A. Cameron Varano

A. Cameron Varano

Virginia Polytechnic Institute and State University

H-index: 7

North America-United States

Professor Information

University

Virginia Polytechnic Institute and State University

Position

Doctoral Candidate

Citations(all)

231

Citations(since 2016)

191

Cited By

117

hIndex(all)

7

hIndex(since 2016)

7

i10Index(all)

7

i10Index(since 2016)

6

Email

University Profile Page

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What is A. Cameron Varano's h-index at Virginia Polytechnic Institute and State University?

The h-index of A. Cameron Varano has been 7 since 2016 and 7 in total.

What is A. Cameron Varano's total number of citations?

A. Cameron Varano has 231 citations in total.

Top articles of A. Cameron Varano

Customizable Cryo-EM chips improve 3D analysis of macromolecules

The field of cryo-EM has seen immense changes in the past decade. These efforts have focused on automating data collection procedures and improving computational routines [1]. However, changes in sample preparation have remained largely unchanged. Typical sample preparation begins with a specimen applied to carbon-based support films containing holes. Then after a gentle blotting procedure, biological macromolecules are rapidly frozen. Alternative materials, such as gold foils and graphene, have begun to replace traditional materials in the cryo-EM field, and have proven useful for sample preparation procedures [2]. However, these substrates remain limited in their ability to mediate ice thickness and protect fragile macromolecules. We aim to develop new tools to help streamline studies for the scientific community.In order to more precisely manage ice thickness and sample integrity, we radically …

Authors

A Cameron Varano,Nick Alden,William Dearnaley,Michael Casasanta,John Damiano,Jennifer McConnell,Madeline Dukes,Deborah F Kelly

Journal

Microscopy and microanalysis

Publish By

Cambridge University Press

Publish Date

2019/8

Liquid-cell electron tomography of biological systems

Liquid-cell electron microscopy is a rapidly growing field in the imaging domain. While real-time observations are readily available to analyze materials and biological systems, these measurementshave been limited to the two-dimensional (2-D) image plane. Here, we introduce an exciting technical advance to image materials in 3-D while enclosed in liquid. The development of liquid-cell electron tomography permitted us to observe and quantify host–pathogen interactions in solution while contained in the vacuum system of the electron microscope. In doing so, we demonstrate new insights for the rules of engagement involving a unique bacteriophage and its host bacterium. A deeper analysis of the genetic content of the phage pathogens revealed structural features of the infectious units while introducing a new paradigm for host interactions. Overall, we demonstrate a technological opportunity to elevate research …

Authors

William J Dearnaley,Beatrice Schleupner,A Cameron Varano,Nick A Alden,Floricel Gonzalez,Michael A Casasanta,Birgit E Scharf,Madeline J Dukes,Deborah F Kelly

Journal

Nano letters

Publish By

American Chemical Society

Publish Date

2019/6/19

Cryo‐Electron Microscopy: Cryo‐EM‐On‐a‐Chip: Custom‐Designed Substrates for the 3D Analysis of Macromolecules (Small 21/2019)

In article number 1900918, Deborah F. Kelly and co-workers develop a new cryo-electron microscopy (EM)-on-a-chip approach. This strategy enables researchers to directly visualize the “fault in our stars” regarding cancer proteins. The structural assemblies of p53 from brain cancer cells are determined for the first time using the microchip-based technique. Artistic rendition by Daryl N. Branford.

Authors

Nick A Alden,A Cameron Varano,William J Dearnaley,Maria J Solares,William Y Luqiu,Yanping Liang,Zhi Sheng,Sarah M McDonald,John Damiano,Jennifer McConnell,Madeline J Dukes,Deborah F Kelly

Journal

Small

Publish Date

2019/5

Cryo‐EM‐On‐a‐Chip: Custom‐Designed Substrates for the 3D Analysis of Macromolecules

The fight against human disease requires a multidisciplinary scientific approach. Applying tools from seemingly unrelated areas, such as materials science and molecular biology, researchers can overcome long‐standing challenges to improve knowledge of molecular pathologies. Here, custom‐designed substrates composed of silicon nitride (SiN) are used to study the 3D attributes of tumor suppressor proteins that function in DNA repair events. New on‐chip preparation strategies enable the isolation of native protein complexes from human cancer cells. Combined techniques of cryo‐electron microscopy (EM) and molecular modeling reveal a new modified form of the p53 tumor suppressor present in aggressive glioblastoma multiforme cancer cells. Taken together, the findings provide a radical new design for cryo‐EM substrates to evaluate the structures of disease‐related macromolecules.

Authors

Nick A Alden,A Cameron Varano,William J Dearnaley,Maria J Solares,William Y Luqiu,Yanping Liang,Zhi Sheng,Sarah M McDonald,John Damiano,Jennifer McConnell,Madeline J Dukes,Deborah F Kelly

Journal

Small

Publish Date

2019/5

Cryo-EM reveals architectural diversity in active rotavirus particles

Rotavirus is a well-studied RNA virus that causes severe gastroenteritis in children. During viral entry, the outer layer of the virion is shed, creating a double-layered particle (DLP) that is competent to perform viral transcription (i.e., mRNA synthesis) and launch infection. While inactive forms of rotavirus DLPs have been structurally characterized in detail, information about the transcriptionally-active DLP remains limited. Here, we used cryo-Electron Microscopy (cryo-EM) and 3D image reconstructions to compare the structures of internal protein components in transcriptionally-active versus inactive DLPs. Our findings showed that transcriptionally-active DLPs gained internal order as mRNA synthesis unfolded, while inactive DLPs remained dynamically disordered. Regions of viral protein/RNA constituents were analyzed across two different axes of symmetry to provide a more comprehensive view of moving …

Authors

Mary Hauser,William J Dearnaley,A Cameron Varano,Michael Casasanta,Sarah M McDonald,Deborah F Kelly

Journal

Computational and Structural Biotechnology Journal

Publish By

Elsevier

Publish Date

2019/1/1

Correcting errors in the BRCA1 warning system

Given its important role in human health and disease, remarkably little is known about the full-length three-dimensional (3D) molecular architecture of the breast cancer type 1 susceptibility protein (BRCA1), or its mechanisms to engage the tumor suppressor, TP53 (p53). Here, we show how a prevalent cancer-related mutation in the C-terminal region of the full-length protein, BRCA15382insC, affects its structural properties, yet can be biochemically corrected to restore its functional capacity. As a downstream consequence of restoring the ubiquitin ligase activity of mutated BRCA15382insC, the DNA repair response of p53 was enhanced in cellular extracts naturally deficient in BRCA1 protein expression. Complementary structural insights of p53 tetramers bound to DNA in different stage of the repair process support these biochemical findings in the context of human cancer cells. Equally important, we show how this …

Authors

Yanping Liang,William J Dearnaley,Nick A Alden,Maria J Solares,Brian L Gilmore,Kevin J Pridham,A Cameron Varano,Zhi Sheng,Elizabeth Alli,Deborah F Kelly

Journal

DNA repair

Publish By

Elsevier

Publish Date

2019/1/1

Revealing Molecular Adversaries of Human Health Using Advanced Imaging Technology

Single particle electron microscopy (EM) allows us to examine the molecular world and gain insights into protein structures implicated in human disease. Visualizing the 3D architecture of the macromolecules can inform drug design and preventative care. While X-ray crystallography and NMR are able to resolve atomic structures, the methodology is better suited for smaller structures with limited flexibility. Single particle EM allows us analyze larger structures that have inherent flexibility. Protein structures can broadly be categorized as symmetry or asymmetric. There are computational advantages when analyzing symmetrical structures. Specifically, structural information can be extrapolated from fewer vantage points. Thus, symmetrical macromolecules are an advantageous for pioneering new methodologies in single particle EM. Rotavirus double layered particles (DLPs) are large macromolecular complexes that display icosahedral symmetry. Previous studies have led to a high resolution structure of transcriptionally inactive rotavirus frozen in time. However, to more fully understand rotavirus we need to examine the structure under transcriptionally active conditions. To expand our understanding, we first evaluated these viral assemblies using cryo-EM under active and inactive conditions. We found both internal and external structural differences. Based on these findings we sought to further our understanding of these nano-machines by developing a liquid cell environment to evaluate their dynamics over time. Our research not only developed a new methodology to evaluate active particles over time, we also found that the mobility of the DLPs …

Authors

Ann Cameron Varano

Publish Date

2018/12/7

Cryo-EM Reveals a Unique BRCA1 Complex in Metastasis

Currently, there remains a critical need for mapping proteins implicated in the progression of cancer. Visualizing the biological complexes that support metastatic disease allows for a greater understanding of personalized and targeted therapies. The Breast Cancer Susceptibility Protein (BRCA1) and its binding partner, the BRCA1-associated Ring Domain protein (BARD1), is one such complex implicated in the progression of breast and ovarian cancers. Due to the size of the protein complex (~ 300 kDa), cryo-Electron Microscopy (cryo-EM) provides the technical framework to better study the structure-function relationship of BRCA1 assemblies within the context of disease. Using silcon nitride (SiN) microchips with integrated microwells, we are able to illuminate the unique features of the BRCA1 protein complex in metastatic breast cancer.We developed a protocol to capture native BRCA1 complexes from human …

Authors

A Cameron Varano,Nick Alden,William Dearnaley,Deborah F Kelly

Journal

Microscopy and Microanalysis

Publish By

Cambridge University Press

Publish Date

2018/8

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