Gautam Goel, PhD
Gautam Goel received his PhD in Bioengineering from the Georgia Institute of Technology, where he specialized in Dynamical Systems Analysis of biological pathways using ordinary differential equation-based kinetic models. Subsequently, he was a Research Fellow at Massachusetts General Hospital and The Broad Institute, where he investigated mechanisms of Inflammatory Bowel Disease (IBD) pathogenesis and discovered druggable targets and drug candidates.
Next, he moved to industry and spearheaded cross-functional R&D operations as Director of Precision Medicine at a biotech startup to accelerate path to clinical development for an antigen-specific immunotherapy for type 1 diabetes. Simultaneously, he led the biomarker discovery program in celiac disease, which resulted in the first blood-based diagnostic for patients on a gluten-free diet. He also developed an immune response monitoring toolkit to support Phase 2 clinical trials for an antigen-specific peptide vaccine to treat celiac disease.
Dr. Goel's work has led to over 40 publications in disease areas including Crohn’s disease, ulcerative colitis, celiac disease, chronic inflammation and infectious diseases. He advises biotech and pharmaceutical companies on challenges in early-stage target discovery, lead candidate drug identification and biomarker analysis for clinical development. Dr. Gautam has enabled his clients to raise tens of millions of dollars in dilutive as well as non-dilutive funding on the basis of machine-learning based target and drug discovery pipelines that he has helped design and build
Area of Research
Dr. Goel’s research and interest lie in dynamical analysis of biological systems. The research group's goal is to study and characterize the dynamical behavior of the immune system in health and disease and develop an operational understanding of how nonlinearities in interactions among the system components govern response to external perturbations such as vaccines and drugs. While their primary focus is the immune system, they explore longitudinal behavior with multiscale datasets including, but not limited to, cytometry, single cell- and bulk- RNA-seq, proteomics and perturbation-omics data. The phenomena that they study include all kinds of time-varying behavior such as breadth of immunotype heterogeneity across populations, resilience of immunotype variability over time, and acute responses to vaccines and drugs.
A key biological phenomena of interest in the research group is Advanced (Immune) Aging in the context of autoimmune diseases. Chronic and systemic inflammation is characteristically low-grade and persistent, ultimately leading to collateral damage to tissues and organs. Quantitative metrics and models that can capture the non-linear axis of immune clock of aging have been critically lacking. The group recently identified a cellular composite metric for quantifying the degree of advanced aging in Down syndrome. Future research focuses on studying the inter- and intra- individual variability around the Advanced Aging axis and its potential for patient stratification, diagnostic selection, therapeutic selection and predicting disease progression and treatment response.
Goel, G, King T, Daveson J, et. al. (2016) Epitope-specific immunotherapy targeting CD4-positive T cells in coeliac disease: two randomised, double-blind, placebo-controlled phase I studies. Lancet Gastroenterol Hepatol. Volume 2, No. 7, p479–493, July 2017. doi: 10.1016/S2468-1253(17)30110-3
Goel, G, Tye-Din JA, et. al. (2019) Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease. Science Advances. 2019 Aug 7;5(8):eaaw7756. doi: 10.1126/sciadv.aaw7756
Hardy MY, Goel, G, et. al. (2021) A sensitive whole blood assay detects antigen-stimulated cytokine release from CD4+ T cells and facilitates immunomonitoring in a phase 2 clinical trial of Nexvax2 in celiac disease. Front. Immunol. 12:661622. doi: 10.3389/fimmu.2021.661622
Conway, K. L., Goel, G., Sokol, H., Manocha, M., Mizoguchi, E., Terhorst, C., et al. (2012). p40phox expression regulates neutrophil recruitment and function during the resolution phase of intestinal inflammation. J Immunol. 2012 Oct 1;189(7):3631-40. doi: 10.4049/jimmunol.1103746
Reese, T. A., Wakeman, B. S., Choi, H. S., Hufford, M. M., Huang, S. C., Zhang, X., et al. (2014). Helminth infection reactivates latent γ-herpesvirus via cytokine competition at a viral promoter. Science. 2014 Aug 1;345(6196):573-7. doi: 10.1126/science.1254517
Tannahill, G. M., Curtis, A. M., Adamik, J., Palsson-McDermott, E. M., McGettrick, A. F., Goel, G., et al. (2013). Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature. 2013 Apr 11;496(7444):238-42. doi: 10.1038/nature11986
Palsson-McDermott, E. M., Curtis, A. M., Goel, G., et al. (2015). Pyruvate Kinase M2 Regulates Hif-1α Activity and IL-1β Induction and Is a Critical Determinant of the Warburg Effect in LPS-Activated Macrophages. Cell Metab.2015Jan 6;21(1):65-80. doi: 10.1016/j.cmet.2014.12.005
Goel, G., Conway, K. L., Jaeger, M., Netea, M. G., & Xavier, R. J. (2014). Multivariate inference of pathway activity in host immunity and response to therapeutics. Nucleic Acids Res. 2014;42(16):10288-306. doi: 10.1093/nar/gku722
Hwang, S., Maloney, N. S., Bruinsma, M. W., Goel, G., Duan, E., Zhang, L., et al. (2012). Nondegradative role of Atg5-Atg12/ Atg16L1 autophagy protein complex in antiviral activity of interferon gamma. Cell Host Microbe. 2012 Apr 19;11(4):397-409. doi: 10.1016/j.chom.2012.03.002
Graham DB, Jasso GJ, Mok A, Goel G, et al. Nitric oxide engages an anti-inflammatory feedback loop mediated by peroxiredoxin 5 in phagocytes. Cell Reports. Online July 24, 2018. DOI: 10.1016/j.celrep.2018.06.081
Graham, D. B., Becker C. E., Doan A., Goel, G., et al. (2015) Functional Genomics Identifies Negative Regulatory Nodes Controlling Phagocyte Oxidative Burst. Nature Communications. Jul 21;6:7838. doi: 10.1038/ncomms8838.
Khor B., Gagnon J., Goel, G., et al. (2015) The kinase DYRK1A reciprocally regulates the differentiation of Th17 and regulatory T cells. Elife. 2015 May 22;4. doi: 10.7554/eLife.05920.