation discovery using ultra-deep sequencing of the mitochondrial genome reveals spatial tumor heterogeneity in head and neck squamous cell carcinoma. Cancer Lett. 2020 Feb 28;471:49-60. doi: 10.1016/j.canlet.2019.12.006. Epub 2019 December 10th. PMID: 31830557.
  • Guo T, Zambo KDA, Zamuner FT, Ou T, Hopkins C, Kelley DZ, Wulf HA, Winkler E, Erbe R, Danilova L, Considine M, Sidransky D, Favorov A, Florea L, Fertig EJ, Gaykalova DA. Chromatin structure regulates cancer-specific alternative splicing events in primary HPV-related oropharyngeal squamous cell carcinoma. Epigenetics. 2020 March 22nd:1-13. doi: 10.1080/15592294.2020.1741757. [Epub ahead of print]. PMID: 32164487
  • Kagohara LT, Zamuner F, Davis-Marcisak EF, Sharma G, Considine M, Allen J, Yegnasubramanian S, Gaykalova DA*, Fertig EJ*. Integrated single-cell and bulk gene expression and ATAC-seq reveals heterogeneity and early changes in pathways associated with resistance to cetuximab in HNSCC-sensitive cell lines. Br J Cancer. 2020 May 4th. doi: 10.1038/s41416-020-0851-5. [Epub ahead of print]. PMID: 32362655. *Equal contribution
  • Erbe R, Kessler MD, Favorov AV, Easwaran H, Gaykalova DA, Fertig EJ. Matrix factorization and transfer learning uncover regulatory biology across multiple single-cell ATAC-seq data sets. Nucleic Acids Res. 2020 May 11th. pii: gkaa349. doi: 10.1093/nar/gkaa349. [Epub ahead of print]. PMID: 32392348
  • Ren S, Gaykalova DA, Guo T, Favorov AV, Fertig EJ, Tamayo P, Callejas-Valera JL, Allevato M, Gilardi M, Santos J, Fukusumi T, Sakai A, Ando M, Sadat S, Liu C, Xu G, Fisch KM, Wang Z, Molinolo AA, Gutkind JS, Ideker T, Koch WM, Califano JA. HPV E2, E4, E5 drive alternative carcinogenic pathways in HPV positive cancers. Oncogene. 2020 Aug 26. doi: 10.1038/s41388-020-01431-8. Online ahead of print.PMID: 32848210
  • Lopatina T, Favaro E, Danilova L, Fertig EJ, Favorov AV, Kagohara LT, Martone T, Bussolati B, Romagnoli R, Albera R, Pecorari G, Brizzi MF, Camussi G, Gaykalova DA. Extracellular Vesicles Released by Tumor Endothelial Cells Spread Immunosuppressive and Transforming Signals Through Various Recipient Cells. Front Cell Dev Biol. 2020 Sep 9;8:698. doi: 10.3389/fcell.2020.00698. eCollection 2020.PMID: 33015029

Research Interests

The epigenetic landscape of head and neck cancer tissues: In order to demonstrate that head and neck cancer is an epigenetically driven disease, the Gaykalova lab performed chromatin- and DNA methylation-based treatment of HNSCC and salivary adenoid cystic carcinoma samples using JQ1, an inhibitor of the BET family of bromodomain proteins that recognize acetylated lysine residues, as well as azacitidine, an inhibitor of DNA methyltransferases. Strong cellular responses to both of these drugs were observed, supporting the primary hypothesis. To define the functional role of epigenetics in head and neck cancer formation, the team described the whole-genome landscape of chromatin structure and DNA methylation for head and neck samples. They also characterized the role of chromatin and DNA methylation on regulating gene expression of the most potent oncogenes and tumor suppressors and their associated pathways. The newly developed protocol for the whole-genome chromatin analysis of small surgical samples was described in their recent Cancer Research paper. This work showed that the chromatin landscape plays a central role in cancer-specific gene expression profiles and viral genome integration. These scientific directions of the group are summarized in the review “Epigenetic Regulation of Gene Expression in Cancer: Techniques, Resources, and Analysis.” 

Tumor type-specific gene expression profiles of head and neck cancer: Epigenetic and genetic abnormalities regulate disease-specific gene expression changes, which lead to the dysregulation of oncogene and tumor suppressor pathways. To adequately define gene expression profiles, the group performed whole-genome RNA-Seq and array-based analyses of HNSCC tissues. The team determined their tissue type-specific oncogenes and tumor suppressors and their regulating transcription factors. Importantly, this work helped to identify the tumor type-specific alternative splicing profiles of both HPV+ and HPV- HNSCC. Tumor-specific alternatively spliced proteins can potentially be adopted as therapeutic targets, anti-cancer vaccine development targets, or disease biomarkers due to their unique tissue specificity. This research, featured in Cancer Research, Epigenetics, Translational Research, and other papers, defined the role of genetic and epigenetic changes in aberrant gene expression, including alternative splicing events and gene fusions. The group has also participated in the development of new computational methodologies for improved detection of gene expression changes.

The role of transcription factors in head and neck cancer development: In addition to high-throughput head and neck cancer analysis and pathway discovery, the Gaykalova lab is focused on analyzing individual transcription factors, such as STAT1, STAT3, NF-κB, BORIS, TFIIS, FACT, and others. They demonstrated that individual genes are recognized by transcription factors that cause DNA methylation changes, the histone mark landscape, and nucleosome positioning near their transcription start sites to regulate gene expression. Moreover, recent literature suggests that the location of epigenetic enhancer regions and the composition of their associated transcription factors are very tissue-specific. Therefore, knowing the tumor type-specific location of enhancers, it is possible to predict the master transcription factors that regulate tumor type-specific expression. They recently discovered tissue-specific enhancers and their associated transcription factors using modern detection tools. 

The therapeutic venues for HNSCC: There is no effective treatment for HNSCC, as the response rate for the targeted and immune treatment is low, and the recurrence rate is high. The goal of the Gaykalova lab is to fill this scientific knowledge gap and the clinical need. Overall, the team identified multiple therapeutic targets, enabling the further study of their inhibitors. Thus, the epigenetic treatment could be successfully combined with targeted therapeutics to enhance treatment response and to decrease resistance to single-agent therapies. The lab continues efforts on defining the role of chromatin in canonical and alternative gene expression and the role of epigenetic and targeted therapies in the regulation of HNSCC progression. 

Awards and Affiliations

  • Diploma of Honors Degree (Magna Cum Laude), Moscow State University, 2005
  • Conference Travel Award, UMDNJ, 2006, 2008
  • Young Investigator Award, UMDNJ, 2006, 2007, 2008, 2009
  • Financial Aid Award, Genetics Society of America, 2008
  • Best Publication by a Graduate Student, UMDNJ, 2009
  • American Head and Neck Society Pilot Grant Award, AHNS, 2012
  • Head and Neck Cancer Specialized Program of Research Excellence (HNC-SPORE) Pilot Grant Award, NIH, 2014, 2015
  • Head and Neck Cancer Specialized Program of Research Excellence (HNC-SPORE) Career Enhancement Program Core, NIH, 2015
  • R21 Exploratory/Developmental Research Grant Award, NIH/NIDCR, 2015
  • Cervical Cancer Specialized Program of Research Excellence (HNC-SPORE) Career Development Program, NIH, 2017
  • Catalyst Award, Johns Hopkins University, 2018
  • NIH Research Project Grant (Parent R01) “Defining the chromatin structure signature that drives pre-malignant transformation”, NIH/NIDCR, 2019
  • American Cancer Society, Research Scholar, 2021

Grants and Contracts

Active:

05/01/19-04/30/24     NIH R01DE027809 “Delineating Chromatin-Related Gene Expression Signatures as a Function of HNSCC Progression”

09/16/14 – 06/30/20    ECOG 30006561 “CCT 4085-20-EA3161-ECOG-ACRIN-NCI Coop Ga”

Pending:

07/01/21-06/30/25      ACS RSG533967 “Defining the functional role of enhancer-regulation of transcription factors in HPV+ HNSCC” Awarded

Completed:

08/01/18 – 07/31/19   NIH 5P50DE019032 Pilot Project “The discovery of alternative splicing in HPV-related head and neck squamous cell carcinoma”

09/01/17 – 08/31/18   NIH 5P50CA098252 Carrier Development Program “The role of chromatin in tumorigenesis of cervical cancers”

04/01/13-03/31/18      NIH/NCI R01DE023347 Subsite P.I. “Epigenetic Biomarker Discovery in HPV related HNSCC”

07/01/15-06/30/17      NIH/NIDCR R21DE025398 “Characterizing genome-wide alternative splicing in HPV related HNSCC”

08/01/15 – 07/31/17   NIH 5P50DE019032 Pilot Project “The discovery of differentially methylated super-enhancer elements in HPV-related OPSCC”

08/01/14 – 07/31/15   NIH 5P50DE019032 Pilot Project “The discovery of alternative splicing in HPV-related head and neck squamous cell carcinoma”

07/31/12-06/31/13     American Head and Neck Society 241446 “Transcription Factor Signature of Head and Neck Squamous Cell Carcinoma”

 

Professional Activity

National/International Service

Journal editor activities

2020-present      Current Research in Microbial Sciences

Journal peer reviewer activities

2013-present      PloS One Journal

2014-present      Head and Neck Journal

2015-present      International Journal of Cancer

2016-present      Oral Oncology

2016-present      Scientific Reports

2017-present      Clinical Epigenetics

2017-present      Cancer Letters

2019-present      Pharmacology & Therapeutics

2019-present      Bioinformatics

2021-present      Nature Communications

Grant reviewer at study sections

2015                   The Voelcker Fund Grant

2016                   Oral, Dental and Craniofacial Sciences Study Section, NIH, R01/R21

2018                   Million Veteran Program

2018                   DSR, NIDCR Special Grants Review Committee, NIH, F31/K01/R03

2019                   Medical Research Council, U.K.

2020                   NIDCR Special Emphasis Panel ZDE1 Study Section, NIH, R03

2021                   NIDCR R03 Secondary Data Analysis Study Section, NIH, R03

 

Organizational activities

2017, 2019         The Co-chair of the Future of Biomedicine Young Scientist Forum, FEFU, Russia

2018-present      The Course Director of “BioTech 39: Epigenetics”, FAES, NIH, Bethesda, MD

2019                   The Chair of Molecular Medicine Session, FOB International Conference, FEFU, Russia

Advisory committees

2008-2009          The North Jersey Regional Science Fair, Judge

2015-2019          Toby Eagle Foundation, Award Committee member

Local Service       

Grant reviewer

2018                   The STAR Grant for Undergraduate Research, Johns Hopkins University

2019                   The Catalyst Grant, Johns Hopkins University

2019                   The Discovery Grant, Johns Hopkins University

Links of Interest

Previous Positions

  • Research Assistant, Department of Molecular biology, School of Biology, Moscow State University, Moscow, 2003 - 2004 
  • Research Assistant, Department of Pharmacology, UMDNJ - Robert Wood Johnson Medical School, Piscataway, NJ, 2004 - 2005 
  • Ph.D. Student, Department of Pharmacology, UMDNJ - Robert Wood Johnson Medical School, Piscataway, NJ, 2005 - 2009 
  • Postdoctoral Fellow, Johns Hopkins University, Baltimore, MD, 2009 - 2014 
  • Instructor, Johns Hopkins University, Baltimore, MD, 2014 - 2016 
  • Assistant Professor, Johns Hopkins University, Baltimore, MD, 2016 - 2020