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Introduction
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June 2003 - January 2006
October 2010 - December 2014
July 2016 - June 2020
Publications
Publications (25)
Our genomes influence nearly every aspect of human biology-from molecular and cellular functions to phenotypes in health and disease. Studying the differences in DNA sequence between individuals (genomic variation) could reveal previously unknown mechanisms of human biology, uncover the basis of genetic predispositions to diseases, and guide the de...
Radiation-associated sarcomas are an uncommon complication of therapeutic radiation. However, their prevalence has increased with the more widespread use of this treatment modality. The clinical, pathologic and genetic characteristics of radiation-associated sarcomas are not fully understood. In this study we describe the features of 94 radiation-a...
A central problem in genomics is understanding the effect of individual DNA variants. Multiplexed Assays of Variant Effect (MAVEs) can help address this challenge by measuring all possible single nucleotide variant effects in a gene or regulatory sequence simultaneously. Here we describe MaveDB v2, which has become the database of record for MAVEs....
Across 20 vaccine breakthrough cases detected at our institution, all 20 (100%) infections were due to variants of concern (VOC) and had a median Ct of 20.2 (IQR=17.1-23.3). When compared to 5174 contemporaneous samples sequenced in our laboratory, VOC were significantly enriched among breakthrough infections (p < .05).
Across 20 vaccine breakthrough cases detected at our institution, all 20 (100%) infections were due to variants of concern (VOC) and had a median Ct of 20.2 (IQR=17.1-23.3). When compared to 5174 contemporaneous samples sequenced in our laboratory, VOC were significantly enriched among breakthrough infections (p < .05).
Genetic data are rapidly becoming part of tumor classification and are integral to prognosis and predicting response to therapy. Current molecular tumor profiling relies heavily on tissue resection or biopsy. Tissue profiling has several disadvantages in tumors of the central nervous system, including the challenge associated with invasive biopsy,...
Introduction
Glioblastoma multiforme (GBM) is the most aggressive and most common primary brain tumor. Treatment of GBM and other high-grade gliomas consists of surgical resection followed by radiation and temozolomide (TMZ) chemotherapy. TMZ alkylates purine DNA bases, causing DNA damage and eventually cell death. Alkylation at O6-gauanine can be...
Distinguishing neoplastic from reactive cutaneous lymphoid infiltrates remains a diagnostic challenge. While flow cytometry is broadly used in hematopathology, it is only now emerging as a method for determining the immunophenotype and clonality of cutaneous lymphocyte populations. Cutaneous marginal zone lymphomas are particularly challenging; the...
E-cadherin is highly phosphorylated within its β-catenin binding region, and this phosphorylation increases its affinity for β-catenin in vitro. However, the identification of key serines responsible for most cadherin phosphorylation and the adhesive consequences of modification at such serines have remained unknown. In this study, we show that as...
Expression analysis of GFP-ZFN2 linker variants.
Inter-finger linker strategy to expand target half-sites from 9 to 10 bp.
Amino acid sequence of GFP-ZFN2 DNA-binding domain.
Nuclease activities of GFP-ZFN2 inter-finger linker variants.
Recent studies have shown that zinc finger nucleases (ZFNs) are powerful reagents for making site-specific genomic modifications. The generic structure of these enzymes includes a ZF DNA-binding domain and nuclease domain (Fn) are separated by an amino acid "linker" and cut genomic DNA at sites that have a generic structure (site1)-(spacer)-(site2)...
The cadherin/catenin complex organizes to form a structural Velcro that joins the cytoskeletal networks of adjacent cells. Functional loss of this complex arrests the development of normal tissue organization, and years of research have gone into teasing out how the physical structure of adhesions conveys information to the cell interior. Evidence...
Agarose-gel electrophoresis has been used for more than thirty years to characterize the linking-number (Lk) distribution of closed-circular DNA molecules. Although the physical basis of this technique remains poorly understood, the gel-electrophoretic behavior of covalently closed DNAs has been used to determine the local unwinding of DNA by prote...
Comparison of calculated enhanced repression as a function of operator spacing with the in-vivo data of Müller et al. [4]
(0.27 MB DOC)
Supporting information for “Analysis of In-Vivo LacR-Mediated Gene Repression Based on the Mechanics of DNA Looping” by Yongli Zhang, Abbye E. McEwen, Donald M. Crothers, and Stephen D. Levene.
(0.31 MB DOC)
Comparison of calculated enhanced repression as a function of operator spacing with the in-vivo data of Becker et al. [5] for wild-type (WT) and HU-deletion (ΔHU) E. coli strains.
(0.27 MB DOC)
The lack of a rigorous analytical theory for DNA looping has caused many DNA-loop-mediated phenomena to be interpreted using theories describing the related process of DNA cyclization. However, distinctions in the mechanics of DNA looping versus cyclization can have profound quantitative effects on the thermodynamics of loop closure. We have extend...
Interactions of E. coli lac repressor (LacR) with a pair of operator sites on the same DNA molecule can lead to the formation of looped nucleoprotein complexes both in vitro and in vivo. As a major paradigm for loop-mediated gene regulation, parameters such as operator affinity and spacing, repressor concentration, and DNA bending induced by specif...
