About

John T. Seykora, M.D., Ph.D., is a Professor of Dermatology at the University of Pennsylvania's Perelman School of Medicine and a member of the Abramson Cancer Center at the Hospital of the University of Pennsylvania. His research expertise includes keratinocyte growth and differentiation, mechanisms of growth control, skin cancer such as squamous cell carcinoma, SCCIS, and actinic keratoses, as well as signal transduction involving tyrosine kinases and adaptor molecules. He utilizes murine models of human diseases and organotypic cultures to model disease processes, with particular focus on the effects of UVB on keratinocytes, psoriasis, and dermatopathology related to alopecia, appendageal tumors, and cancer. Dr. Seykora's clinical expertise encompasses dermatopathology, including analysis of alopecias, appendageal neoplasms, melanocytic lesions, and molecular analysis of biopsy tissue. His educational background includes a B.A. and M.S. in Biology and Biochemistry from the University of Chicago, a Ph.D. in Cell Biology from Rockefeller University, and an M.D. from Cornell University Medical College. His contributions to the field are reflected in his research on skin biology, cancer mechanisms, and innovative modeling of dermatological diseases.

Research topics

• Medicine
• Immunology
• Pathology
• Internal medicine
• Cancer research
• Biology
• Genetics
• Oncology
• Cell biology

Selected publications

• Author Correction: Leveraging deep single-soma RNA sequencing to explore the neural basis of human somatosensation

  Nature Neuroscience · 2026-03-06

  articleOpen access

  In the version of this article initially published, several figure elements were incorrect.In Fig. 4c, the labels "hPEP.PIEZo h ", "hAb.LTMR", and "hAd.LTMR" should have read "hPEP.PIEZO h ", "hA.LTMR", and "hA.LTMR", respectively.In Fig. 4d, the positions of the x-axis labels "CHRNA7" and "KIT" were swapped.In Fig. 4e, the panels for "hPEP.NTRK3" and "hA.LTMR" inadvertently showed the same image; the "hA.LTMR" panel has been replaced with the correct image.In Fig. 8i, the label "C-HTMR Heat + " should be "C-HTMR Cool + ."Also, in Fig. 8i, the axis tick label "20" was a typographical concatenation and should appear as two separate ticks, "2" and "0."In Fig. 8i-j, the label "noxious range" has been removed; the grey shading is intended only to indicate the sustained phase (already denoted by "0 C sustained" and "50 C sustained").These errors have

  PublisherOA PDFDOI

• Inhibiting LSD1 unlocks retinoid AP-1 programming to activate epithelial immunity and skin tumor suppression

  Journal of Clinical Investigation · 2026-03-12

  articleOpen access

  Lysine-specific demethylase 1 (LSD1; KDM1A) orchestrates context-dependent chromatin programs, yet its role in epithelial immunity remains largely unknown. Here, we identify LSD1 as a central brake on retinoid-driven and activator protein-1-driven (AP-1-driven) enhancer activation in epidermis and demonstrate that its inhibition induces antitumor immunity. Whereas epidermal LSD1 is required during development, acute loss or topical inhibition in adult skin was tolerated and triggered coordinated expression of retinoic acid signaling, lipid remodeling, and chemokine induction pathways. CUT&RUN profiling revealed that LSD1 occupies enhancer regions enriched for AP-1 motifs at retinoid metabolism, lipid homeostasis, and immune genes. LSD1 loss increased H3K4me1/2 and gene activation at these sites, licensing a poised AP-1-retinoid program. Single-cell spatial analyses showed that discrete keratinocyte subsets initiate retinoid signaling to recruit dendritic cells and activate CD4+ T cell responses. Topical LSD1 inhibition suppressed cutaneous squamous cell carcinoma in 2 models while amplifying keratinocyte-immune cell crosstalk. Functional perturbations revealed that retinoid signaling partially contributes to, whereas CD4+ T cells are essential for, tumor control. These findings define LSD1 as a master repressor of epithelial immune competence and nominate LSD1 inhibition as a therapeutic strategy to activate retinoid-AP-1 enhancer circuits and drive CD4-dependent tumor immunity in skin cancer.

  PublisherOA PDFDOI

• Figure 5 from LNS8801: An Enantiomerically Pure Agonist of the G Protein–Coupled Estrogen Receptor Suitable for Clinical Development

  2025-04-04

  preprintOpen access

  <p>GPER staining in normal tissues. <b>A,</b> Representative images of GPER-positive staining areas in normal tissues, scale bar, 50 μm. <b>B,</b> Percentage of noncancerous tissue samples with GPER staining across normal tissues; epithelial tissues were quantitated with staining in the epithelial region of the tissue specifically, and denoted with (epi). WT, wildtype.</p>

  PublisherDOI

• Supplemental Figure 2 from LNS8801: An Enantiomerically Pure Agonist of the G Protein–Coupled Estrogen Receptor Suitable for Clinical Development

  2025-05-13

  preprintOpen access

  <p>S2. LNS8801 is active in the WM46 human xenograft model.</p>

  PublisherDOI

• Three types of alopecia in one patient: A case of central centrifugal cicatricial alopecia, alopecia areata, and telogen effluvium

  JAAD Case Reports · 2025-07-01

  articleOpen access
  PublisherDOI

• Supplemental Figure 1 from LNS8801: An Enantiomerically Pure Agonist of the G Protein–Coupled Estrogen Receptor Suitable for Clinical Development

  2025-04-04

  preprintOpen access

  <p>S1. Validation of LNS8801 activity and necessity of GPER in HL-60 cells.</p>

  PublisherDOI

• Figure 4 from LNS8801: An Enantiomerically Pure Agonist of the G Protein–Coupled Estrogen Receptor Suitable for Clinical Development

  2025-04-04

  preprintOpen access

  <p>GPER is necessary, and genetic variation affects LNS8801 effects. <b>A,</b> Western blot demonstrating CRISPR-Cas9 GPER depletion and LNS8801 dose-response proliferation assay in YUMM1.7 cells (melanoma), <i>n</i> = 6 replicates per dose. <b>B,</b> Western blot demonstrating CRISPR-Cas9 GPER depletion and LNS8801 dose-response proliferation assay in 2838c3 cells (pancreatic cancer), <i>n</i> = 6 replicates per dose. <b>C,</b> Tumor volumes and (<b>D</b>) Kaplan–Meier survival curves measured over time in YUMM1.7 melanoma–bearing mice with GPER (GPER WT) and without GPER (GPER KO) treated with orally delivered vehicle or LNS8801 at 1 mg/kg, significance by log-rank (Mantel–Cox). To control for tumor size, treatment was started when tumor sizes were equal; day 7 and day 27 after tumor injection for GPER WT and GPER KO tumor-bearing mice, respectively. Additional statistical information for <b>F</b> is presented in Supplementary Table S2. <b>E,</b> CREB reporter assay of human melanocytes with CRISPR-Cas9 depleted GPER treated with LNS8801, significance by the Mann–Whitney test. <b>F,</b> CREB reporter assay of human melanocytes homozygous for consensus germline GPER (C/C) and heterozygous for variant germline GPER (C/V) treated with 50 nmol/L LNS8801, significance by the Mann–Whitney test.</p>

  PublisherDOI

• Supplemental Table 2 from LNS8801: An Enantiomerically Pure Agonist of the G Protein–Coupled Estrogen Receptor Suitable for Clinical Development

  2025-05-13

  preprintOpen access

  <p>Log-rank (Mantel-Cox) all comparisions of data in Figure 2 and 4.</p>

  PublisherDOI

• Supplemental Table 1 from LNS8801: An Enantiomerically Pure Agonist of the G Protein–Coupled Estrogen Receptor Suitable for Clinical Development

  2025-05-13

  preprintOpen access

  <p>Off-target binding of LNS8801 and LNS8812 using Eurofins Discover X.</p>

  PublisherDOI

• Figure 1 from LNS8801: An Enantiomerically Pure Agonist of the G Protein–Coupled Estrogen Receptor Suitable for Clinical Development

  2025-04-04

  preprintOpen access

  <p>G-1 is a racemic compound. <b>A,</b> Chemical structures of the enantiomers of racemic G-1, LNS8801, and LNS8812. <b>B,</b> Proliferation of YUMM1.7 melanoma cells treated with 500 nmol/L G-1, LNS8801, or LNS8812. <i>n</i> = 5 per group, * denotes significance by one-way ANOVA, α = 0.05. <b>C,</b> Proliferation of 2838c3 PDAC cells treated with 500 nmol/L G-1, LNS8801, or LNS8812. <i>n</i> = 5 per group, * denotes significance by one-way ANOVA, α = 0.05. The dotted line indicates the number of cells in each well at the start of the 4-day incubation.</p>

  PublisherDOI

Recent grants

• Cutaneous Phenomics and Transcriptomics

  NIH · $16.0M · 2016–2026

• The role of Fyn and Srcasm in UVB-induced cutaneous neoplasia

  NIH · $1.6M · 2012–2018

• NIH Grant K08AR047597

  NIH · $624k · 2007

• Mechanisms regulating the early stages of UV-induced skin cancer

  NIH · $1.8M · 2018–2024

• NIH Grant R01AR051380

  NIH · $1.6M · 2011

Frequent coauthors

• Weijie Li

  Fujian Institute of Oceanography

  60 shared

• Aimee Payne

  University of Pennsylvania

  52 shared

• Warren R. Heymann

  Cooper Medical School of Rowan University

  50 shared

• Jeanette Camacho

  49 shared

• Bruce Pawel

  49 shared

• Albert C. Yan

  Children's Hospital of Philadelphia

  49 shared

• Rhonda E. Schnur

  Cooper Medical School of Rowan University

  49 shared

• Paul J. Honig

  University of Pennsylvania

  49 shared

Labs

• John T. Seykora LaboratoryPI