Faculty Bibliography

Squamous cell carcinoma (SCC) growth is governed by tumor propagating progenitor cells (TPCs) that self-renew and differentiate into SCC cells without proliferative potential. The molecular mechanisms controlling this fate choice within these tumors are still elusive. Here we identify PITX1 as a fate determining transcription factor in mouse and human SCCs. PITX1 co-localizes with SOX2 and TRP63 in nuclei of TPCs, but it is not detected in differentiated SCC cells. Conditional gene targeting combined with ChIP-sequencing and transcriptomics reveals PITX1 cooperates with SOX2 and TRP63 to sustain a SCC specific transcriptional feed forward circuit that maintain TPC-renewal, while they also inhibit Klf4transcription and KLF4 dependent squamous differentiation. Conversely, KLF4 represses PITX1, SOX2 and TRP63 expression to prevent their expansion into supra-basal layers. This bi-stable multi-input network motif provides a molecular framework that explains self-renewal, aberrant differentiation and SCC growth in mice and humans, revealing new clues for differentiation stimulating therapies for SCCs.

Basal tumor propagating cells (TPCs) control squamous cell carcinoma (SCC) growth by self-renewing and differentiating into supra-basal SCC cells, which lack proliferative potential. While transcription factors such as SOX2 and KLF4 can drive these behaviors, their molecular roles and regulatory interactions with each other have remained elusive. Here, we show that PITX1 is specifically expressed in TPCs, where it co-localizes with SOX2 and TRP63 and determines cell fate in mouse and human SCC. Combining gene targeting with chromatin immunoprecipitation sequencing (ChIP-seq) and transcriptomic analyses reveals that PITX1 cooperates with SOX2 and TRP63 to sustain an SCC-specific transcriptional feed-forward circuit that maintains TPC-renewal, while inhibiting KLF4 expression and preventing KLF4-dependent differentiation. Conversely, KLF4 represses PITX1, SOX2, and TRP63 expression to prevent TPC expansion. This bi-stable, multi-input network reveals a molecular framework that explains self-renewal, aberrant differentiation, and SCC growth in mice and humans, providing clues for developing differentiation-inducing therapeutic strategies.

Lichen planus pigmentosus (LPP) is an uncommon variant of lichen planus of unclear etiology that predominantly affects patients of skin types III to VI. We report a case of LPP of two years duration in a 67-year-old man involving upper extremities, chest, abdomen, and upper back.

Folliculotropic mycosis fungoides (MF) is a distinct subset of cutaneous T cell lymphoma (CTCL). The disease is typically marked by an aggressive course and is often recalcitrant to skin-direct therapy. We report a case of an 83-year-old woman with folliculotropic MF characterized by erythematous, scaly plaques on the forehead along with poliosis and alopecia of the right medial eyebrow.

We present a case of necrobiosis lipoidica (NL) of the right abdomen in a 75-year-old man. A skin biopsy performed showed a layered infiltrate of mono and multinucleated histiocytes palisaded around degenerated collagen bundles. Laboratory workup was unremarkable. The patient was treated with topical corticosteroids with cessation of progression of his disease, although the eruption did not resolve. There are a number of treatments for NL reported in the literature, all with varying efficacy. Although NL lesions are usually asymptomatic, patients with NL must be monitored closely for signs of ulceration or malignant transformation, in which case more aggressive treatment options may be warranted.

The pathophysiology of generalized essential telangiectasia is not well understood. Generalized essential telangiectasia is an uncommon disorder in which widespread telangiectasias of unknown cause develop without associated systemic or antecedent dermatologic disease. We report a case of generalized essential telangiectasia in an otherwise healthy 49-year-old man.

Lymphomatoid papulosis is often regarded as a low-grade variant of cutaneous T cell lymphoma (CTCL). Given the excellent long-term prognosis, recent consensus guidelines indicate that patients can be monitored off therapy. We report a case of a 67-year-old man who presented with lymphomatoid papulosis, with necrotic papules that have been intermittently present for over forty years.