About

Sarah E. Millar, Ph.D., is an Emeritus Professor of Dermatology at the University of Pennsylvania School of Medicine. She serves as the Director of the Pilot and Feasibility Grant Program within the Skin Diseases Research Core Center and is a member of the Penn Center of Excellence in Environmental Toxicology. Dr. Millar is also the Co-Director of the Institute for Regenerative Medicine Program in Epithelial Stem Cells and Regeneration and holds memberships in the Institute for Diabetes, Obesity and Metabolism, as well as the Penn Diabetes Research Center. She is actively involved in the Office of Inclusion and Diversity Advisory Council at the Perelman School of Medicine and has held the position of Vice Chair for Basic Research in the Department of Dermatology. Her research focuses on understanding cell-cell signaling mechanisms that control development, stem cell function, and regeneration of the epidermis and organs such as hair follicles, mammary glands, taste papillae, and teeth that arise from embryonic ectoderm. Dr. Millar's work has demonstrated the essential role of Wnt/beta-catenin signaling in initiating the formation of ectodermal appendages and regulating adult epithelial stem cell functions. Her investigations include using genetic approaches to elucidate how Wnt signaling is regulated and patterned within the skin, as well as exploring epigenetic mechanisms, such as the functions of histone deacetylases, in skin development, differentiation, regeneration, and tumorigenesis. She has contributed to the understanding of skin and hair follicle tumorigenesis, skin epigenetics, and the development of hair follicles, mammary glands, and teeth, with a particular emphasis on stem cell biology and signaling pathways.

Research topics

• Medicine
• Internal medicine
• Surgery
• Virology
• Cancer research
• Immunology
• Emergency medicine
• Biology
• Genetics
• Intensive care medicine
• Cell biology
• Environmental health

Selected publications

• 0882 Patterning and regional specification of hairy skin

  Journal of Investigative Dermatology · 2025-07-21

  articleOpen accessSenior author
  PublisherOA PDFDOI

• KRT6A and KRT17 mark distinct stem cell populations in the adult palpebral conjunctiva and Meibomian gland

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-11 · 1 citations

  preprintOpen accessSenior author

  Abstract Purpose To investigate whether KRT6A or KRT17 label self-renewing stem cells (SCs) in adult Meibomian gland (MG) and palpebral conjunctiva (PC) homeostasis and explore the mechanisms that regulate their expression in these tissues. Methods KRT6A and KRT17 expression in adult mouse MG and PC was examined by single nucleus RNA sequencing and immunofluorescence (IF). Bromodeoxyuridine pulse-chase assays were conducted to assess the turnover rate of PC progenitor cells. Lineage tracing experiments were performed using Krt6a-Cre ERT2 and Krt17-Cre ERT2 mice carrying Rosa26R nTnG or Rosa26R mTmG reporter. As Hedgehog (Hh) signaling, the histone deacetylase HDAC3, and the transcription factor KLF4, regulate KRT6A and KRT17 in other contexts, IF was conducted to assess the in vivo effects of overexpression of the Hh pathway activator GLI2ΔN, and inducible epithelial deletion of Hdac3 or Klf4 , on KRT6A and KRT17 expression in the MG and PC. Results KRT6A and KRT17 are primarily expressed in the MG central duct and ductules. KRT6A also shows robust expression in PC. MG and PC epithelial progenitor cells turn over within 14 days. Lineage tracing indicated that Krt17 labels self-renewing SCs in the MG whereas Krt6a labels SCs in the PC. GLI2ΔN overexpression induced ectopic KRT17 expression in MG acini and PC but did not affect KRT6A expression in either MG or PC. Hdac3 deficiency caused expanded expression of KRT6A and KRT17 in MG acini and ectopic KRT17 expression in PC. Klf4 deletion resulted in ectopic KRT17 expression in PC but did not influence KRT6A expression in MG or PC. Conclusions Krt6a - and Krt17 -expressing cells contribute to adult PC and MG homeostasis, respectively. KRT17 expression is enhanced by GLI2ΔN, and suppressed by HDAC3 and KLF4, whereas KRT6A expression is controlled only by HDAC3.

  PublisherDOI

• Identification of Meibomian gland stem cell populations and mechanisms of aging

  Nature Communications · 2025-02-15 · 17 citations

  articleOpen accessSenior author

  Meibomian glands secrete lipid-rich meibum, which prevents tear evaporation. Aging-related Meibomian gland shrinkage may result in part from stem cell exhaustion and is associated with evaporative dry eye disease, a common condition lacking effective treatment. The identities and niche of Meibomian gland stem cells and the signals controlling their activity are poorly defined. Using snRNA-seq, in vivo lineage tracing, ex vivo live imaging, and genetic studies in mice, we identify markers for stem cell populations that maintain distinct regions of the gland and uncover Hedgehog (Hh) signaling as a key regulator of stem cell proliferation. Consistent with this, we show that human Meibomian gland carcinoma exhibits increased Hh signaling. Aged glands display decreased Hh and EGF signaling, deficient innervation, and loss of collagen I in niche fibroblasts, indicating that alterations in both glandular epithelial cells and their surrounding microenvironment contribute to age-related degeneration. These findings suggest new approaches to treat aging-associated Meibomian gland loss.

  PublisherOA PDFDOI

• Nuclear force transmission drives cancer-associated fibroblast activation under BRAF inhibition

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-23 · 1 citations

  preprintOpen access

  Cancer-associated fibroblasts (CAFs) exhibit striking plasticity, enabling them to adapt to external cues such as therapeutic and mechanical stress in the tumor microenvironment (TME). Here, we uncover a shared mechanotransduction pathway through which both BRAF inhibition and matrix stiffness converge in nuclear remodeling to drive CAF activation. Mechanistically, BRAF inhibitors (BRAFis) accelerate RAS-dependent RAF homo and heterodimerization and ERK signaling, leading to GSK-3β inactivation and Rho kinase (ROCK) activation. In parallel, stiff substrates engage integrin receptors to directly activate ROCK signaling. Activation of ROCK induces actin stress fiber assembly, generating mechanical forces that deform the nucleus. In both contexts, nuclear reshaping promotes β-catenin translocation and actin polymerization through a feedback loop that continuously enforces CAF activation and promotes melanoma progression. Notably, pharmacological inhibition of ROCK activity blocks both BRAFi- and stiffness-induced nuclear remodeling and β-catenin accumulation, identifying the ROCK-cytoskeleton-nucleus axis as a critical regulator of CAF adaptation and functionality. Collectively, these findings reveal a mechanically tuned nuclear signaling hub that integrates chemical and physical cues to promote stromal adaptation and suggest ROCK inhibition as a strategy to counteract therapy-induced fibroblast reprogramming and improve therapy response.

  PublisherOA PDFDOI

• Identification of Meibomian gland stem cell populations and mechanisms of aging

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-08-10 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Meibomian glands secrete lipid-rich meibum, which prevents tear evaporation. Aging-related Meibomian gland shrinkage may result in part from stem cell exhaustion and is associated with evaporative dry eye disease, a common condition lacking effective treatment. The identities and niche of Meibomian gland stem cells and the signals controlling their activity are poorly defined. Using snRNA-seq, in vivo lineage tracing, ex vivo live imaging, and genetic studies in mice, we identified markers for stem cell populations that maintain distinct regions of the gland and uncovered Hh signaling as a key regulator of stem cell proliferation. Consistent with this, human Meibomian gland carcinoma exhibited increased Hh signaling. Aged glands displayed decreased Hh and EGF signaling, deficient innervation, and loss of collagen I in niche fibroblasts, indicating that alterations in both glandular epithelial cells and their surrounding microenvironment contribute to age-related degeneration. These findings suggest new approaches to treat aging-associated Meibomian gland loss.

  PublisherOA PDFDOI

• HDAC1/2 and HDAC3 play distinct roles in controlling adult Meibomian gland homeostasis

  The Ocular Surface · 2024-04-26 · 7 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• HDAC1/2 and HDAC3 play distinct roles in controlling adult Meibomian gland homeostasis

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-02-07 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Purpose To investigate the roles of HDAC1/2 and HDAC3 in adult Meibomian gland (MG) homeostasis. Methods HDAC1/2 or HDAC3 were inducibly deleted in MG epithelial cells of adult mice. The morphology of MG was examined. Proliferation, apoptosis, and expression of MG acinus and duct marker genes, meibocyte differentiation genes, and HDAC target genes, were analyzed via immunofluorescence, TUNEL assay, and RNA in situ hybridization. Results Co-deletion of HDAC1/2 in MG epithelium caused gradual loss of acini and formation of cyst-like structures in the central duct. These phenotypes required homozygous deletion of both HDAC1 and HDAC2, indicating that they function redundantly in the adult MG. Short-term deletion of HDAC1/2 in MG epithelium had little effect on meibocyte maturation but caused decreased proliferation of acinar basal cells, excessive DNA damage, ectopic apoptosis, and increased p53 acetylation and p16 expression in the MG. By contrast, HDAC3 deletion in MG epithelium caused dilation of central duct, atrophy of acini, defective meibocyte maturation, increased acinar basal cell proliferation, and ectopic apoptosis and DNA damage. Levels of p53 acetylation and p21 expression were elevated in HDAC3-deficient MGs, while the expression of the differentiation regulator PPARγ and the differentiation markers PLIN2 and FASN was downregulated. Conclusions HDAC1 and HDAC2 function redundantly in adult Meibomian gland epithelial progenitor cells and are essential for their proliferation and survival, but not for acinar differentiation, while HDAC3 is required to limit acinar progenitor cell proliferation and permit differentiation. HDAC1/2 and HDAC3 have partially overlapping roles in maintaining survival of MG cells.

  PublisherOA PDFDOI

• Supplementary Figure 3 from Canonical Wnt Signaling Is Required for Pancreatic Carcinogenesis

  2023-03-30

  preprintOpen access

  <p>PDF file - 879K, Supplemental Figure 3. PAS, Gomori Trichrome and Claudin18 IHC staining in KC and KDC pancreas.</p>

  PublisherOA PDFDOI

• Supplementary Figure 3 from Canonical Wnt Signaling Is Required for Pancreatic Carcinogenesis

  2023-03-30

  preprintOpen access

  <p>PDF file - 879K, Supplemental Figure 3. PAS, Gomori Trichrome and Claudin18 IHC staining in KC and KDC pancreas.</p>

  PublisherDOI

• Supplementary Figure 2 from Canonical Wnt Signaling Is Required for Pancreatic Carcinogenesis

  2023-03-30

  preprintOpen access

  <p>PDF file - 6297K, Supplemental Figure 2. Pancreatic histology in DKK1 mice on doxy; KC and KDC mice without doxy.</p>

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01AR063146

  NIH · $1.7M · 2019

• Cutaneous Phenomics and Transcriptomics

  NIH · $16.0M · 2016–2026

• NIH Grant RC1DE020337

  NIH · $800k · 2012

• Penn Dermatology Research Training Program

  NIH · $9.9M · 1983–2029

• NIH Grant R56DE023100

  NIH · $400k · 2016

Frequent coauthors

• Simrandeep Singh

  Guru Gobind Singh Medical College and Hospital

  107 shared

• Marylise Boutros

  Cleveland Clinic Florida

  85 shared

• Lorenzo Conti

  University of Pisa

  83 shared

• Sudha Sundar

  University of Birmingham

  83 shared

• Ana Minaya‐Bravo

  Instituto Cajal

  81 shared

• H Salem

  76 shared

• Sana Ali

  Allama Iqbal Open University

  75 shared

• Raghavan Vidya

  The Royal Wolverhampton NHS Trust

  67 shared

Labs

• Sarah E. Millar LabPI

Awards & honors

• Member, Penn Center of Excellence in Environmental Toxicolog…
• Chair, Penn Medicine Child Care Task Force, University of Pe…
• Co-Director, Institute for Regenerative Medicine Program in…