Kael Fischer, PhD
- Gene Expression
- Departments: Pathology - Adjunct Assistant Professor
- Divisions: Microbiology and Immunology
Academic Office Information
School of Medicine
30 N 1900 E, Room: 5B458
Salt Lake City, UT 84132
Research StatementMy lab uses both experimental approaches and bioinformatics to answer questions about viral pathogenesis. We use unbiased molecular approaches to discover novel viruses in clinical materials of interest where there is evidence of acute infection, yet traditional diagnostics do not identify a pathogen. Recently medicine and science have come through an era when it was thought that infectious diseases would soon be largely eradicated or controlled with vaccines and antimicrobials. The AIDS pandemic and the discovery of HIV were a substantial shock to that view. Furthermore, every year new associations are discovered between microbial agents and diseases that were thought to have non-infectious etiologies.
We use two experimental techniques, coupled with a powerful informatics framework that leverages all the viral sequence in GenBank, to directly interrogate interesting specimens that may contain an undetected virus. First, carefully designed long-oligo microarrays can detect patterns that are similar to expected hybridization patterns of know viral taxa. Because of binding energetics on the array, this approach readily detects pathogens which have point mutations that disrupt the binding of validated PCR primers. In addition to detecting such escape-mutants, this approach has been used to discover several novel human and animal viruses over the past few years. The second experimental approach we use is second-generation sequencing of shotgun libraries made directly from clinically important samples. This yields a very large number of relatively short sequence reads which can be directly examined to identify likely viral sequence.
Each of these experimental tactics uses a metagenomic approach, examining RNA and DNA from a complex environment; in our case directly from clinical specimens. The data from both experiments are complex, and sophisticated analysis is required to filter host sequence and recognize enrichment of sequences that may be indicative of the presence of a pathogen. On the gigabase scale, the problem is similar to finding the proverbial needle in a haystack. We use bioinformatics in several powerful ways to find the needle. Every probe on our microarrays is designed to recognize sequence pattern conserved over a particular group of viruses and groups of bright spots can be built up into evidence for the presence of a virus from a particular group. It is critical for analysis of the microarray data or ultra high-throughput sequencing that viral sequence in GenBank and other public databases is coherently linked to a sequence based taxonomy. Development of such a taxonomy is essential and on going in the lab.
|Doctoral Training||University of California
Molecular and Cell Biology
|Undergraduate||University of California
Molecular and Cell Biology
- Bhetariya PJ, Kriesel JD, Fischer KF (). Analysis of Human Endogenous Retrovirus Expression in Multiple Sclerosis Plaques. J Emerg Dis Virol, 3(2).
- Kriesel JD, Bhetariya PJ, Chan BK, Wilson T, Fischer KF (). Enrichment of Retroviral Sequences in Brain Tissue from Patients with Severe Demyelinating Diseases. J Emerg Dis Virol, 3(2).
- Fantin D, Sutton M, Daumann LJ, Fischer KF (). Evaluation of Existing and New Periodic Tables of the Elements for the Chemistry Education of Blind Students. J Chem Educ, 93(6), 1039-1048.
- Chan B, Wilson T, Fischer KF, Kriesel J (). Deep Sequencing to Identify the Causes of Viral Encephalitis. PLoS ONE, 9(4), e93993.
- Thompson JR, Fuchs M, McLane H, Celebi-Toprak F, Fischer KF, Potter JL, Perry KL (). Profiling viral infections in grapevine using a randomly primed reverse transcription-polymerase chain reaction/macroarray multiplex platform. Phytopathology, 104(2), 211-219.
- Kim C, Wilson T, Fischer KF, Williams MA (). Sustained Interactions between T Cell Receptors and Antigens Promote the Differentiation of CD4(+) Memory T Cells. Immunity, 39(3), 508-520.
- Wiles TJ, Norton JP, Russell CW, Dalley BK, Fischer KF, Mulvey MA (). Combining Quantitative Genetic Footprinting and Trait Enrichment Analysis to Identify Fitness Determinants of a Bacterial Pathogen. PLoS Genet, 9(8), e1003716.
- Thompson JR, Fuchs M, Fischer KF, Perry KL (). Macroarray detection of grapevine leafroll-associated viruses. J Virol Methods, 183(2), 161-9.
- Kriesel JD, Hobbs M, Jones BB, Milash B, Nagra RM, Fischer KF (). Deep Sequencing for the Detection of Virus-Like Sequences in the Brains of Patients with Multiple Sclerosis: Detection of GBV-C in Human Brain. PLoS ONE, 7(3), e31886.
- Allred AF, Wu G, Wulan T, Fischer KF, Holbrook MR, Tesh RB, Wang D (). VIPR: A probabilistic algorithm for analysis of microbial detection microarrays. BMC Bioinformatics, 11, 384.
- Dale R Webster, Armin G Hekele, Adam S Lauring, Kael F Fischer, Hao Li, Raul Andino, and Joseph L DeRisi (10/16/2009). An Enhanced Single Base Extension Technique for the Analysis of Complex Viral Populations. PLoS ONE, 4(10), e7453.
- Chiu CY, Greninger AL, Kanada K, Kwok T, Fischer KF, Runckel C, Louie JK, Glaser CA, Yagi S, Schnurr DP, Haggerty TD, Parsonnet J, Ganem D, DeRisi JL (2008 Sep 16). Identification of cardioviruses related to Theiler's murine encephalomyelitis virus in human infections. Proc Natl Acad Sci U S A, 105(37), 14124-9.
- Kistler AL, Gancz A, Clubb S, Skewes-Cox P, Fischer K, Sorber K, Chiu CY, Lublin A, Mechani S, Farnoushi Y, Greninger A, Wen CC, Karlene SB, Ganem D, DeRisi JL (2008). Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: identification of a candidate etiologic agent. Virol J, 5, 88.
- Shock JL, Fischer KF, DeRisi JL (2007). Whole genome analysis of mRNA decay in Plasmodium falciparum reveals a global lengthening of mRNA half-life during the intraerythrocytic development cycle. Genome Biol, 8(7), R134.
- Urisman A, Fischer KF, Chiu CY, Kistler AL, Beck S, Wang D, DeRisi JL (2005). E-Predict: a computational strategy for species identification based on observed DNA microarray hybridization patterns. Genome Biol, 6, R78.
- Miller EJ, Fischer KF, Marqusee S (2002). Experimental evaluation of topological parameters determining protein-folding rates. Proc Natl Acad Sci U S A, 99(16).
- Fischer K, Marqusee S (2000). A rapid test for identification of autonomous folding units in proteins. J Mol Biol, 302(3), 701-712.
- Chamberlain AK, Fischer KF, Reardon D, Handel TM, Marqusee S (1999). Folding of an isolated ribonuclease H core fragment. Protein Sci, 8(11), 2251-2257.
- Fischer K, Urisman A, DeRisi J (). Diagnosis Using Microarrays. In Desk Encyclopedia of General Virology (2010, p. 311). Academic Press.
- Chiu CY, Rouskin S, Koshy A, Urisman A, Fischer K, Yagi S, Schnurr D, Eckburg PB, Tompkins LS, Blackburn BG, Merker JD, Patterson BK, Ganem D, DeRisi JL (2006 Oct 15). Microarray detection of human parainfluenzavirus 4 infection associated with respiratory failure in an immunocompetent adult. Clin Infect Dis, 43(8), e71-6.
- John Kriesel, MD Preetida Bhetariya, PhD Cheryl Palmer, MD Kael F Fischer, PhD (). Microbial Sequences in Multiple Sclerosis Brain Specimens [Abstract]. Open Forum Infectious Diseases, 3(Suppl_1), 2206.
- Nicole Torosin, Kael Fischer, June Round, Leslie A Knapp (). A comparative study of human and howler monkey Toll-Like Receptor 7 under the selective pressure of yellow fever virus [Abstract]. AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, 158, 315.
- Edward Osborne, Anne J Blaschke, Krow Ampofo, Hillary Crandall, Jarrett Killpack, Chris R Stockmann, Andrew P Farrell, Kael F Fischer, Andrew Pavia, Karen Eilbeck, Robert Schlaberg, Mark Yandell, Carrie L Byington (). Shared Genetic Variants Among Streptococcus pneumoniae Isolates Causing Complicated Pneumonia and Empyema in Children [Abstract]. Open Forum Infectious Diseases, 2(suppl 1), 100.
- David Henderson, Michael Reinsel, Kael Fischer, John Hammond (). First detection in the United States of Ligustrum necrotic ringspot virus in Mazus reptans with mild mosaic symptoms, in mixed infection with Cucumber mosaic virus [Abstract]. Plant Disease, 98(10), 1146.
- Henderson DC, Reinsel MD, Fischer KF, Hammond J (). First Detection of Ligustrum necrotic ringspot virus, Cucumber mosaic virus, and Alternanthera mosaic virus in Mazus reptans in the United States [Abstract]. Plant Disease, 98(10), 1446-1446.
- JD Kriesel, PJ Bhetariya, BK Chan, TA Wilson, KF Fischer (). Enrichment of retroviral sequences in brain tissue from patients with progressive multiple sclerosis [Abstract]. MULTIPLE SCLEROSIS JOURNAL, 20, 370.
- John D Kriesel, Benjamin K Chan, Theodore Wilson, Kael F Fischer (). DEEP SEQUENCING OF PRIMARY PROGRESSIVE MULTIPLE SCLEROSIS AND ENCEPHALTITIS BRAIN [Abstract]. MULTIPLE SCLEROSIS JOURNAL, 19(10), 4119.
- Tracy Nicholson, Allyn Spear, Ted Wilson, Kael Fischer, Kay Faaberg, Susan Brockmeier (). Identification and tracking genomic variability using a PRRSV specific microarray platform [Abstract]. American Society for Microbiology General Meeting, 827, 132.
- Hammond J, Henderson DC, Bagewadi B, Fischer KF, Wang D, Melcher U, Perry KL, Jordan RL, Fauquet CM (). Progress in development of a Universal Plant Virus Microarray for the detection and identification of plant viruses [Abstract]. PHYTOPATHOLOGY, 102(7), 49.
- Bagewadi B, Henderson DC, Fischer K, Jordan RL, Wang D, Perry KL, Melcher U, Hammond J, Fauquet CM (). All plant virus chip: Shifting from proof to use [Abstract]. PHYTOPATHOLOGY, 102(7), 155-155.
- KF Fischer (). Bioinformatic analysis of microarray and next generation sequencing data [Abstract]. PHYTOPATHOLOGY, 100(6), S154-S155.
- B Bagewadi, K Fischer, DC Henderson, RL Jordan, D Wang, KL Perry, U Melcher, J Hammond, CM Fauquet (). Universal plant virus microarray development and validation [Abstract]. Phytopathology, 100(6), S154.
- Steve Miller, Chris Barker, Yanxio Hoo, David Erle, Andrea Barczak, Kael Fischer, Joe DeRisi, Charles Chiu (). Establishing a microarray test for pan-viral identification (Virochip) as a core laboratory resource at UCSF [Abstract]. AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 130(3), 475.
- AK Chamberlain, KF Fischer, TM Raschke, S Marqusee (). Partially folded conformations of RNase H [Abstract]. BIOPHYSICAL JOURNAL, 74(2), A11.