42728-Dhayalan, Balamurugan

Balamurugan Dhayalan, PhD

Assistant Research Professor of Biochemistry, Molecular Biology & Pharmacology

Address
MS 4041
BIOM
IN
Indianapolis, IN
PubMed:

Bio

Dr. Dhayalan is an Assistant Research Professor of Biochemistry and his research focuses on insulin chemistry, protein folding, and the molecular mechanisms of diabetes. His laboratory addresses two fundamental questions: How can we make insulin more stable and effective as a therapeutic, and how does proinsulin misfolding contribute to β-cell dysfunction in diabetes?

One major focus is the development of improved insulin analogs through non-standard amino acid mutagenesis. By applying principles of physical chemistry, protein structure, and chemical biology, his research has developed diselenide- and halogenated insulin analogs with enhanced stability and resistance to fibrillation while maintaining biological activity. These approaches have the potential to improve the stability, shelf life, and accessibility of insulin therapeutics.

A second focus is understanding how disease-associated proinsulin mutations cause misfolding, ER stress, and diabetes. His studies of Mutant INS-gene Induced Diabetes of Youth (MIDY) combine protein synthesis, NMR spectroscopy, biophysical analysis, and cell biology to connect molecular defects in proinsulin folding with ER stress and clinical age of disease onset.

Key Publications

Yang Y, Dhayalan B, Ehnbom A, Weil-Ktorza O, Metanis N, Weiss MA. Damping amyloid-associated conformational fluctuations in a protein by an engineered diselenide bridge. Protein Sci. 2026 Aug;35(8):e70697. doi: 10.1002/pro.70697. PubMed PMID: 42478539; PubMed Central PMCID: PMC13386395.

El Hage K, Dhayalan B, Chen YS, Phillips NB, Whittaker J, Carr K, Whittaker L, Phillips MH, Ismail-Beigi F, Meuwly M, Weiss MA. Stabilization of a protein by a single halogen-based aromatic amplifier. Protein Sci. 2025 Mar;34(3):e70064. doi: 10.1002/pro.70064. PubMed PMID: 39969055; PubMed Central PMCID: PMC11837044.

Dhayalan B, Chen YS, Ni CL, Weiss MA. Synthetic studies of the mutant proinsulin syndrome demonstrate correlation between folding efficiency and age of diabetes onset. Int J Pept Res Ther. 2025 Jan;31(1). doi: 10.1007/s10989-024-10665-z. Epub 2024 Nov 20. PubMed PMID: 39866851; PubMed Central PMCID: PMC11759498.

Dhayalan B, Glidden MD, Zaykov AN, Chen YS, Yang Y, Phillips NB, Ismail-Beigi F, Jarosinski MA, DiMarchi RD, Weiss MA. Peptide Model of the Mutant Proinsulin Syndrome. I. Design and Clinical Correlation. Front Endocrinol (Lausanne). 2022;13:821069. doi: 10.3389/fendo.2022.821069. eCollection 2022. PubMed PMID: 35299972; PubMed Central PMCID: PMC8922534.

Chen YS, Gleaton J, Yang Y, Dhayalan B, Phillips NB, Liu Y, Broadwater L, Jarosinski MA, Chatterjee D, Lawrence MC, Hattier T, Michael MD, Weiss MA. Insertion of a synthetic switch into insulin provides metabolite-dependent regulation of hormone-receptor activation. Proc Natl Acad Sci U S A. 2021 Jul 27;118(30). doi: 10.1073/pnas.2103518118. PubMed PMID: 34290145; PubMed Central PMCID: PMC8325334.

Rege NK, Liu M, Yang Y, Dhayalan B, Wickramasinghe NP, Chen YS, Rahimi L, Guo H, Haataja L, Sun J, Ismail-Beigi F, Phillips NB, Arvan P, Weiss MA. Evolution of insulin at the edge of foldability and its medical implications. Proc Natl Acad Sci U S A. 2020 Nov 24;117(47):29618-29628. doi: 10.1073/pnas.2010908117. Epub 2020 Nov 5. PubMed PMID: 33154160; PubMed Central PMCID: PMC7703552.

Research Labs

Faculty research at IU School of Medicine is transforming health. Details about the medical research being conducted in faculty labs throughout IU School of Medicine are available in the Research section of this site.
Faculty Labs