Publications

Midline defects account for approximately 5% of congenital abnormalities observed at birth. However, the molecular mechanisms underlying the formation of the ventral body wall are not well understood. Recent studies linked mutations in Porcupine-an O-acetyl transferase mediating Wnt ligand acylation-with defects in the thoracic body wall. We hypothesized that anomalous Wnt signaling is involved in the pathogenesis of defective closure of the thoracic body wall.

Staphylococcus aureus is an important cause of human skin and soft tissue infections (SSTIs) globally. Notably, 80% of all SSTIs are caused by S. aureus, of which ∼63% are abscesses and/or cellulitis. Although progress has been made, our knowledge of the host and pathogen factors that contribute to the pathogenesis of SSTIs is incomplete. To provide a more comprehensive view of this process, we monitored changes in the S. aureus transcriptome and selected host proinflammatory molecules during abscess formation and resolution in a rabbit skin infection model. Within the first 24 h, S.

OBJECTIVE: Assess human papilloma virus (HPV) transcriptional activity in inverted Schneiderian papillomas (IPs). STUDY DESIGN: Case series with chart review. SETTING: Academic tertiary care center. SUBJECTS AND METHODS: Retrospective clinicopathologic review of 19 cases of IP in patients undergoing surgical excision from 1995 to 2013 at Mayo Clinic in Rochester, Minnesota. Surgical pathology archival material was histopathologically reviewed using hematoxylin and eosin-stained slides.

LGR5 is known to be a stem cell marker in the murine small intestine and colon, however the localization of LGR5 in human adenoma samples has not been examined in detail, and previous studies have been limited by the lack of specific antibodies. Here we used in situ hybridization to specifically examine LGR5 mRNA expression in a panel of human adenoma and carcinoma samples (n = 66). We found that a small number of cells express LGR5 at the base of normal colonic crypts.

Circuit computation requires precision in the timing, extent, and synchrony of principal cell (PC) firing that is largely enforced by parvalbumin-expressing, fast-spiking interneurons (PVFSIs). To reliably coordinate network activity, PVFSIs exhibit specialized synaptic and membrane properties that promote efficient afferent recruitment such as expression of high-conductance, rapidly gating, GluA4-containing AMPA receptors (AMPARs). We found that PVFSIs upregulate GluA4 during the second postnatal week coincident with increases in the AMPAR clustering proteins NPTX2 and NPTXR.

Expression of HOX transcript antisense intergenic RNA (HOTAIR), a large intergenic noncoding RNA (lincRNA), has been described as a metastases-associated lincRNA in various cancers including breast, liver and colon cancer cancers. We sought to determine if expression of HOTAIR could be used as a surrogate for assessing nodal metastases and evaluated RNA in situ hybridization (RNA-ISH) assay in a tissue microarray constructed from 133 breast cancer patients. The prognostic value of HOTAIR was further validated in large cohorts using The Cancer Genome Atlas (TCGA) breast cancer subjects.

Mutations in the secreted glycoprotein ADAMTSL2 cause recessive geleophysic dysplasia (GD) in humans and Musladin-Lueke syndrome (MLS) in dogs. GD is a severe, often lethal condition presenting with short stature, brachydactyly, stiff skin, joint contractures, tracheal-bronchial stenosis, and cardiac valve anomalies, whereas MLS is non-lethal and characterized by short stature and severe skin fibrosis.

The primary cilium is essential for skin morphogenesis through regulating the Notch, Wnt, and hedgehog signaling pathways. Prior studies on the functions of primary cilia in the skin were based on the investigations of genes that are essential for cilium formation. However, none of these ciliogenic genes has been linked to ciliopathy, a group of disorders caused by abnormal formation or function of cilia.

While WHO grade I meningiomas are considered benign, patients with WHO grade III meningiomas have very high mortality. The principles underlying tumor progression in meningioma are largely unknown yet a detailed understanding of these mechanisms will be required for effective management of patients with these high-grade, lethal tumors. We present a case of an intraventricular meningioma that at first presentation displayed remarkable morphologic heterogeneity – comprised of distinct regions independently fulfilling histopathologic criteria for WHO grade I, II and III designations.

While thousands of long noncoding RNAs (lncRNAs) have been identified, few lncRNAs that control neural stem cell (NSC) behavior are known. Here, we identify Pinky (Pnky) as a neural-specific lncRNA that regulates neurogenesis from NSCs in the embryonic and postnatal brain. In postnatal NSCs, Pnky knockdown potentiates neuronal lineage commitment and expands the transit-amplifying cell population, increasing neuron production several-fold. Pnky is evolutionarily conserved and expressed in NSCs of the developing human brain.