Black Family Stem Cell Institute

Skin, Hair and Oral Stem Cells

Skin and the oral epithelium of the mouth are intricate structures composed of the outer keratinized epidermis and the underlying dermal connective tissue.

Together, they act as the first defensive barrier against harmful external agents. Therefore, it is crucial to maintain homeostasis, replenish, and—if wounded—repair any break in the skin. All of these processes rely heavily not only on the regenerative capacity of several stem cell populations in the skin and its appendages, and the mouth epithelium, but also on their interaction with surrounding dermal tissue. Aberration in the balance between maintenance and regeneration can cause several types of skin disease.

The adult hair follicle, one of the epidermal appendages, is a remarkable model to study how epidermis-derived stem cells contribute to hair regeneration in a cyclical fashion and how the dermal counterpart, the dermal papilla, regulates its functions. Understanding these processes will help us develop new skin and hair regenerative therapies. Investigators at the Black Family Stem Cell Institute work to uncover the key regulatory molecular events that maintain these delicate homeostatic and regenerative processes in the various adult skin compartments.

Investigators with a major focus in skin, hair, and oral stem cell research include:

Julio Aguirre-Ghiso

Julio Aguirre-Ghiso, PhD, is a Professor at the Icahn School of Medicine at Mount Sinai in the Division of Hematology and Oncology in the Departments of Medicine, Otolaryngology, and Oncological Sciences; the Research Leader of the Metastasis Treatment Center and Co-leader of the Cancer Mechanisms Program at The Tisch Cancer Institute, an NCI-designated center, and Director of Head and Neck Cancer Basic Research in the Department of Otolaryngology. He focuses on one of the major challenges faced by physicians: prevention and treatment of metastasis, which is the main reason for cancer mortality. Cancer patients presumed cured after primary tumor removal and therapy can carry non-proliferating ‘dormant’ disseminated tumor cells (DTCs) for years before reactivating to form incurable metastasis. Dr. Aguirre-Ghiso’s work focuses on understanding the biology of residual cancer cells that persist in a dormant state after initial therapy. His team led a paradigm shift revealing novel cancer biology that diverges from the notion that cancer is perpetually proliferating. They discovered that reciprocal crosstalk between DTCs and the microenvironment regulates the inter-conversion between dormancy and proliferation. This knowledge will allow targeting minimal residual disease before it becomes clinically detectable, and thus preventing recurrences.

Ongoing research interests include:

  • Exploring mechanisms controlling residual cancer dormancy
  • Researching approaches to target dormant cancer cells
  • Identifying markers to determine whether disseminated disease cells are dormant or active

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Elena Ezhkova, PhD

Elena Ezhkova, PhD, is an Associate Professor in the Cell, Developmental, and Regenerative Biology Department. Her laboratory implements an array of powerful cellular and high-throughput molecular biology tools to dissect how epigenetic gene regulators, specifically the polycomb repressive complexes 1 and 2 (PRC1 and PRC2), play a role in cell fate determination, homeostasis, and regeneration. Her lab has recently showed that PRC1 functions both as a transcriptional repressor and as a transcriptional activator during skin development. Importantly, PRC1-mediated gene activating functions are critical for hair follicle development and for the establishment of the adult bulge stem cell compartment. Identification of these molecular mechanisms that control cell fate determination, commitment, and differentiation aids in expanding our understanding of tissue development and the progression of various tissue disorders, including cancer. 

Ongoing research interests include:

  • Uncovering the molecular mechanism of PRC-mediated gene regulation in skin development, homeostasis, and regeneration
  • Dissecting the canonical and non-canonical PRC function in different epithelial tissues, including skin and oral epithelia
  • Uncovering the molecular mechanisms controlling Merkel cell development and maintenance and Merkel cell carcinoma formation

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Sarah E. Millar

Sarah E. Millar, PhD, is Director of the Black Family Stem Cell Institute, and Lillian and Henry M. Stratton Professorial Chair in the Departments of Cell, Developmental, and Regenerative Biology, and Dermatology at the Icahn School of Medicine at Mount Sinai. Understanding the molecular and cellular mechanisms regulating the development, patterning, and postnatal renewal of the skin and ectodermal appendage organs such as hair follicles, teeth, and taste papillae, and identifying stem and progenitor cell populations in these organs, is critical for developing new therapies to accelerate wound healing, treat hair loss diseases, repair or replace diseased teeth, and ameliorate taste dysfunction. Research in the Millar Laboratory focuses on cell-cell signaling and epigenetic mechanisms that underlie these processes. In published research, researchers identified Wnt/beta-catenin signaling as a key pathway required for initiating the formation of ectodermal appendages from multipotent cells in mammalian embryos, and in controlling development and patterning of haired versus hairy skin. By analyzing genetic mouse models and tissues from human patients carrying mutations in the WNT10A gene, we showed that Wnt signaling plays a key role in regulating the functions of a wide variety of adult epithelial stem cells, as well as in controlling specialized differentiation programs in palmoplantar skin. We have also identified critical functions for epigenetic regulators including micro-RNAs and chromatin modifiers in skin development and regeneration.

Ongoing research interests include:

  • Investigating mechanisms that cause ectodermal dysplasia in patients with mutations in the WNT10A gene, and testing potential therapeutic strategies
  • Determining the mechanisms that underlie the formation and maintenance of hairy versus hairless skin and regulate hair patterning
  • Delineating the functions of histone deacetylase chromatin modifiers in skin development, stem cells, and cancer
  • Identifying pioneer transcription factors that control development and stem cell activity in skin and oral epithelia

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Michael Rendl

Michael Rendl, MD, is a Professor of Cell, Developmental, and Regenerative Biology and Dermatology at the Icahn School of Medicine at Mount Sinai; Director of the NYSTEM Training Program in Stem Cell Biology; and Associate Director of the Black Family Stem Cell Institute. His team studies the formation and function of stem cell niches, using hair follicle formation during skin development and adult hair growth and regeneration as a model system. Dermal papilla (DP) cells are specialized mesenchymal niche cells that instruct hair follicle stem cells and progenitors. His laboratory discovered embryonic DP precursors, defined molecular signatures of embryonic and mature DP cells, and established the essential roles of Wnt signaling and the transcription factor Sox2 for DP functions. The lab has uncovered the DP-related dermal sheath (DS) as a key niche component for hair cycle progression and progenitor pruning, essential for the next wave of stem cell activation. Overall, insights from these studies reveal mechanisms on how stem cell niches function and provide a platform for developing hair regenerative therapies.

Ongoing research interests include:

  • Understanding the molecular controls that regulate DP niche fate and function
  • Investigating DP signals that regulate stem cell and progenitor functions
  • Dissecting DS cellular and molecular mechanisms of hair cycle regulation

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