- Assistant Professor, San Diego State University, 2017-present
- Post-doctoral Fellow, The Scripps Research Institute, 2015-2017
- Ph.D. Chemical Biology, McMaster University, 2015
- B.Sc. Chemistry, summa cum laude, McMaster University, 2008
Have you ever had a gut feeling?
Well, there may be a scientific explanation to this phenomenon! Within the last
decade, there has been a significant paradigm shift in our understanding of the
human microbiome and its impact on human health. Microbial cells outnumber
human cells 10 to 1, and we have only recently begun to understand their impact
on producing metabolites that affect us. One uncharacterized interaction is the
interface between microbial metabolites and neurological function, or the
gut-brain axis. Gut metabolites, such as serotonin, impact our feelings of
hunger and satiety, but can play a major role in diseases such as irritable
bowel syndrome, obesity, and colon cancer, and even anxiety and
Culturing Anaerobic Microorganisms in a Human Gut Model
The Forsberg lab looks to
decipher biological mechanisms of gut microbiota using analytical techniques,
particularly mass spectrometry (MS) based metabolomics. A key to understanding
mechanistic perturbations in a biological system requires growing anaerobic
bacteria in a system closely resembling the human gut. Anaerobic culturing
techniques facilitate growth studies looking at the effects that diet,
antibiotics and xenobiotics have on microbial growth, metabolism and signaling.
Culturing gut microorganisms is challenging. Mimicking conditions inside the
human intestinal tract has yet to be perfected in the laboratory setting, and
metabolite extraction methods need further development.
Gut microbe culturing and analysis workflow
requires optimization of anaerobic conditions, the addition of a stress
condition, such as antibiotics, for comparison, metabolite extraction followed
by liquid chromatography high resolution mass spectrometry (LC-HRMS).
Metabolomics and Bioinformatics
Metabolomics focuses on bioactive
small molecules, such as central carbon metabolites involved in biosynthetic
pathways. When a well-characterized biological system is stressed, metabolites
may become dysregulated. We can analyze these alterations in metabolic pathways
via tandem mass spectrometry, which fragments analytes and tracks specific
product ions. Quantifying metabolite changes can illuminate alterations in
protein activity stemming from inhibition, activation, or changes in regulation.
When the stress effects are unknown or the pathways are uncharacterized,
microbial metabolism is far more complicated and requires global or untargeted
metabolomics, which profiles the entire metabolome in an unbiased manner.
However, the complexity of samples results in tens of thousands of detected metabolites
and requires intense data analysis using bioinformatics. Although there are some
excellent platforms available for analyzing untargeted data (e.g. MetaboScape,
XCMS Online, MetaboAnalyst), they have their limits. There is still a need to
improve data integration and statistical methods from multiple organisms. Our
goal is to effectively understand interactions between multiple microbial
sources, or microbiota and human host, in a single streamlined analysis.
Example of bioinformatic analysis workflow
for large untargeted metabolomic datasets in conjunction with multi-omics data
using XCMS Online. These powerful tools will help us build a system to analyze
multiple microorganisms and the human host simultaneously.
Separation and Identification of Complex Biological Mixtures
High resolution (HR) instruments
such as quadrupole time of flight (QTOF) or Orbitrap mass spectrometers
accurately and precisely measure a large dynamic range of molecular weight
analytes, from small molecules to large proteins. Our lab utilizes HR-MS
coupled to liquid chromatography (LC) to identify compounds in complex
biological mixtures. LC provides a means to separate a biological sample to
achieve high metabolomic coverage over both hydrophobic and polar compounds.
Although LC powerfully separates a large range of analytes without modifying
the sample, it is less reproducible and slower than gas chromatography (GC). We
will develop novel methods employing a wide variety of stationary phases and
sample introduction techniques to maximize efficiency and reproducibility of
separations at low cost.
PubMed list of
- Forsberg, E.; Huan, T.;
Rinehart, D.; Benton, H. P.; Hilmers, B.; Warth, B.; Siuzdak, G.,
XCMS Online Data Processing, Pathway Mapping and Multi-Omic Systems Analysis.
Nature Protocols 2018 13, 633-651
- Huan, T.; Forsberg, E.
M.; Rinehart, D.; Johnson, C. H.; Ivanisevic, J.; Benton, H. P.; Fang, M.;
Aisporna, A.; Hilmers, B.; Poole, F. L.; Thorgersen, M. P.; Adams, M. W. W.;
Krantz, G.; Fields, M. W.; Robbins, P. D.; Niedernhofer, L. J.; Ideker, T.; Majumder,
E. L.; Wall, J. D.; Rattray, N. J. W.; Goodacre, R.; Lairson, L. L.; Siuzdak,
G., Systems biology guided by XCMS Online metabolomics. Nat Meth 2017,
14 (5), 461-462.
- Gendelman, H. E.; Zhang,
Y.; Santamaria, P.; Olson, K. E.; Schutt, C. R.; Bhatti, D.; Shetty, B. L. D.;
Lu, Y.; Estes, K. A.; Standaert, D. G.; Heinrichs-Graham, E.; Larson, L.; Meza,
J. L.; Follett, M.; Forsberg, E.; Siuzdak, G.; Wilson, T. W.; Peterson, C.;
Mosley, R. L., Evaluation of the safety and immunomodulatory effects of sargramostim
in a randomized, double-blind phase 1 clinical Parkinsons disease trial. npj
Parkinson's Disease 2017, 3 (1), 10.
- Forsberg, E.; Fang, M.;
Siuzdak, G., Staying Alive: Measuring Intact Viable Microbes with Electrospray
Ionization Mass Spectrometry. Journal of The American Society for Mass
Spectrometry 2017, 28 (1), 14-20.
- Kurczy, M. E.; Forsberg,
E. M.; Thorgersen, M. P.; Poole, F. L.; Benton, H. P.; Ivanisevic, J.; Tran, M.
L.; Wall, J. D.; Elias, D. A.; Adams, M. W. W.; Siuzdak, G., Global Isotope
Metabolomics Reveals Adaptive Strategies for Nitrogen Assimilation. ACS
Chemical Biology 2016, 11 (6), 1677-1685.
- Forsberg, E. M.; Sicard,
C.; Brennan, J. D., Solid-Phase Biological Assays for Drug Discovery. Annual
Review of Analytical Chemistry 2014, 7 (1), 337-359.
- Forsberg, E. M.;
Brennan, J. D., Bio-Solid-Phase Extraction/Tandem Mass Spectrometry for
Identification of Bioactive Compounds in Mixtures. Analytical Chemistry 2014,
86 (16), 8457-8465.
- Forsberg, E. M.; Green,
J. R. A.; Brennan, J. D., Continuous Flow Immobilized Enzyme Reactor-Tandem
Mass Spectrometry for Screening of AChE Inhibitors in Complex Mixtures. Analytical
Chemistry 2011, 83 (13), 5230-5236.