Steven Branda

Biography

Steven Branda is a microbiologist and molecular geneticist with extensive experience in the characterization of bacterial pathogens and their interactions with the host. He has led and contributed to a wide variety of productive research projects, many of which have focused on development and application of specialized sample preparation for time- and cost-efficient analysis of host and pathogen transcriptomes via Next Generation Sequencing (NGS). Other projects have focused on development of microfluidics-based technologies for automated and integrated analysis of complex samples, including clinical specimens, for applications in detection and diagnosis of infectious diseases. His current focus is development of host-directed, CRISPR-based therapies for infectious disease. In collaboration with Dr. Sahar El-Etr, Dr. Magdalena Franco, and Dr. Nicole Collette at Lawrence Livermore National Laboratory (LLNL), he has established and characterized in vitro and in vivo models of Burkholderia thailandensis infection, and in vitro models of B. pseudomallei infection. 

Education

Bachelor’s Degree: Psychobiology, Swarthmore College (1991)

Doctoral Degree: Genetics, Yale University (1999)

Postdoctoral Fellowships:

• Molecular Biology, Yale University (1999-2000)
• Microbiology, Harvard Medical School (2000-2005)

As a postdoctoral fellow in the laboratory of Dr. Roberto Kolter (Harvard Medical School), and in collaboration with postdoctoral fellows in the laboratory of Dr. Richard Losick (Harvard University), Branda established and extensively characterized several complementary models of biofilm formation by the Gram-positive bacterium B. subtilis. Prior to this effort, virtually all studies of bacterial biofilms focused on those produced by Gram-negative bacteria. By describing the defining features of B. subtilis biofilms in detail and, through a combination of genetics and biochemistry, elucidating the major molecular mechanisms and regulators driving their formation, Branda and his colleagues seeded a new branch of biofilm research that continues to flourish to this day.

Research Interests

NGS-enabled Analysis of Pathogen and Host Transcriptomes

The advent of NGS has made possible quantitative analysis of virtually all transcripts produced by a cell, tissue, or organism.  However, brute-force NGS of complex samples is often not time or cost-efficient, particularly when the transcripts of interest are rare (e.g., produced by a pathogen that has infected host cells).  In collaboration with colleagues at Sandia National Laboratories, Branda has developed novel sample preparation methods that enable suppression of highly abundant nucleic acids (e.g., molecular normalization) and enrichment of rare nucleic acids (e.g., probe-mediated capture of pathogen transcripts) for selective NGS analysis. Branda and his colleagues have used these methods for transcriptome profiling of B. pseudomallei and B. thailandensis during infection of human primary cells (manuscript in preparation), of Francisella tularensis and Yersinia enterocolitica during infection of mouse cell lines, and of B. thailandensis during respiratory infection of mice (manuscript in preparation). Additionally, they have used these methods for highly-sensitive detection of viral and bacterial pathogens in blood samples (manuscript in preparation). Others in the field have used their methods for a wide variety of applications.

Relevant Publications:

• VanderNoot VA, Langevin SA, Solberg OD, Lane PD, Curtis DJ, Bent ZW, Williams KP, Patel KD, Schoeniger JS, Branda SS, Lane TW (2012) cDNA normalization by hydroxyapatite chromatography to enrich transcriptome diversity in RNA-Seq applications. BioTechniques 53:373-80.
• Bent ZW, Tran-Gyamfi MB, Langevin SA, Brazel DM, Hamblin RY, Branda SS, Patel KD, Lane TW, Vandernoot VA (2013) Enriching pathogen transcripts from infected samples: A capture-based approach   to enhanced host-pathogen RNA sequencing. Anal Biochem 438:90-6.
• Bent ZW, Brazel DM, Tran-Gyamfi MB, Hamblin RY, VanderNoot VA, Branda SS (2013) Use of a capture-based pathogen transcript enrichment strategy for RNA-Seq analysis of the Francisella tularensis LVS transcriptome during infection of murine macrophages. PLoS ONE 8:e77834.
• Bent ZW, Poorey K, Brazel DM, LaBauve AE, Sinha A, Curtis DJ, House SE, Tew KE, Hamblin RY, Williams KP, Branda SS, Young GM, Meagher RJ (2015) Transcriptomic analysis of Yersinia enterocolitica biovar 1B infecting murine macrophages reveals new mechanisms of extracellular and intracellular survival. Infect Immun 83:2672-85

Microfluidics-Enabled Sample Preparation for Biochemical Analyses

Reliable handling, fractionation, and modification of small biological samples can be exceedingly difficult when using conventional methods. Microfluidics-based methods offer improved precision, and often can be fully automated, but integrating multiple manipulations that together constitute a sample processing pipeline can be challenging, and usually requires a complicated platform architecture (e.g., robotics).  In collaboration with colleagues at Sandia National Laboratories, Branda has developed and validated a variety of microfluidics-based devices for processing of small biological samples (bacteria, mammalian cells, and clinical specimens) for NGS, flow cytometry, and mass spectrometry analyses.  In many cases this required integration of continuous-flow and digital modalities of microfluidics, as well as rational redesign of conventional techniques for microscale implementation. Branda and his colleagues’ approaches to these problems have been adopted by many researchers, and many of their devices and techniques have been patented and licensed.

Relevant Publications:

• Srivastava N, Brennan JS, Renzi RF, Wu M, Branda SS, Singh AK, Herr AE (2009) Fully integrated microfluidic platform enabling automated phosphoprofiling of macrophage response. Anal Chem 81:3261-9.
• Wu M, Perroud TD, Srivastava N, Branda CS, Sale KL, Carson BD, Patel KD, Branda SS, Singh AK (2012) Microfluidically-unified cell culture, sample preparation, imaging, and flow cytometry for measurement of cell signaling pathways with single cell resolution. Lab Chip 12:2823-31.
• Kim H, Jebrail MJ, Sinha A, Bent ZW, Solberg OD, Williams KP, Langevin SA, Renzi RF, Van de Vreugde JL, Meagher RJ, Schoeniger JS, Lane TW, Branda SS, Bartsch MS, Patel KD (2013) A microfluidic DNA library preparation platform for next-generation sequencing. PLoS ONE 8:e68988.
• Jebrail MJ, Sinha A, Vellucci S, Renzi RF, Ambriz C, Gondhalekar C, Schoeniger JS, Patel KD, Branda SS (2014) World-to-digital-microfluidics interface enabling extraction and purification of RNA from human whole blood. Anal Chem 86:3856-62.

Publications

Awards, Honors, and Memberships

• NIH Study Section: NIAID Special Emphasis Panel “NIH Support for Conferences and Scientific Meetings R13/U13” (April 2014)
• NIH Study Section: NIAID Special Emphasis Panel “Partnerships for Interventions to Treat Chronic, Persistent, and Latent Infections R21/R33″(November 2012)
• NIH Study Section: NIAID Special Emphasis Panel “Biofilm P01” (January 2009) Postdoctoral Fellowship, Charles A. King Trust (2003-2005)
• Postdoctoral Fellowship, American Cancer Society (2000-2003)
• Postdoctoral Fellowship, Howard Hughes Medical Institute (1999-2000)
• Predoctoral Fellowship, National Institutes of Health (1994-1997)
• Sigma Xi, The Scientific Research Society (1991)
• Distinction in Course, Swarthmore College (1991)

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