Brooke Harmon

Biography

During Harmon’s graduate work, in the lab of Lee Ratner, MD, PhD., at Washington University School of Medicine, she determined the cellular signaling factors required for HIV-1 virus-cell fusion, identified small molecule inhibitors that block these host proteins, and determined the mechanism of action of these drugs. Many of these proteins are also dysregulated in a number of cancers. The results from these studies were published in Journal of Virology and Plos Pathogens and were also presented at multiple internal and external conferences.

As a postdoctoral fellow at Sandia, Harmon used robotic high-throughput automated liquid handling equipment to perform a genome-wide RNA interference screen to identify host factors involved in Rift Valley fever virus (RVFV) infection. During the course of this screen she designed, optimized, and implemented robust methods to discover biomarkers and relevant host factors that could be targeted by therapeutic agents. She then used state-of the-art bioinformatic tools to perform statistical analysis of the complex data sets generated. To validate targets identified in this screen, Harmon used small molecule inhibitors, siRNA, and dominant mutant protein overexpression to demonstrate that RVFV enters mammalian cells via caveolae-mediated endocytosis and Wnt/β-catenin signaling is important for bunyaviral infection, these results were published in the Journal of Virology in December 2012 and July 2016. As a postdoc, Harmon also contributed to several multidisciplinary projects across Sandia National Laboratioes, leading to the development of a microfluidic device that examines cellular pathways involved in viral and bacterial pathogenesis, a device that mimics the human lung to investigate tissue level responses to pathogen and drug exposures, the identification of distinct domains within viral proteins required for anti-interferon activity, and the discovery of signaling mediators involved in long term and short term immune memory in mast cells. In all, these discoveries resulted in 6 publications in peer-reviewed journals, 4 presentations at major conferences, and 1 patent application.

Education

Bachelor’s Degree: Microbiology, Immunology, and Molecular Genetics; University of California, Los Angeles (1999-2002)

Doctoral Degree: Molecular Microbiology & Microbial Pathogenesis; Washington University, St. Louis, MO (2003-2009)

Postdoctoral Fellowships: Sandia National Laboratories (2010-2014)

Research Interests

Harmon has published several peer reviewed manuscripts on cell signaling pathways and virus-host interactions. She has extensive experience in gene editing, molecular biology, high throughput screening, and virus entry mechanisms. Since becoming a Senior Member of the Technical Staff in 2014, her research has focused on the development and use of a target-based drug discovery pipeline for identification of countermeasures against emerging viruses, and other evolving biodefense targets, as well as the development of methods for controlling the activity of novel gene editing tools.

Selected Publications

• Phaneuf CR, Seamon KJ, Eckles TP, Sinha A, Schoeniger JS, Harmon B, Meagher RJ, Abhyankar VV, Koh CY. Ultrasensitive Multi-Species Detection of CRISPR-Cas9 by Portable Centrifugal Microfluidic Platform. Analytical Methods (2019) DOI 10.1039/c8ay02726a
• Kyle J. Seamon KJ, Light YK, Saada EA, Schoeniger JS, and Harmon B*. Versatile High-Throughput Fluorescence Assay for Monitoring Cas9 Activity. (2018) Analytical Chemistry May 24; 90 (11): 6913-6921
• Harmon B, Chylek L, Liu Y, Mahajan A, Schudel BR, Holowka D, Baird B, Wilson B, Hlavacek W, Singh AK. Timescale Separation of Positive and Negative Signaling Creates History-Dependent Responses to IgE Receptor Stimulation. (2017) Scientific Reports. Nov 11; 7 (1) 15586-2
• Harmon B, Bird SW, Schudel BR, Hatch AV, Rasley A, Negrete OA. A Genome-Wide RNA Interference Screen Identifies a Role for Wnt/β-Catenin Signaling during Rift Valley Fever Virus Infection. (2016) Journal of Virology. Jul 27; 90 (16): 7084-97.
• Harmon B, Kozina C, Maar D, Carpenter ST, Branda C, Negrete OA, Carson B. Identification of Critical Amino Acids within the Nucleoprotein of Tacaribe Virus Important for Anti-Interferon Activity. (2013) Journal of Biological Chemistry. Mar 22; 288 (12): 8702-11.
• Schudel BR, Harmon B, Pruitt B, Abhyankar V, Negrete OA, Singh AK. Microfluidic platforms for RNA Interference screening of virus-host interactions. (2013) Lab Chip. Feb 5;13 (5) :811-7.
• Harmon B, Schudel BR, Maar D, Kozina C, Ikegami T, Tseng C, Negrete OA. Rift Valley fever virus strain MP-12 enters mammalian host cells via caveolae-mediated endocytosis. (2012) Journal of Virology. Dec; 86 (23): 12954-70.
• Maar D, Harmon B, Chu D, Shultz B, Aguilar HC, Lee B, Negrete OA. Cysteines in the stalk domain of the Nipah virus G glycoprotein are located in a distinct subdomain critical for fusion activation. (2012) Journal of Virology. Jun; 86 (12): 6632-42.
• Harmon, B, Campbell N, and Ratner L. Role of Abl kinase and the Wave2 signaling complex in HIV-1 entry at a post-hemifusion step. (2010) PLoS pathogens. Jun 17; 6 (6) e1000956
• Harmon B, Ratner L. HIV Envelope Induction of the Gαq Signaling Cascade Is Required for Virus Entry. (2008) Journal of Virology. Sep; 82 (18): 9191-205
• Pontow S, Harmon B, Campbell N, Ratner L. Antiviral Activity of a Rac GEF Inhibitor Characterized with a Sensitive HIV/SIV Fusion Assay. (2007) Virology. Nov 10; 368 (1): 1-6.

Selected Scientific Meetings/Presentations

• Saada EA, Schoeniger JS, Negrete OA, and Harmon B*. Identification of Broad Spectrum Inhibitors of Alphaviruses Using High-Throughput Screening. Chemical and Biological Defense Science and Technology Conference. November 2017. Long Beach, CA.
• Saada E, Negrete O, Harmon B*. Discovery of Anti-Viral Inhibitors against the Chikungunya Virus nsP2 Protease Domain. Keystone symposium on Positive-Strand RNA Viruses. May 2016, Austin, TX.
• Harmon B, Schudel BR, Hatch A, Negrete OA. Genome-wide RNAi screen reveals that activation of the WNT/β-catenin signaling pathway enhances bunyaviral replication. International Union of Microbial Societies Congress of Virology. July 2014. Montreal, Canada.
• Harmon B, Maar D, Tseng C, Ikegami T, Negrete OA. Rift Valley Fever virus enters host cells through caveolin-mediated endocytosis. Keystone symposium: Cell Biology of Virus Entry, Replication and Pathogenesis. March 2012. Whistler, British Columbia, Canada.
• Harmon B, Tseng C, Negrete OA. Genome-wide RNA interference screen identifies caveolae-mediated endocytosis as an entry route for Rift Valley Fever Virus. International Union of Microbial Societies Congress of Virology. September 2011. Sapporo, Japan.
• Harmon B, Tseng C, Negrete OA. Genome-wide RNA interference screen for host factors required for Rift Valley Fever Virus infection. Chemical and Biological Defense Science and Technology Conference. November 2010. Orlando, Florida.
• Harmon B, Ratner L. HIV Envelope Induction of the Gαq Signaling Pathway is Required for Virus Entry. Cold Spring Harbor Retroviruses Meeting. May 2008. Cold Spring Harbor, New York.