Daria A. Gaykalova, PhD

Complete List of Published Work in My Bibliography:
https://www.ncbi.nlm.nih.gov/myncbi/daria.gaykalova.1/bibliography/public/

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. 

• 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

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”

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

https://www.igs.umaryland.edu/

• 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