Research
The Nemet lab focuses on understanding the communication between gut microorganisms and their host. In particular, how microbial metabolic pathways contribute to overall changes in host physiology, and cardiometabolic disease susceptibility. The laboratory works on identifying novel pathways of clinical relevance with mechanistic links to human diseases by use of metabolomics (mass spectrometry) and clinical studies in tandem with mechanistic studies.
Biography
Dr. Ina Nemet received her bachelor degree in biochemical engineering at the University of Zagreb, Croatia followed by a masters degree and PhD in organic chemistry at the same university. Dr. Nemet received her postdoctoral training at Case Western Reserve University (CWRU) in Cleveland, Ohio in the Departments of Pathology where she worked on identifing pathways that lead to the accumulation of reactive α-oxoaldehydes and their contribution to health decline in ageing and diabetes. This was followed by her second postdoctoral training in the Department of Pahrmacology at CWRU where she worked on clarifying the mechanism of the photoreceptor outer membrane morphogenesis by employing novel fluorescence imaging techniques. During her training Dr. Nemet received Fulbright Visiting Research Fellowship and Juvenile Diabetes Research International Postdoctoral Fellowship.
After joining Hazen Lab as a junior faculty, Dr. Nemet spearheaded a multidisciplinary study that began with large-scale clinical association studies and resulted in identifying a novel pathway linked to cardiovascular disease via generation of phenylacetylglutamine (PAGln). Through subsequent mechanistic studies, it was revealed that PAGln is a gut microbial metabolite that promotes heightened human platelet responsiveness to agonists in vitro and in vivo thrombosis potential using a mouse model of arterial injury (Nemet et al., Cell 180 (2020), 862-877).
In 2022, Dr. Nemet started her lab at the Clinic where she continued to study effects of gut-microbes produced molecules on the host.
Education & Professional Highlights
B.Sc. Biochemical Engineering, Faculty of Food Technology and Biotechnology, University of Zagreb, Croatia
M.Sc. Organic Chemistry, Faculty of Science, University of Zagreb, Croatia
Ph.D. Organic Chemistry, Faculty of Science, University of Zagreb, Croatia
"CIMER Trained Mentor" indicates the principal investigator has completed mentorship training based on curriculum from the Center for the Improvement of Mentored Experiences in Research, aimed at advancing mentoring relationships and promoting cultural change in research.
Research
Gut-microbes play an important role in maintaining host health. Multiple diseases including cardiovascular disease, type 2 diabetes, metabolic syndrome, and cancer are associated with altered gut microbial structure and function. Rational design of personalized therapeutic strategies that target gut microbiota driven pathways require a comprehensive understanding of gut microbial metabolism and the relationship between systemic levels of microbial metabolites and disease risks.
Our lab focuses on understanding the communication between gut microorganisms and their host. In particular, we study how microbial metabolic pathways contribute to overall changes in host physiology, and disease susceptibility. We work on identifying novel pathways of clinical relevance with mechanistic links to human diseases. Our approaches are based on use of targeted and untargeted metabolomics and clinical studies in tandem with mechanistic studies. Our models include conventionally raised and/or germ free host colonized with genetically engineered human commensals to demonstrate direct effects of particular enzyme/metabolite on the host.
Our Team
Selected Publications
Nemet I, Funabashi M, Li XS, Dwidar M, Sangwan N, Skye SM, Romano KA, Cajka T, Needham BD, Mazmanian SK, Hajjar AM, Rey FE, Fiehn O, Tang WHW, Fischbach MA, Hazen SL: Microbe-derived uremic solutes enhance thrombosis potential in the host. mBio. 2023 Nov 10;14(6):e0133123. doi: 10.1128/mbio.01331-23.
Nemet I*, Li XS, Haghikia A, Li L, Wilcox J, Romano KA, Buffa JA, Witkowski M, Demuth I, König M, Steinhagen-Thiessen E, Bäckhed F, Fischbach MA, Tang WHW, Landmesser U, Hazen SL. Atlas of gut microbe-derived products from aromatic amino acids and risk of cardiovascular morbidity and mortality. Eur Heart J. 2023 Jun 21;. doi: 10.1093/eurheartj/ehad333. *corresponding author
Witkowski M*, Nemet I*, Alamri H, Wilcox J, Gupta N, Nimer N, Haghikia A, Li XS, Wu Y, Saha PP, Demuth I, König M, Steinhagen-Thiessen E, Cajka T, Fiehn O, Landmesser U, Tang WHW, Hazen SL. The artificial sweetener erythritol and cardiovascular event risk. Nat Med. 2023 Mar;29(3):710-718. doi: 10.1038/s41591-023-02223-9; *equal contribution
Molinaro A*, Nemet I*, Bel Lassen P, Chakaroun R, Nielsen T, Aron-Wisnewsky J, Bergh P, Li L, Henricsson M, Køber L, Isnard R, Helft G, Stumvoll M, Pedersen O, Smith JG, Tang WHW, Clément K, Hazen SL, Bäckhed F, MetaCardis consortium. Microbially Produced Imidazole Propionate Is Associated With Heart Failure and Mortality. JACC Heart Fail. 2023 Apr 1;S2213-1779(23)00138-5. doi: 10.1016/j.jchf.2023.03.008. *equal contribution
Kitai T, Nemet I, Engelman T, Morales R, Chaikijurajai T, Morales K, Hazen SL, Tang WHW. Intestinal barrier dysfunction is associated with elevated right atrial pressure in patients with advanced decompensated heart failure. Am Heart J. 2022;245:78-80. doi: 10.1016/j.ahj.2021.11.014.
Lee Y*, Nemet I*, Wang Z, Lai HTM, de Oliveira Otto MC, Lemaitre RN, Fretts AM, Sotoodehnia N, Budoff M, DiDonato JA, McKnight B, Tang WHW, Psaty BM, Siscovick DS, Hazen SL, Mozaffarian D. Longitudinal Plasma Measures of Trimethylamine N-Oxide and Risk of Atherosclerotic Cardiovascular Disease Events in Community-Based Older Adults. J Am Heart Assoc. 2021; 10(17):e020646. doi: 10.1161/JAHA.120.020646. PMCID: PMC8649305; *equal contribution
Nemet I, Saha PP, Gupta N, Zhu W, Romano KA, Skye SM, Cajka T, Mohan ML, Li L, Wu Y, Funabashi M, Ramer-Tait AE, Naga Prasad SV, Fiehn O, Rey FE, Tang WHW, Fischbach MA, DiDonato JA, Hazen SL. A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors. Cell. 2020; 180(5):862-877.e22. doi: 10.1016/j.cell.2020.02.016. PMCID: PMC7402401
Choucair I*, Nemet I*#, Li L, Cole MA, Skye SM, Kirsop JD, Fischbach MA, Gogonea V, Brown JM, Tang WHW, Hazen SL. Quantification of bile acids: a mass spectrometry platform for studying gut microbe connection to metabolic diseases. J Lipid Res. 2020 Feb;61(2):159-177. doi: 10.1194/jlr.RA119000311. PMCID: PMC6997600; *equal contribution; #corresponding author
Careers
Research News
Inching closer to precision heart care medicine, Cleveland Clinic researchers develop an “atlas” of the human microbiome pathways linked to cardiac and mortality risks.