Kristina Herbert, Ph.D.

Kristina Herbert's Research Focus

Infectious Diseases, Cancer
Host-Pathogen Interactions, Innate Immunity, RNA-Based Gene Regulation
Cultured Cell Lines, Human Cell Lines, Insect Cell Lines, Mouse Embryonic Stem Cells, Primary Cells, Primary Human Cells
Biochemistry, Bioinformatics, Biophysics, Gene Expression, Gene Silencing, Mass Spectrometry, RNA Interference (RNAi), Systems Biology

Observations of gene silencing by RNA interference-like (RNAi) mechanisms were first made in 1992 in plants and fungi, where they were believed to be ancient defense mechanisms protecting genome integrity against invading DNA from transposons and viruses. The mechanisms by which RNAi worked were later elucidated in C. elegans where it was shown that endogenously encoded small RNAs, known as microRNAs (miRNAs), could down-regulate the expression target genes. These endogenous small RNAs (sRNAs) were soon after discovered in a diverse set of organisms ranging from fungi, plants, flies, and mammals. In the Herbert lab work is focused on characterizing the expression, regulation, and function of sRNAs in microbial pathogens and disease, with a particular focus on viruses.

Kristina Herbert's Research Report

MiRNAs have even been discovered in viral genomes; which normally make use of the host gene expression and small RNA biogenesis proteins in order to express sRNAs from their own genome. As of 2011 nearly 95% of all known viral miRNAs were from the double stranded DNA herpesviruses, where the viral miRNAs have been primarily found to help the virus circumvent the host immune response. sRNAs have also been discovered in RNA viruses, however, it is not clear how they are made or function. Unlike the DNA viruses, the small RNAs from RNA viruses are thought to participate in activating the host immune response. A clearer picture of the biogenesis pathways and sRNA function is required in order to understand how these sRNAs contribute to viral pathogenicity and how they might be targeted for therapeutics.

Kristina Herbert's Bio

I earned my B.A. in Biochemistry and Biophysics from the University of Pennsylvania in Philadelphia, Pennsylvania, USA. During my 4 years there I worked in the laboratory of Dr. Ponzy Lu in the Department of Chemistry. For three years, I studied the binding properties of Lac repressor mutants to operator DNA, and for my senior research project I helped to determine the solution structure of Adenine (A) tract DNA using NMR (MacDonald, Herbert et al. 2001). After graduating, I went for a year on a Fulbright Fellowship, to work in The European Molecular Biology Laboratory in Heidelberg, Germany with Drs. Heinrich Hörber and Matti Saraste. During this year I used an atomic force microscope in force spectroscopy mode to determine unfolding intermediates of concatenated spectrin domains (Altmann, Grunberg et al. 2002). I then returned to the U.S. to do my graduate training in the laboratory of Dr. Steven M. Block at Stanford University in Stanford, California. There I used a single molecule optical trapping assay to study bacterial RNA polymerase elongation. My thesis work entailed developing a novel technique that allowed pauses observed in records of transcription by single bacterial RNA polymerase (RNAP) molecules to be localized to their template positions, with nearly base-pair accuracy over a ~2000 basepair region (Herbert, La Porta et al. 2006, Herbert, Greenleaf et al. 2008, Herbert, Zhou et al. 2010). I completed a postdoctoral fellowship in the laboratory of Dr. Joan A. Steitz at Yale University in New Haven, Connecticut. There I combined proteomics, classical molecular biology, and next generation sequencing of small RNAs to map and characterize the biological impact of post-translational modifications on DGCR8, a critical component of the Microprocessor complex, which processes primary microRNAs in mammalian nuclei (Herbert, Pimienta, et al. 2013). In collaboration with Dr. Keir C. Neuman of the NIH, I also used a single molecule photobleachi ng technique to structurally characterize the Microprocessor complex (Herbert, Sarkar, et al. 2016). This project was finished in my most recent position as an independent investigator at the Ensenada Center for Scientific Research and Higher Education (CICESE) where I ran my own lab in the Department of Microbiology. I returned to pursue research in the US as faculty at the Sanford Burnham Prebys Medical Discovery Institute in 2016.

 

Education

B.A., 1996-2000, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Fulbright Fellow, 2000-2001, The European Molecular Biology Lab, Heidelberg, Germany
Ph.D., 2001-2008, Stanford University, Stanford, California, USA
Postdoctoral Fellow, 2008-2014, Yale University, New Haven, Connecticut, USA
Principal Investigator Titular A, 2014-2016, CICESE, Ensenada, Baja California, México

 

Awards

  • SEP-CONACYT Basic Science CB-2015-01-251974 (2016-2018). Amount: MXN 1,500,000 = ~USD $90,000. Title: “Characterization of protein:RNA complexes contained in exosomes secreted by herpes-virus infected cells”. PI: K.M. Herbert. (forfeited upon moving institutions)
  • CONACYT Infrastructure 2015-253593 (2015-2016). Amount: MXN 10,000,000 = ~USD $600,000. Title: “High Performance Computing Equipment for Strengthening Research in Genomics, Transcriptomics and Proteomics in the Northwest Region of Mexico.” PI: G. Pimienta Rosales. Co-investigator: K.M. Herbert.
  • Burroughs Wellcome Fund Collaborative Research Travel Grant, 2011, Amount: $10,000 for travel between Yale and a collaborator’s laboratory at the NIH. Title: “Establishing the stoichiometry of Drosha and DGCR8 within the Microprocessor Complex through single-molecule subunit counting by fluorescence photobleaching”. PI: K.M. Herbert.

 

Honors and Recognition

  • Howard Hughes Medical Institute Fellow of the Damon Runyon Cancer Research Foundation, 2009-2011 
  • Burroughs Wellcome Fund Career Award at the Scientific Interface Finalist, 2012 
  • Burroughs Wellcome Fund Collaborative Research Travel Grant, 2011 
  • American Cancer Society Postdoctoral Fellowship (declined), 2009 
  • Howard Hughes Medical Institute Predoctoral Fellow, 2000-2006 
  • Student Travel Award for the 50th annual Biophysical Society Meeting, 2006 
  • National Science Foundation Predoctoral Fellowship (declined), 2000 
  • Fulbright Fellow, 2000-2001

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Publications

A heterotrimer model of the complete Microprocessor complex revealed by single-molecule subunit counting.

Herbert KM, Sarkar SK, Mills M, Delgado De la Herran HC, Neuman KC, Steitz JA

RNA 2016 Feb ;22(2):175-83

Phosphorylation of DGCR8 increases its intracellular stability and induces a progrowth miRNA profile.

Herbert KM, Pimienta G, DeGregorio SJ, Alexandrov A, Steitz JA

Cell Rep 2013 Nov 27 ;5(4):1070-81

Sequence-resolved detection of pausing by single RNA polymerase molecules.

Herbert KM, La Porta A, Wong BJ, Mooney RA, Neuman KC, Landick R, Block SM

Cell 2006 Jun 16 ;125(6):1083-94

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Correction to "Strong, Rebondable, Dynamic Cross-Linked Cellulose Nanocrystal Polymer Nanocomposite Adhesives".

Cudjoe E, Herbert KM, Rowan SJ

ACS Appl Mater Interfaces 2019 Jul 10 ;11(27):24820

HIV-1 Vpu is a potent transcriptional suppressor of NF-κB-elicited antiviral immune responses.

Langer S, Hammer C, Hopfensperger K, Klein L, Hotter D, De Jesus PD, Herbert KM, Pache L, Smith N, van der Merwe JA, Chanda SK, Fellay J, Kirchhoff F, Sauter D

Elife 2019 Feb 5 ;8

Strong, Rebondable, Dynamic Cross-Linked Cellulose Nanocrystal Polymer Nanocomposite Adhesives.

Cudjoe E, Herbert KM, Rowan SJ

ACS Appl Mater Interfaces 2018 Sep 12 ;10(36):30723-30731

Noncanonical function of DGCR8 controls mESC exit from pluripotency.

Cirera-Salinas D, Yu J, Bodak M, Ngondo RP, Herbert KM, Ciaudo C

J Cell Biol 2017 Feb ;216(2):355-366

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