Biology Department Faculty

We adopt an interdisciplinary approach in our research to address two complex and vital questions. Our primary objectives encompass: (a) characterizing the effects of viral insulin/IGF-1-like peptides (VILPs) on the insulin/IGF system and host-pathogen interactions, and (b) determining the role of the gut microbiome and microbiome-derived metabolites in Type 1 diabetes and celiac disease. As a result, we initially focus on two projects:

1. Characterization of Viral Insulin/IGF-1-like Peptides (VILPs): Our recent and exciting discovery has unveiled that viruses carry sequences strikingly similar to human peptide hormones. Specifically, we've identified six VILPs within the Iridoviridae virus family. In this comprehensive project, our aim is to comprehend how VILPs interact with the insulin/IGF-1 system, influencing receptors, downstream signaling, and related functions. We've already uncovered unique functions of VILPs including IGF-1 receptor inhibition. Furthermore, we're delving into the role of VILPs in host-pathogen interactions using the Grouper Iridovirus and zebrafish as model systems. 

2. The Role of Gut Microbiome in Autoimmunity: As autoimmune diseases become more prevalent and genetics alone can't explain their rise, attention has turned to environmental factors, including gut microbes and their products. We're actively investigating the role of gut microbes and their products in the autoimmunity of Type 1 Diabetes and Celiac Disease. To explore this, we're utilizing patient samples and mouse models of these diseases. Our focus includes understanding the molecular mimicry mechanism, examining specific bacterial species like Parabacteroides distasonis, and studying gut microbiota-derived metabolites. We're also embracing innovative approaches like IgA-sequencing and Pep-Seq to deepen our understanding of the interactions between the microbiome and the host.

1. Girdhar K, Dogru DY, Huang Q, Yang Y, Chrudinova M, Raisingani A, Oh J, Tolstikov V, Kiebish MA, Kelley K, Ludvigsson JF, Palm NW, Ludvigsson J, Altindis E. Dynamics of Gut Microbiome, IgA Response and Plasma Metabolome in Development of Pediatric Celiac Disease. Microbiome. 2023 Jan 13;11(1):9. doi: 10.1186/s40168-022-01429-2.

2. Moreau F, Kirk NS, Zhang F, Gelfanov V, List EO, Chrudinová M, Venugopal H, Lawrence MC, Jimenez V, Bosch F, Kopchick JJ, DiMarchi DR, Altindis E, Kahn CR. Interaction of a viral insulin-like peptide with the IGF-1 receptor produces a natural antagonist. Nature Communications. 2022 Nov 5;13(1):6700.

3. Girdhar K, Huang Q, Chow I, Raisingani A, Brady C, Atkinson M, Kwok W. Kahn CR, Altindis E. A Gut Microbial Peptide and Molecular Mimicry in the Pathogenesis of Type 1 Diabetes. PNAS. 2022 Aug 2;119(31):e2120028119

4. Girdhar K, Soto M, Huang Q, Orliaguet L, Cederquist C, Sundaresh B, Hu J, Figura M, Raisingani A, Canfora EE, Dirice E, Fujisaka S, Goossens GH, Blaak EE, Kulkarni RN, Kahn CR, Altindis E. Gut Microbiota Regulate Pancreatic Growth, Exocrine Function and Gut Hormones. Diabetes, 2022 Feb 25;db210382. doi: 10.2337/db21-0382.

5. Chrudinová M, Moreau F, Noh HL, Páníková T, Žáková L, Friedline R, Valenzuela F, Kim J, Jiráček J, Kahn CR, Altindis E. Characterization of Viral Insulins Reveals White Adipose Tissue Specific Effects in Mice. Mol Metab. 2020 Nov 18;101121. 

6. Altindis E, Cai W, Sakaguchi M, Zhang F, Guoxiao W, Liu F, Gelfanov V, De Meyts P, DiMarchi R and Kahn CR. Viral insulin-like peptides activate human insulin and IGF-1 receptor signaling: A paradigm shift for host-microbe interactions. PNAS, 2018 Mar 6;115 (10):2461-2466. 

7. Girdhar K, Powis M, Raisingani A, Chrudinová M, Huang R, Tran T, Sevgi K, Dogru YD, Altindis E*. Viruses and Metabolism: The Effects of Viral Infections and Viral Insulins on Host Metabolism. Annu Rev Virol. 2021 Sep 29;8(1):373-391.

8. Dedrick S, Sundaresh B, Huang Q, Brady C, Yoo T, Cronin C, Rudnicki C, Flood M, Momeni B, Ludvigsson J, Altindis E. The Role of Gut Microbiota and Environmental Factors in Type 1 Diabetes Pathogenesis. Front Endocrinol (Lausanne). 2020 Feb 26;11:78.

9. Huang Q, Kahn C.R, Altindis E. Viral Hormones: Expanding Dimensions in Endocrinology. Endocrinology, 2019, Volume 160, Issue 9, September, 2165–2179.