Andrey A. Sharov, MD, PhD

Assistant Professor of Dermatology

Summary

Based on functional activities, the eukaryotic genome consists of two major chromatin types: transcriptionally silent heterochromatin and transcriptionally active euchromatin. A major function of heterochromatin is to protect the underlying DNA from being accessed by dedicated machineries, thus preventing its use for transcription or other DNA-based transactions. Our research focuses on the molecular mechanisms of heterochromatin formation, maintenance, and remodeling during epidermal development, growth, wound healing, and aging. We study multiple epigenetic mechanisms such as DNA methylation, covalent histone modifications, chromatin remodeling proteins, and 3D-chromatin interactions, all of which are crucial for precise gene expression during cellular differentiation. These regulatory mechanisms become gradually deregulated during aging, compromising cellular functions.

Specifically, sequences embedded in heterochromatin often contain repetitive elements, such as transposable elements (transposons). Currently, we‘re investigating the role of transposable elements in epidermal development, homeostasis, and keratinocyte differentiation. This project addresses key questions regarding the regulation of transposable elements in normal keratinocytes, the mechanisms that control their silencing, and the consequences of compromised silencing on epidermal development and homeostasis.

Another aspect of our research examines the differences in the expression of genome transposable elements between epidermal keratinocytes isolated from the skin of African American, Hispanic, Asian, and non-Hispanic White individuals. This study aims to understand the mechanisms regulating transposable element silencing in keratinocytes of different ethnic backgrounds and to explore whether modulation of inflammatory response by nucleoside reverse transcriptase inhibitors might serve as a new approach for managing skin inflammatory conditions in individuals with understudied skin types.

The findings from these research projects are expected to facilitate the development of novel therapeutic interventions for skin inflammatory conditions and their prevention, particularly in patients with skin of color. Our studies are supported by grants from the NIH/NIAMS.

Research Interests

  • Skin Development
  • Hair Cycling
  • Epigenetics
  • Epithelial Stem Cells
  • Pigmentation
  • Melanoma
  • Epithelization and keratinization
  • Wound Healing
  • Aging


Selected Publications

  1. Kida M, Fatima I, Rozhkova E, Otero-Viñas M, Wu M, Kalin JH, Cole PA, Falanga V, Alani RM, Sharov AA. Inhibition of the CoREST Repressor Complex Promotes Wound Re-Epithelialization through the Regulation of Keratinocyte Migration. J Invest Dermatol. 2024 Feb;144(2):378-386.e2. PMID: 37633457
  2. Chen GD, Fatima I, Xu Q, Rozhkova E, Fessing MY, Mardaryev AN, Sharov AA, Xu GL, Botchkarev VA. DNA dioxygenases Tet2/3 regulate gene promoter accessibility and chromatin topology in lineage-specific loci to control epithelial differentiation. Sci Adv. 2023 Jan 13;9(2): PMID: 36630508; PubMed Central PMCID: PMC9833667
  3. Fatima I, Chen G, Botchkareva N, Sharov A, Thornton D, Wilkinson HN, Hardman MJ, Grutzkau A, Pedrode Magalhaes J, Seluanov A, Smith EJ, Gorbunova V, Mardaryev AN, Faulkes CG, Botchkarev VA. Skin aging in long-lived naked mole rats is accompanied by increased expression of the longevity-associated and tumor suppressor genes. J Invest Dermatol. 2022;142(11):2853-2863.e4 PMID: 35691364
  4. Sharova TY, Poterlowicz K, Botchkareva NV, Kondratiev NA, Aziz A, Spiegel JH, Botchkarev VA, Sharov AA. Complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy. J Invest Dermatol. 2014, 134, 2873-82. PMID: 24999588
  5. Lewis CJ, Mardaryev AN, Poterlowicz K, Sharova TY, Aziz A, Sharpe DT, Botchkareva NV, Sharov AA. Bone morphogenetic protein signaling suppresses wound-induced skin repair by inhibiting keratinocyte proliferation and migration. J Invest Dermatol. 2014 Mar;134(3):827-37. PMID: 24126843 ; PMCID: PMC 3945401
  6. Sharov AA, Fessing MY, Atoyan R, Sharova TY, Haskell-Luevano C, Weiner L, Funa K, Brissette JL, Gilchrest BA, Botchkarev VA. Bone morphogenetic protein (BMP) signaling controls hair pigmentation by means of cross-talk with the melanocortin receptor-1 pathway. Proc Natl Acad Sci USA, 2005, 102, 93-98. PMID: 15618398.

    7. Sharov AA, SharovaTY, Mardariev AN, Tommasi di Vignano A, Atoyan R, Weiner L, Yang S, Brissette JL, Dotto GP, Botchkarev VA. BMP signaling controls hair follicle size and modulates the expression of cell cycle-associated genes. Proc Natl Acad Sci USA, 2006, 103, 18166-18171. PMID: 17114283

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