Michael Fischbach

Last updated
Michael Fischbach
Born(1980-11-03)November 3, 1980
Alma mater
Spouse Elizabeth Sattely
Awards National Institutes of Health Director's Pioneer Award

HHMI-Simons Faculty Scholars Award

Chan Zuckerberg Biohub investigator
Scientific career
Institutions
Thesis Nonribosomal peptide biosynthesis: Directed evolution of assembly line enzymes and characterization of post-assembly line tailoring  (2007)
Doctoral advisor Christopher Walsh
Notable studentsYiYin Erin Chen
Website fischbachgroup.org

Michael Andrew Fischbach (born November 3, 1980) is an American chemist, microbiologist, and geneticist. He is an associate professor of Bioengineering and ChEM-H Faculty Fellow at Stanford University [1] [2] and a Chan Zuckerberg Biohub Investigator. [3]

Contents

Education

Fischbach earned his A.B. in Biochemical Sciences from Harvard College in 2003. During that time (2000-2003), he worked in Jeffrey Settleman's lab at the Massachusetts General Hospital Cancer Center on the biochemistry of oncogenic mutants of the small GTPase Ras. [4] In 2007, he earned his Ph.D. in Chemistry and Chemical Biology from Harvard University, working in Christopher T. Walsh's laboratory at Harvard Medical School on iron acquisition in bacterial pathogens and the biochemistry of natural product biosynthesis. [5] [6]

Career

Fischbach was a junior fellow in the Department of Molecular Biology at Massachusetts General Hospital (2007-2009) before joining the faculty of the University of California, San Francisco in 2009. He moved to Stanford University as an associate professor in September 2017. As a Chan Zuckerberg Biohub Investigator, Fischbach is one of eight faculty members across Stanford, UCSF, and the University of California, Berkeley leading the CZ Biohub Microbiome Initiative, launched in 2018, with the goal of understanding how the microbiota can influence human health. [7]

Fischbach is currently a member of the scientific advisory board of NGM Biopharmaceuticals [8] and a co-founder of Revolution Medicines. [9]

Research

Fischbach's lab focuses on discovering and characterizing small molecules from microorganisms, with an emphasis on the human microbiome. [10] [11]

Small molecules from the human microbiota

In 2014, Fischbach and his laboratory published a survey of biosynthetic genes in the human microbiome, describing the ability of human-associated microbes to produce thiopeptide antibiotics. [12] [13] [14] [15] The Fischbach lab discovered that the gut commensal Bacteroides fragilis produces the immune modulatory sphingolipid alpha-galactosylceramide, [16] showed that the production of neurotransmitters is common among commensal gut bacteria, [17] and discovered the biosynthetic pathway for a common class of bile acids produced by gut bacteria. [18]

Computational approaches to natural product discovery

Fischbach's lab developed an algorithm, ClusterFinder, that automates the process of identifying biosynthetic genes for small molecules in bacterial genome sequences. [19] [20] With Marnix Medema, he co-developed a second algorithm for identifying biosynthetic gene clusters, antiSMASH, [21] with which ClusterFinder has been merged.

Engineered Bacteria Theraputics

Fischbach's team has made significant strides in engineering commensal bacteria for therapeutic purposes. They transformed the ubiquitous skin bacterium Staphylococcus epidermidis into a topical vaccine platform. [22] [23] This approach generated potent, durable, and specific antibody responses in mice, potentially offering a new method for vaccine delivery. [24] In 2023, his postdoc Erin Chen led an effort to engineer skin bacteria to induce antitumor T cell responses against melanoma, highlighting the potential of the skin microbiome in cancer immunotherapy. [25] [26]

Personal life

Fischbach is married to Elizabeth Sattely, Associate Professor of Chemical Engineering at Stanford. [27]

Related Research Articles

<span class="mw-page-title-main">Human microbiome</span> Microorganisms in or on human skin and biofluids

The human microbiome is the aggregate of all microbiota that reside on or within human tissues and biofluids along with the corresponding anatomical sites in which they reside, including the gastrointestinal tract, skin, mammary glands, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, conjunctiva, and the biliary tract. Types of human microbiota include bacteria, archaea, fungi, protists, and viruses. Though micro-animals can also live on the human body, they are typically excluded from this definition. In the context of genomics, the term human microbiome is sometimes used to refer to the collective genomes of resident microorganisms; however, the term human metagenome has the same meaning.

Computational genomics refers to the use of computational and statistical analysis to decipher biology from genome sequences and related data, including both DNA and RNA sequence as well as other "post-genomic" data. These, in combination with computational and statistical approaches to understanding the function of the genes and statistical association analysis, this field is also often referred to as Computational and Statistical Genetics/genomics. As such, computational genomics may be regarded as a subset of bioinformatics and computational biology, but with a focus on using whole genomes to understand the principles of how the DNA of a species controls its biology at the molecular level and beyond. With the current abundance of massive biological datasets, computational studies have become one of the most important means to biological discovery.

<span class="mw-page-title-main">Gut microbiota</span> Community of microorganisms in the gut

Gut microbiota, gut microbiome, or gut flora are the microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut microbiota. The gut is the main location of the human microbiome. The gut microbiota has broad impacts, including effects on colonization, resistance to pathogens, maintaining the intestinal epithelium, metabolizing dietary and pharmaceutical compounds, controlling immune function, and even behavior through the gut–brain axis.

Dysbiosis is characterized by a disruption to the microbiome resulting in an imbalance in the microbiota, changes in their functional composition and metabolic activities, or a shift in their local distribution. For example, a part of the human microbiota such as the skin flora, gut flora, or vaginal flora, can become deranged (unbalanced), when normally dominating species become underrepresented and species that normally are outcompeted or contained increase to fill the void. Similar to the human gut microbiome, diverse microbes colonize the plant rhizosphere, and dysbiosis in the rhizosphere, can negatively impact plant health. Dysbiosis is most commonly reported as a condition in the gastrointestinal tract or plant rhizosphere.

<span class="mw-page-title-main">Skin flora</span> Microbiota that reside on the skin

Skin flora, also called skin microbiota, refers to microbiota that reside on the skin, typically human skin.

<span class="mw-page-title-main">Human Microbiome Project</span> Former research initiative

The Human Microbiome Project (HMP) was a United States National Institutes of Health (NIH) research initiative to improve understanding of the microbiota involved in human health and disease. Launched in 2007, the first phase (HMP1) focused on identifying and characterizing human microbiota. The second phase, known as the Integrative Human Microbiome Project (iHMP) launched in 2014 with the aim of generating resources to characterize the microbiome and elucidating the roles of microbes in health and disease states. The program received $170 million in funding by the NIH Common Fund from 2007 to 2016.

<span class="mw-page-title-main">Microbial symbiosis and immunity</span>

Long-term close-knit interactions between symbiotic microbes and their host can alter host immune system responses to other microorganisms, including pathogens, and are required to maintain proper homeostasis. The immune system is a host defense system consisting of anatomical physical barriers as well as physiological and cellular responses, which protect the host against harmful microorganisms while limiting host responses to harmless symbionts. Humans are home to 1013 to 1014 bacteria, roughly equivalent to the number of human cells, and while these bacteria can be pathogenic to their host most of them are mutually beneficial to both the host and bacteria.

<span class="mw-page-title-main">Microbiota</span> Community of microorganisms

Microbiota are the range of microorganisms that may be commensal, mutualistic, or pathogenic found in and on all multicellular organisms, including plants. Microbiota include bacteria, archaea, protists, fungi, and viruses, and have been found to be crucial for immunologic, hormonal, and metabolic homeostasis of their host.

The lung microbiota is the pulmonary microbial community consisting of a complex variety of microorganisms found in the lower respiratory tract particularly on the mucous layer and the epithelial surfaces. These microorganisms include bacteria, fungi, viruses and bacteriophages. The bacterial part of the microbiota has been more closely studied. It consists of a core of nine genera: Prevotella, Sphingomonas, Pseudomonas, Acinetobacter, Fusobacterium, Megasphaera, Veillonella, Staphylococcus, and Streptococcus. They are aerobes as well as anaerobes and aerotolerant bacteria. The microbial communities are highly variable in particular individuals and compose of about 140 distinct families. The bronchial tree for instance contains a mean of 2000 bacterial genomes per cm2 surface. The harmful or potentially harmful bacteria are also detected routinely in respiratory specimens. The most significant are Moraxella catarrhalis, Haemophilus influenzae, and Streptococcus pneumoniae. They are known to cause respiratory disorders under particular conditions namely if the human immune system is impaired. The mechanism by which they persist in the lower airways in healthy individuals is unknown.

Skin immunity is a property of skin that allows it to resist infections from pathogens. In addition to providing a passive physical barrier against infection, the skin also contains elements of the innate and adaptive immune systems which allows it to actively fight infections. Hence the skin provides defense in depth against infection.

<span class="mw-page-title-main">Gut–brain axis</span> Biochemical signaling between the gastrointestinal tract and the central nervous system

The gut–brain axis is the two-way biochemical signaling that takes place between the gastrointestinal tract and the central nervous system (CNS). The term "microbiota–gut–brain axis" highlights the role of gut microbiota in these biochemical signaling. Broadly defined, the gut–brain axis includes the central nervous system, neuroendocrine system, neuroimmune systems, the hypothalamic–pituitary–adrenal axis, sympathetic and parasympathetic arms of the autonomic nervous system, the enteric nervous system, vagus nerve, and the gut microbiota.

Microbiota-accessible carbohydrates (MACs) are carbohydrates that are resistant to digestion by a host's metabolism, and are made available for gut microbes, as prebiotics, to ferment or metabolize into beneficial compounds, such as short chain fatty acids. The term, ‘‘microbiota-accessible carbohydrate’’ contributes to a conceptual framework for investigating and discussing the amount of metabolic activity that a specific food or carbohydrate can contribute to a host's microbiota.

<span class="mw-page-title-main">Lactocillin</span> Chemical compound

Lactocillin is a thiopeptide antibiotic which is encoded for and produced by biosynthetic genes clusters in the bacteria Lactobacillus gasseri. Lactocillin was discovered and purified in 2014. Lactobacillus gasseri is one of the four Lactobacillus bacteria found to be most common in the human vaginal microbiome. Due to increasing levels of pathogenic resistance to known antibiotics, novel antibiotics are increasingly valuable. Lactocillin could function as a new antibiotic that could help people fight off infections that are resistant to many other antibiotics.

<span class="mw-page-title-main">Microbiome</span> Microbial community assemblage and activity

A microbiome is the community of microorganisms that can usually be found living together in any given habitat. It was defined more precisely in 1988 by Whipps et al. as "a characteristic microbial community occupying a reasonably well-defined habitat which has distinct physio-chemical properties. The term thus not only refers to the microorganisms involved but also encompasses their theatre of activity". In 2020, an international panel of experts published the outcome of their discussions on the definition of the microbiome. They proposed a definition of the microbiome based on a revival of the "compact, clear, and comprehensive description of the term" as originally provided by Whipps et al., but supplemented with two explanatory paragraphs, the first pronouncing the dynamic character of the microbiome, and the second clearly separating the term microbiota from the term microbiome.

The microbiota are the sum of all symbiotic microorganisms living on or in an organism. The fruit fly Drosophila melanogaster is a model organism and known as one of the most investigated organisms worldwide. The microbiota in flies is less complex than that found in humans. It still has an influence on the fitness of the fly, and it affects different life-history characteristics such as lifespan, resistance against pathogens (immunity) and metabolic processes (digestion). Considering the comprehensive toolkit available for research in Drosophila, analysis of its microbiome could enhance our understanding of similar processes in other types of host-microbiota interactions, including those involving humans. Microbiota plays key roles in the intestinal immune and metabolic responses via their fermentation product, acetate.

<span class="mw-page-title-main">Uterine microbiome</span>

The uterine microbiome refers to the community of commensal, nonpathogenic microorganisms—including bacteria, viruses, and yeasts/fungi—present in a healthy uterus, as well as in the amniotic fluid and endometrium. These microorganisms coexist in a specific environment within the uterus, playing a vital role in maintaining reproductive health. In the past, the uterus was believed to be a sterile environment, free of any microbial life. Recent advancements in microbiological research, particularly the improvement of 16S rRNA gene sequencing techniques, have challenged this long-held belief. These advanced techniques have made it possible to detect bacteria and other microorganisms present in very low numbers. Using this procedure that allows the detection of bacteria that cannot be cultured outside the body, studies of microbiota present in the uterus are expected to increase.

<span class="mw-page-title-main">Pharmacomicrobiomics</span>

Pharmacomicrobiomics, proposed by Prof. Marco Candela for the ERC-2009-StG project call, and publicly coined for the first time in 2010 by Rizkallah et al., is defined as the effect of microbiome variations on drug disposition, action, and toxicity. Pharmacomicrobiomics is concerned with the interaction between xenobiotics, or foreign compounds, and the gut microbiome. It is estimated that over 100 trillion prokaryotes representing more than 1000 species reside in the gut. Within the gut, microbes help modulate developmental, immunological and nutrition host functions. The aggregate genome of microbes extends the metabolic capabilities of humans, allowing them to capture nutrients from diverse sources. Namely, through the secretion of enzymes that assist in the metabolism of chemicals foreign to the body, modification of liver and intestinal enzymes, and modulation of the expression of human metabolic genes, microbes can significantly impact the ingestion of xenobiotics.

Metabolic gene clusters or biosynthetic gene clusters are tightly linked sets of mostly non-homologous genes participating in a common, discrete metabolic pathway. The genes are in physical vicinity to each other on the genome, and their expression is often coregulated. Metabolic gene clusters are common features of bacterial and most fungal genomes. They are less often found in other organisms. They are most widely known for producing secondary metabolites, the source or basis of most pharmaceutical compounds, natural toxins, chemical communication, and chemical warfare between organisms. Metabolic gene clusters are also involved in nutrient acquisition, toxin degradation, antimicrobial resistance, and vitamin biosynthesis. Given all these properties of metabolic gene clusters, they play a key role in shaping microbial ecosystems, including microbiome-host interactions. Thus several computational genomics tools have been developed to predict metabolic gene clusters.

<i>Bacteroides thetaiotaomicron</i> Species of bacterium

Bacteroides thetaiotaomicron is a Gram-negative, obligate anaerobic bacterium and a prominent member of the human gut microbiota, particularly within the large intestine. B. thetaiotaomicron belongs to the Bacteroides genus – a group that is known for its role in the complex microbial community of the gut microbiota. Its proteome, consisting of 4,779 members, includes a system for obtaining and breaking down dietary polysaccharides that would otherwise be difficult to digest for the human body.

<span class="mw-page-title-main">Yasmine Belkaid</span> Algerian immunologist

Yasmine Belkaid is an Algerian immunologist who is best known for her work studying host-microbe interactions in tissues and immune regulation to microbes. Belkaid currently serves as the director of the NIAID Microbiome program. On March 29, 2023, she was appointed as President of the Pasteur Institute for a six-year term, starting from January 2024.

References

  1. ↑ "Michael Fischbach's Profile | Stanford Profiles". profiles.stanford.edu. Retrieved 2019-07-12.
  2. ↑ "Faculty Fellows | ChEM-H". chemh.stanford.edu. Retrieved 2019-07-12.
  3. ↑ "Investigator Program – Chan Zuckerberg Biohub" . Retrieved 2019-07-12.
  4. ↑ Fischbach MA, Settleman J. Specific biochemical inactivation of oncogenic Ras proteins by nucleoside diphosphate kinase. Cancer Res. 2003 Jul 15;63(14):4089-94. PMID   12874011.
  5. ↑ 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. Epub 2004 Dec 14. PMID   15598734; PMC   545562.
  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. doi : 10.1021/ja909118a. PMID   20121095; PMC   2828520.
  7. ↑ "Chan Zuckerberg Biohub funds new research efforts, microbiome initiative". News Center. 8 February 2017. Retrieved 2019-07-12.
  8. ↑ "Scientific Advisory Board - NGM Bio". www.ngmbio.com. Archived from the original on 2018-07-20. Retrieved 2016-01-07.
  9. ↑ "Team - Revolution Medicines". revolutionmedicines.com.
  10. ↑ "Fischbach Group - Home". fischbachgroup.org.
  11. ↑ Donia MS, Fischbach MA. Small molecules from the human microbiota. Science. 2015 Jul 24;349(6246):1254766. doi : 10.1126/science.1254766. Epub 2015 Jul 23. Review. PMID   26206939; PMC   4641445
  12. ↑ Donia MS, Cimermancic P, Schulze CJ, Wieland Brown LC, Martin J, Mitreva M, Clardy J, Linington RG, Fischbach MA. A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics. Cell. 2014 Sep 11;158(6):1402-14. doi : 10.1016/j.cell.2014.08.032. PMID   25215495; PMC   4164201.
  13. ↑ "Mining for Antibiotics, Right Under Our Noses". The New York Times. 2014-09-11.
  14. ↑ Park, Alice (2014-09-12). "DIY Drugs: Antibiotics Could Soon Be Made Out of Your Own Bacteria". Time. Retrieved 2018-04-26.
  15. ↑ "Set a thief... Humanity's bacterial companions are a good place to look for new drugs". The Economist. 2014-09-20. Retrieved 2018-04-26.
  16. ↑ Wieland Brown LC, Penaranda C, Kashyap PC, Williams BB, Clardy J, Kronenberg M, Sonnenburg JL, Comstock LE, Bluestone JA, Fischbach MA. Production of α-galactosylceramide by a prominent member of the human gut microbiota. PLoS Biol. 2013 Jul;11(7):e1001610. doi : 10.1371/journal.pbio.1001610. Epub 2013 Jul 16. PMID   23874157; PMC   3712910.
  17. ↑ Williams BB, Van Benschoten AH, Cimermancic P, Donia MS, Zimmermann M, Taketani M, Ishihara A, Kashyap PC, Fraser JS, Fischbach MA. Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. Cell Host Microbe. 2014 Oct 8;16(4):495-503. doi : 10.1016/j.chom.2014.09.001. Epub 2014 Sep 25. PMID   25263219; PMC   4260654.
  18. ↑ Devlin AS, Fischbach MA. A biosynthetic pathway for a prominent class of microbiota-derived bile acids. Nat Chem Biol. 2015 Sep;11(9):685-90. doi : 10.1038/nchembio.1864. Epub 2015 Jul 20. PMID   26192599; PMC   4543561.
  19. ↑ Cimermancic P, Medema MH, Claesen J, Kurita K, Wieland Brown LC, Mavrommatis K, Pati A, Godfrey PA, Koehrsen M, Clardy J, Birren BW, Takano E, Sali A, Linington RG, Fischbach MA. Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters. Cell. 2014 Jul 17;158(2):412-21. doi : 10.1016/j.cell.2014.06.034. PMID   25036635; PMC   4123684.
  20. ↑ Medema MH, Fischbach MA. Computational approaches to natural product discovery. Nat Chem Biol. 2015 Sep;11(9):639-48. doi : 10.1038/nchembio.1884. PMID   26284671.
  21. ↑ "antiSMASH bacterial version". antismash.secondarymetabolites.org.
  22. ↑ Bousbaine, Djenet; Bauman, Katherine D.; Chen, Y. Erin; Lalgudi, Pranav V.; Nguyen, Tam T. D.; Swenson, Joyce M.; Yu, Victor K.; Tsang, Eunice; Conlan, Sean; Li, David B.; Jbara, Amina; Zhao, Aishan; Naziripour, Arash; Veinbachs, Alessandra; Lee, Yu E. (2024-12-11). "Discovery and engineering of the antibody response to a prominent skin commensal". Nature: 1–3. doi:10.1038/s41586-024-08489-4. ISSN   1476-4687.
  23. ↑ "Stanford scientists transform ubiquitous skin bacterium into a topical vaccine". med.stanford.edu. Retrieved 2025-01-21.
  24. ↑ Lee, Jeong-Mi; Sage, Peter T. (2024-12-19). "Skin in the game — locally made antibodies fight resident bacteria". Nature. doi:10.1038/d41586-024-04205-4. ISSN   1476-4687.
  25. ↑ Chen, Y. Erin; Bousbaine, Djenet; Veinbachs, Alessandra; Atabakhsh, Katayoon; Dimas, Alex; Yu, Victor K.; Zhao, Aishan; Enright, Nora J.; Nagashima, Kazuki; Belkaid, Yasmine; Fischbach, Michael A. (2023-04-14). "Engineered skin bacteria induce antitumor T cell responses against melanoma". Science. 380 (6641): 203–210. doi:10.1126/science.abp9563.
  26. ↑ "Researchers use skin-colonizing bacteria to create a topical cancer therapy in mice". News Center. Retrieved 2025-01-21.
  27. ↑ "Elizabeth Sattely's Profile | Stanford Profiles". profiles.stanford.edu. Retrieved 2019-07-12.
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