 Michael Fischbach, PhD
|
| Title | Assistant Professor |
|---|
| School | UCSF School of Pharmacy |
|---|
| Department | Bioengineering and Therapeutic Sciences |
|---|
| Address | 1700 4th Street, Byers Hall
San Francisco CA 94158
|
|---|
| Phone | 415-514-9435 |
|---|
|
|
 Overview Natural products -- small molecules from microbes -- are used widely in the clinic as antibiotics, anticancer agents, immunosuppressants, and cholesterol-lowering drugs. Our lab focuses on three emerging principles that are changing our understanding of which microbes make natural products, what roles they play in the biology of their producers, and how best to discover them:
1. Natural products are produced by the human microbiome.
Most known natural products come from exotic soil and marine bacteria. We have recently found that bacteria from a surprisingly underexplored niche -- the human body -- are prolific producers of natural products. We are currently mining gut- and skin-associated bacteria for natural products that play important roles in human physiology and disease.
2. Natural products mediate interactions among microbial species and between microbes and multicellular organisms.
We are particularly interested in the mechanisms by which natural products from the human microbiome mediate interspecies interactions. We are focusing on interactions between gut bacteria and humans that are relevant to human diseases like Crohn's disease and obesity, and on interactions between different species of skin bacteria that likely play a role in susceptibility to infection by bacterial pathogens like Staphylococcus aureus.
3. Connecting natural products to the genes that encode them accelerates discovery.
We are developing a bioinformatic algorithm that automatically identifies clusters of small-molecule-producing genes in bacterial genomes. An early version of this algorithm has already identified thousands of new gene clusters in the ~1000 bacterial genomes sequenced to date, many of them in species from the human microbiome. We are refining this algorithm so it can predict the chemical structure of the small molecule encoded by each gene cluster. In the near future, we believe this tool will provide us the first global view of the small molecules produced by bacteria, which will serve as a powerful predictive tool for our experimental efforts.
Chemistry, Chemical Biology, Microbiology, Human Microbiome, Genetics, Genomics, Biochemistry, Natural Products, Drug Discovery, Antibiotics, Biosynthesis, Metabolism, Bioengineering, Therapeutics
Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications.
Researchers can login to make corrections and additions, or contact us for help.
-
Fischbach MA, Bluestone JA, Lim WA. Cell-based therapeutics: the next pillar of medicine. Sci Transl Med. 2013 Apr 3; 5(179):179ps7.
-
Djonovic S, Urbach JM, Drenkard E, Bush J, Feinbaum R, Ausubel JL, Traficante D, Risech M, Kocks C, Fischbach MA, Priebe GP, Ausubel FM. Trehalose Biosynthesis Promotes Pseudomonas aeruginosa Pathogenicity in Plants. PLoS Pathog. 2013 Mar; 9(3):e1003217.
-
Donia MS, Fischbach MA. Dyeing to Learn More about the Gut Microbiota. Cell Host Microbe. 2013 Feb 13; 13(2):119-20.
-
Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS, Bulaj G, Camarero JA, Campopiano DJ, Challis GL, Clardy J, Cotter PD, Craik DJ, Dawson M, Dittmann E, Donadio S, Dorrestein PC, Entian KD, Fischbach MA, Garavelli JS, Göransson U, Gruber CW, Haft DH, Hemscheidt TK, Hertweck C, Hill C, Horswill AR, Jaspars M, Kelly WL, Klinman JP, Kuipers OP, Link AJ, Liu W, Marahiel MA, Mitchell DA, Moll GN, Moore BS, Müller R, Nair SK, Nes IF, Norris GE, Olivera BM, Onaka H, Patchett ML, Piel J, Reaney MJ, Rebuffat S, Ross RP, Sahl HG, Schmidt EW, Selsted ME, Severinov K, Shen B, Sivonen K, Smith L, Stein T, Süssmuth RD, Tagg JR, Tang GL, Truman AW, Vederas JC, Walsh CT, Walton JD, Wenzel SC, Willey JM, van der Donk WA. Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Nat Prod Rep. 2012 Dec 10; 30(1):108-60.
-
Rath CM, Alexandrov T, Higginbottom SK, Song J, Milla ME, Fischbach MA, Sonnenburg JL, Dorrestein PC. Molecular analysis of model gut microbiotas by imaging mass spectrometry and nanodesorption electrospray ionization reveals dietary metabolite transformations. Anal Chem. 2012 Nov 6; 84(21):9259-67.
-
Holmes TC, May AE, Zaleta-Rivera K, Ruby JG, Skewes-Cox P, Fischbach MA, DeRisi JL, Iwatsuki M, Omura S, Khosla C. Molecular insights into the biosynthesis of guadinomine: a type III secretion system inhibitor. J Am Chem Soc. 2012 Oct 24; 134(42):17797-806.
-
Lemon KP, Armitage GC, Relman DA, Fischbach MA. Microbiota-targeted therapies: an ecological perspective. Sci Transl Med. 2012 Jun 6; 4(137):137rv5.
-
Gonzalez DJ, Xu Y, Yang YL, Esquenazi E, Liu WT, Edlund A, Duong T, Du L, Molnár I, Gerwick WH, Jensen PR, Fischbach M, Liaw CC, Straight P, Nizet V, Dorrestein PC. Observing the invisible through imaging mass spectrometry, a window into the metabolic exchange patterns of microbes. J Proteomics. 2012 Aug 30; 75(16):5069-76.
-
Fischbach MA, Sonnenburg JL. Eating for two: how metabolism establishes interspecies interactions in the gut. Cell Host Microbe. 2011 Oct 20; 10(4):336-47.
-
Assassi S, Leyva AL, Mayes MD, Sharif R, Nair DK, Fischbach M, Nguyen N, Reveille JD, Gonzalez EB, McNearney TA. Predictors of fatigue severity in early systemic sclerosis: a prospective longitudinal study of the GENISOS cohort. PLoS One. 2011; 6(10):e26061.
-
Kersten RD, Yang YL, Xu Y, Cimermancic P, Nam SJ, Fenical W, Fischbach MA, Moore BS, Dorrestein PC. A mass spectrometry-guided genome mining approach for natural product peptidogenomics. Nat Chem Biol. 2011 Nov; 7(11):794-802.
-
Fischbach MA. Combination therapies for combating antimicrobial resistance. Curr Opin Microbiol. 2011 Oct; 14(5):519-23.
-
Medema MH, Blin K, Cimermancic P, de Jager V, Zakrzewski P, Fischbach MA, Weber T, Takano E, Breitling R. antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences. Nucleic Acids Res. 2011 Jul; 39(Web Server issue):W339-46.
-
Sonnenburg JL, Fischbach MA. Community health care: therapeutic opportunities in the human microbiome. Sci Transl Med. 2011 Apr 13; 3(78):78ps12.
-
Fischbach M, Voigt CA. Prokaryotic gene clusters: a rich toolbox for synthetic biology. Biotechnol J. 2010 Dec; 5(12):1277-96.
-
Song JY, Jeong H, Yu DS, Fischbach MA, Park HS, Kim JJ, Seo JS, Jensen SE, Oh TK, Lee KJ, Kim JF. Draft genome sequence of Streptomyces clavuligerus NRRL 3585, a producer of diverse secondary metabolites. J Bacteriol. 2010 Dec; 192(23):6317-8.
-
Zimmermann M, Fischbach MA. A family of pyrazinone natural products from a conserved nonribosomal peptide synthetase in Staphylococcus aureus. Chem Biol. 2010 Sep 24; 17(9):925-30.
-
Fischbach MA, Krogan NJ. The next frontier of systems biology: higher-order and interspecies interactions. Genome Biol. 2010; 11(5):208.
-
Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F, Maheswaran S, McDermott U, Azizian N, Zou L, Fischbach MA, Wong KK, Brandstetter K, Wittner B, Ramaswamy S, Classon M, Settleman J. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell. 2010 Apr 2; 141(1):69-80.
-
Dawlaty J, Zhang X, Fischbach MA, Clardy J. Dapdiamides, tripeptide antibiotics formed by unconventional amide ligases. J Nat Prod. 2010 Mar 26; 73(3):441-6.
-
Walsh CT, Fischbach MA. Natural products version 2.0: connecting genes to molecules. J Am Chem Soc. 2010 Mar 3; 132(8):2469-93.
-
Haas BJ, Kamoun S, Zody MC, Jiang RH, Handsaker RE, Cano LM, Grabherr M, Kodira CD, Raffaele S, Torto-Alalibo T, Bozkurt TO, Ah-Fong AM, Alvarado L, Anderson VL, Armstrong MR, Avrova A, Baxter L, Beynon J, Boevink PC, Bollmann SR, Bos JI, Bulone V, Cai G, Cakir C, Carrington JC, Chawner M, Conti L, Costanzo S, Ewan R, Fahlgren N, Fischbach MA, Fugelstad J, Gilroy EM, Gnerre S, Green PJ, Grenville-Briggs LJ, Griffith J, Grünwald NJ, Horn K, Horner NR, Hu CH, Huitema E, Jeong DH, Jones AM, Jones JD, Jones RW, Karlsson EK, Kunjeti SG, Lamour K, Liu Z, Ma L, Maclean D, Chibucos MC, McDonald H, McWalters J, Meijer HJ, Morgan W, Morris PF, Munro CA, O'Neill K, Ospina-Giraldo M, Pinzón A, Pritchard L, Ramsahoye B, Ren Q, Restrepo S, Roy S, Sadanandom A, Savidor A, Schornack S, Schwartz DC, Schumann UD, Schwessinger B, Seyer L, Sharpe T, Silvar C, Song J, Studholme DJ, Sykes S, Thines M, van de Vondervoort PJ, Phuntumart V, Wawra S, Weide R, Win J, Young C, Zhou S, Fry W, Meyers BC, van West P, Ristaino J, Govers F, Birch PR, Whisson SC, Judelson HS, Nusbaum C. Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans. Nature. 2009 Sep 17; 461(7262):393-8.
-
Fischbach MA, Walsh CT. Antibiotics for emerging pathogens. Science. 2009 Aug 28; 325(5944):1089-93.
-
Fischbach MA. Antibiotics from microbes: converging to kill. Curr Opin Microbiol. 2009 Oct; 12(5):520-7.
-
Walsh CT, Fischbach MA. New ways to squash superbugs. Sci Am. 2009 Jul; 301(1):44-51.
-
Clardy J, Fischbach MA, Currie CR. The natural history of antibiotics. Curr Biol. 2009 Jun 9; 19(11):R437-41.
-
Wieland Brown LC, Acker MG, Clardy J, Walsh CT, Fischbach MA. Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin. Proc Natl Acad Sci U S A. 2009 Feb 24; 106(8):2549-53.
-
Walsh CT, Fischbach MA. Repurposing libraries of eukaryotic protein kinase inhibitors for antibiotic discovery. Proc Natl Acad Sci U S A. 2009 Feb 10; 106(6):1689-90.
-
López D, Fischbach MA, Chu F, Losick R, Kolter R. Structurally diverse natural products that cause potassium leakage trigger multicellularity in Bacillus subtilis. Proc Natl Acad Sci U S A. 2009 Jan 6; 106(1):280-5.
-
Sattely ES, Fischbach MA, Walsh CT. Total biosynthesis: in vitro reconstitution of polyketide and nonribosomal peptide pathways. Nat Prod Rep. 2008 Aug; 25(4):757-93.
-
Stinear TP, Seemann T, Harrison PF, Jenkin GA, Davies JK, Johnson PD, Abdellah Z, Arrowsmith C, Chillingworth T, Churcher C, Clarke K, Cronin A, Davis P, Goodhead I, Holroyd N, Jagels K, Lord A, Moule S, Mungall K, Norbertczak H, Quail MA, Rabbinowitsch E, Walker D, White B, Whitehead S, Small PL, Brosch R, Ramakrishnan L, Fischbach MA, Parkhill J, Cole ST. Insights from the complete genome sequence of Mycobacterium marinum on the evolution of Mycobacterium tuberculosis. Genome Res. 2008 May; 18(5):729-41.
-
Fischbach MA, Walsh CT, Clardy J. The evolution of gene collectives: How natural selection drives chemical innovation. Proc Natl Acad Sci U S A. 2008 Mar 25; 105(12):4601-8.
-
Walsh CT, Fischbach MA. Inhibitors of sterol biosynthesis as Staphylococcus aureus antibiotics. Angew Chem Int Ed Engl. 2008; 47(31):5700-2.
-
Nolan EM, Fischbach MA, Koglin A, Walsh CT. Biosynthetic tailoring of microcin E492m: post-translational modification affords an antibacterial siderophore-peptide conjugate. J Am Chem Soc. 2007 Nov 21; 129(46):14336-47.
-
Fischbach MA, Lai JR, Roche ED, Walsh CT, Liu DR. Directed evolution can rapidly improve the activity of chimeric assembly-line enzymes. Proc Natl Acad Sci U S A. 2007 Jul 17; 104(29):11951-6.
-
Fischbach MA, Clardy J. One pathway, many products. Nat Chem Biol. 2007 Jul; 3(7):353-5.
-
Butcher RA, Schroeder FC, Fischbach MA, Straight PD, Kolter R, Walsh CT, Clardy J. The identification of bacillaene, the product of the PksX megacomplex in Bacillus subtilis. Proc Natl Acad Sci U S A. 2007 Jan 30; 104(5):1506-9.
-
Straight PD, Fischbach MA, Walsh CT, Rudner DZ, Kolter R. A singular enzymatic megacomplex from Bacillus subtilis. Proc Natl Acad Sci U S A. 2007 Jan 2; 104(1):305-10.
-
Clardy J, Fischbach MA, Walsh CT. New antibiotics from bacterial natural products. Nat Biotechnol. 2006 Dec; 24(12):1541-50.
-
Fischbach MA, Walsh CT. Biochemistry. Directing biosynthesis. Science. 2006 Oct 27; 314(5799):603-5.
-
Fischbach MA, Lin H, Zhou L, Yu Y, Abergel RJ, Liu DR, Raymond KN, Wanner BL, Strong RK, Walsh CT, Aderem A, Smith KD. The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2. Proc Natl Acad Sci U S A. 2006 Oct 31; 103(44):16502-7.
-
Lai JR, Fischbach MA, Liu DR, Walsh CT. Localized protein interaction surfaces on the EntB carrier protein revealed by combinatorial mutagenesis and selection. J Am Chem Soc. 2006 Aug 30; 128(34):11002-3.
-
Larsen NA, Lin H, Wei R, Fischbach MA, Walsh CT. Structural characterization of enterobactin hydrolase IroE. Biochemistry. 2006 Aug 29; 45(34):10184-90.
-
Jin M, Fischbach MA, Clardy J. A biosynthetic gene cluster for the acetyl-CoA carboxylase inhibitor andrimid. J Am Chem Soc. 2006 Aug 23; 128(33):10660-1.
-
Fischbach MA, Walsh CT. Assembly-line enzymology for polyketide and nonribosomal Peptide antibiotics: logic, machinery, and mechanisms. Chem Rev. 2006 Aug; 106(8):3468-96.
-
Lin H, Fischbach MA, Gatto GJ, Liu DR, Walsh CT. Bromoenterobactins as potent inhibitors of a pathogen-associated, siderophore-modifying C-glycosyltransferase. J Am Chem Soc. 2006 Jul 26; 128(29):9324-5.
-
Sharma SV, Fischbach MA, Haber DA, Settleman J. "Oncogenic shock": explaining oncogene addiction through differential signal attenuation. Clin Cancer Res. 2006 Jul 15; 12(14 Pt 2):4392s-4395s.
-
Lai JR, Fischbach MA, Liu DR, Walsh CT. A protein interaction surface in nonribosomal peptide synthesis mapped by combinatorial mutagenesis and selection. Proc Natl Acad Sci U S A. 2006 Apr 4; 103(14):5314-9.
-
Fischbach MA, Lin H, Liu DR, Walsh CT. How pathogenic bacteria evade mammalian sabotage in the battle for iron. Nat Chem Biol. 2006 Mar; 2(3):132-8.
-
Luo M, Lin H, Fischbach MA, Liu DR, Walsh CT, Groves JT. Enzymatic tailoring of enterobactin alters membrane partitioning and iron acquisition. ACS Chem Biol. 2006 Feb 17; 1(1):29-32.
-
Dorrestein PC, Blackhall J, Straight PD, Fischbach MA, Garneau-Tsodikova S, Edwards DJ, McLaughlin S, Lin M, Gerwick WH, Kolter R, Walsh CT, Kelleher NL. Activity screening of carrier domains within nonribosomal peptide synthetases using complex substrate mixtures and large molecule mass spectrometry. Biochemistry. 2006 Feb 14; 45(6):1537-46.
-
Fischbach MA, Settleman J. Regulation of the nucleotide state of oncogenic ras proteins by nucleoside diphosphate kinase. Methods Enzymol. 2006; 407:33-45.
-
Garstecki P, J Fuerstman M, Fischbach MA, Sia SK, Whitesides GM. Mixing with bubbles: a practical technology for use with portable microfluidic devices. Lab Chip. 2006 Feb; 6(2):207-12.
-
Lin H, Fischbach MA, Liu DR, Walsh CT. In vitro characterization of salmochelin and enterobactin trilactone hydrolases IroD, IroE, and Fes. J Am Chem Soc. 2005 Aug 10; 127(31):11075-84.
-
Fischbach MA, Lin H, Liu DR, Walsh CT. In vitro characterization of IroB, a pathogen-associated C-glycosyltransferase. Proc Natl Acad Sci U S A. 2005 Jan 18; 102(3):571-6.
-
Wolfe DB, Conroy RS, Garstecki P, Mayers BT, Fischbach MA, Paul KE, Prentiss M, Whitesides GM. Dynamic control of liquid-core/liquid-cladding optical waveguides. Proc Natl Acad Sci U S A. 2004 Aug 24; 101(34):12434-8.
-
Fischbach MA, Settleman J. Specific biochemical inactivation of oncogenic Ras proteins by nucleoside diphosphate kinase. Cancer Res. 2003 Jul 15; 63(14):4089-94.
|
Michael's Networks
Click the "See All" links for more information and interactive visualizations!
Related Concepts Derived automatically from this person's publications. _
Co-Authors People in Profiles who have published with this person. _
Related Authors People who share similar concepts with this person. _
|
