Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but extremely lethal ovarian cancer in young women due to lack of effective treatment. Our current study suggests that SCCOHT tumor cells need the activity of an enzyme called EZH2 for their survival. This enzyme adds methyl groups to the dedicated site of histones, a group of proteins that maintain the proper structure of DNA, and thereby controls which genes to turn on or off. Two EZH2 inhibitors, both in various clinical...
Cancer cells have been observed to frequently have amplified centrosomes. These amplified centrosomes must be actively clustered together for cancer cells to divide. Since normal cells do not have centrosome amplification, targeting centrosome clustering is a highly specific way to target cancer cells while sparing normal cells. We performed an automated screen for compounds that inhibited centrosome clustering and identified a Stat3 inhibitor. We are currently trying...
Frontotemporal lobar degeneration with tau-negative, ubiquitin-immunoreactive (-ir) pathology (FTLD-U) is subclassified based on the type and cortical laminar distribution of neuronal inclusions. Following the discovery of the transactive response DNA-binding protein Mr 43 kD (TDP-43) as the ubiquitinated protein in most FTLD-U, the same pathological criteria have been used to classify FTLD cases based on TDP-43-ir changes. However, the fact…
We studied the whole-genome point mutation and structural variation patterns of 133 tumors (59 high-grade serous (HGSC), 35 clear cell (CCOC), 29 endometrioid (ENOC), and 10 adult granulosa cell (GCT)) as a substrate for class discovery in ovarian cancer. Ab initio clustering of integrated point mutation and structural variation signatures identified seven subgroups both between and within histotypes. Prevalence of…
During pancreatic development, proliferating pancreatic progenitors activate the proendocrine transcription factor neurogenin 3 (NEUROG3), exit the cell cycle, and differentiate into islet cells. The mechanisms that direct robust NEUROG3 expression within a subset of progenitor cells control the size of the endocrine population. Here we demonstrate that NEUROG3 is phosphorylated within the nucleus on serine 183, which catalyzes its hyperphosphorylation…
Human papillomavirus (HPV) vaccines were originally approved with 3-dose schedules. However, 2 doses of HPV vaccine have been recommended1 for girls younger than 15 years based on antibody response at 36 months,2,3although continued research on the duration of antibody persistence was advised. We report antibody response at 60 months after 2 doses of quadrivalent HPV vaccine. Read More
My team focuses on development of novel innovative technology for cancer therapeutics and diagnostics. A major focus of the lab is on the identification of oncofetal proteins and secondary protein modifications such as glycosylation’s that can be potentially exploited as cancer targets in the clinic. We are more technology focused than disease focused in the sense that we are generally...
An early report on the molecular subtyping of muscle-invasive bladder cancer (MIBC) by gene expression suggested that response to neoadjuvant chemotherapy (NAC) varies by subtype. To investigate the ability of molecular subtypes to predict pathological downstaging and survival after NAC. Whole transcriptome profiling was performed on pre-NAC transurethral resection specimens from 343 patients with MIBC. Samples were classified according to four published…
Tyrosine kinase inhibitor (TKI) therapies induce clinical remission with remarkable effects on chronic myeloid leukemia (CML). However, very few TKIs completely eradicate the leukemic clone and persistence of leukemic stem cells (LSCs) remains challenging, warranting new, distinct targets for improved treatments. We demonstrated that the scaffold protein AHI-1 is highly deregulated in LSCs and interacts with multiple proteins, including Dynamin-2…
Alterations in cellular aging, indexed by leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn), might partly account for the increased health risks in persons with depression. Although some studies indeed found cross-sectional associations of depression with LTL and mtDNAcn, the longitudinal associations remain unclear. This 10-year longitudinal study examined between- and within-person associations of depressive symptoms with LTL…