A5061783891- BRCA gene mutations in cancer
- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- Genetic factors in colorectal cancer
- Prostate Cancer Treatment and Research
- Nutrition, Genetics, and Disease
- Epigenetics and DNA Methylation
- Ethics in Clinical Research
- Genomic variations and chromosomal abnormalities
- Prostate Cancer Diagnosis and Treatment
- Virus-based gene therapy research
- Genetic Associations and Epidemiology
- Molecular Biology Techniques and Applications
- Pancreatic and Hepatic Oncology Research
- CRISPR and Genetic Engineering
- Cancer, Lipids, and Metabolism
- Genomics and Rare Diseases
- Cancer Immunotherapy and Biomarkers
- RNA Research and Splicing
- Ovarian cancer diagnosis and treatment
- COVID-19 and healthcare impacts
- Hedgehog Signaling Pathway Studies
- Neuroblastoma Research and Treatments
University of Pennsylvania
2016-2025
Philadelphia VA Medical Center
2021-2025
Children's Hospital of Philadelphia
2018-2025
Veterans Health Administration
2025
Hospital of the University of Pennsylvania
2020-2025
University of Pennsylvania Health System
2021-2024
Abramson Cancer Center
2022-2024
Philadelphia University
2024
Cancer Research Institute
2023-2024
Newfoundland and Labrador Centre for Applied Health Research
2023
Proprotein convertase subtilisin kexin 9 (Pcsk9) is a serine protease with putative role in cholesterol metabolism. Pcsk9 expression down-regulated by dietary cholesterol, and mutations have been associated form of autosomal dominant hypercholesterolemia. To study the function mice, an adenovirus constitutively expressing murine (Pcsk9-Ad) was used. overexpression wild-type mice caused 2-fold increase plasma total 5-fold non-high-density lipoprotein (HDL) no HDL as compared infected control...
Patients with cancer have high mortality from coronavirus disease 2019 (COVID-19), and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 patients who were hospitalized for COVID-19, hematologic had higher relative to solid cancer. two additional cohorts, flow cytometric serologic analyses demonstrated without similar phenotype during acute whereas impairment B cells severe respiratory syndrome 2 (SARS-CoV-2)-specific antibody responses. Despite impaired...
Proprotein convertase subtilisin kexin 9 (PCSK9) is a member of the serine protease family with an important role in cholesterol metabolism. PCSK9 expression regulated by dietary mice and cellular sterol levels cell culture via regulatory element binding protein transcription factors, mutations are associated form autosomal dominant hypercholesterolemia. Overexpression leads to increased total low-density lipoprotein (LDL) because decrease hepatic LDL receptor (LDLR) normal mRNA levels. To...
Complete loss of BRCA1 or BRCA2 function is associated with sensitivity to DNA damaging agents. However, not all and germline mutation-associated tumors respond. Herein we report analyses 160 breast ovarian tumors. Retention the normal allele (absence locus-specific heterozygosity (LOH)) observed in 7% ovarian, 16% 10% breast, 46% These have equivalent homologous recombination deficiency scores sporadic tumors, significantly lower than LOH (ovarian, P = 0.0004; < 0.0001, two-tailed Student's...
The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic/likely pathogenic (P/LP) variants associated with increased risk breast, ovarian, pancreatic, prostate cancer, including BRCA1 , BRCA2 CDH1 PALB2 PTEN TP53 recommended approaches to genetic counseling/testing care strategies in individuals these P/LP variants. These Insights summarize important updates regarding: (1) a new section transgender, nonbinary...
Understanding the gene-specific risks for development of breast cancer will lead to improved clinical care those carrying germline mutations in predisposition genes. We sought detail spectrum and refine risk estimates known proposed susceptibility Targeted massively-parallel sequencing was performed identify copy number variants 26 or genes 2134 BRCA1/2-negative women with familial (proband a family history ovarian cancer) from largely European-Caucasian multi-institutional cohort....
Background A number of epidemiological and genetic studies have attempted to determine whether levels circulating lipids are associated with risks various cancers, including breast cancer (BC). However, it remains unclear a causal relationship exists between BC. If alteration lipid also reduced risk BC, this could present target for disease prevention. This study aimed assess potential variants plasma traits (high-density lipoprotein, HDL; low-density LDL; triglycerides, TGs) BC using...
Nearly all breast cancer deaths result from metastatic disease. Despite this, the genomic events that drive recurrence are poorly understood. We performed whole-exome and shallow whole-genome sequencing to identify genes pathways preferentially mutated or copy-number altered in metastases compared with paired primary tumors which they arose. Seven were - MYLK, PEAK1, SLC2A4RG, EVC2, XIRP2, PALB2, ESR1 5 of not significantly any type human cancer. Four regions altered: loss STK11 CDKN2A/B, as...
<h3>Importance</h3> Li-Fraumeni syndrome is a cancer predisposition that associated with high, lifelong risk of broad spectrum cancers caused by pathogenic<i>TP53</i>germline variants. A definition reflects the phenotypic has evolved since gene discovery lacking, and mechanisms leading to differences remain largely unknown. <h3>Objective</h3> To define conduct phenotype-genotype associations across spectrum. <h3>Design, Setting, Participants</h3> We analyzed classified germline variant data...
Breast cancers with BRCA1/2 alterations have a relatively high mutational load, suggesting that immune checkpoint blockade may be potential treatment option. However, the degree of cell infiltration varies widely, and molecular features contributing to this variability remain unknown.We hypothesized genomic signatures might predict immunogenicity in breast cancers. Using The Cancer Genome Atlas (TCGA) data, we compared (89) without (770) either germline or somatic alterations. We also...
Inherited germline TP53 pathogenic and likely variants (gTP53) cause autosomal dominant multicancer predisposition including Li-Fraumeni syndrome (LFS). However, there is no known association of prostate cancer with gTP53.To determine whether gTP53 predisposes to cancer.This multi-institutional retrospective study characterizes incidence in a cohort LFS males prevalence cohort.We evaluated the spectrum clinical features associated cancer.We identified 31 cases among 163 adult males, 26 54...
With the increasing use of comprehensive germline genetic testing children and adolescents with cancer, it has become evident that pathogenic variants (PV) in adult-onset cancer predisposition genes (aoCPG) underlying syndromes, such as Lynch syndrome or hereditary breast ovarian are enriched reported 1% to 2% cancer. However, causal relationship between PVs aoCPGs childhood is still under investigation. The best-studied examples include heterozygous mismatch repair associated deficient...
The StarD4 and StarD5 proteins share ∼30% identity, each is a steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain. We previously showed expression sterol-repressed, consistent with regulation by sterol element-binding (SREBPs), whereas not sterol-regulated. Here we further address the function of StarD5. Unlike StAR, START family prototype, were induced stimuli in Leydig cells. However, StAR-like activity cell culture steroidogenesis assay, indicating...
Abstract Germline variants in tumor suppressor genes (TSGs) can result RNA mis-splicing and predisposition to cancer. However, identification of that impact splicing remains a challenge, contributing substantial proportion patients with suspected hereditary cancer syndromes remaining without molecular diagnosis. To address this, we used capture RNA-sequencing (RNA-seq) generate profile 18 TSGs ( APC , ATM BRCA1 BRCA2 BRIP1 CDH1 CHEK2 MLH1 MSH2 MSH6 MUTYH NF1 PALB2 PMS2 PTEN RAD51C RAD51D...
Cancer patients have increased morbidity and mortality from Coronavirus Disease 2019 (COVID-19), but the underlying immune mechanisms are unknown. In a cohort of 100 cancer hospitalized for COVID-19 at University Pennsylvania Health System, we found that with hematologic cancers had significantly higher relative to solid after accounting confounders including ECOG performance status active status. We performed flow cytometric serologic analyses 106 113 non-cancer controls two additional...
Importance Cetuximab-based and carboplatin-based chemoradiotherapy (CRT) are often used for patients with locally advanced head neck cancer who ineligible cisplatin. There no prospective head-to-head data comparing cetuximab-based regimens radiosensitization. Objective To compare survival CRT in squamous cell carcinoma (HNSCC). Design, Setting, Participants This cohort study included US veterans received a diagnosis of HNSCC between January 2006 December 2020 were treated systemic therapy...