Lee D. Chaves, Ph.D.

Professional Background

Dr. Chaves graduated from the University of Minnesota with a BA in Physiology and a PhD in Comparative Molecular Biosciences. His interdisciplinary doctoral program was focused on molecular biology, genetics, and immunology studying the major histocompatibility complex of domestic turkeys. He completed a postdoctoral fellowship in immunology at National Jewish Health in Denver and a second fellowship in immunology and nephrology at the University of Chicago. His current research interests are focused on the molecular genetics/epigenetics of age-related diseases and disabilities using in vitro viral transduction, cellular immortalizations, and CRISPR/dCas9 techniques genome editing techniques.

Aging affects many forms of epigenetic regulation (histone acetylation, methylation, phosphorylation, etc.) as well as the profiles of circulating miRNA. An exciting development is the recent recognition that miRNA profiles and specific miRNAs are associated with frailty and cognitive status. This is of particular interest as miRNA profiling has the potential to be a strong diagnostic and/or prognostic indicator.

Short (18-22 ribonucleotides), non-coding micro-RNAs (miRNAs) were originally identified in Caenorhabditis elegans, a small worm often used as the model for developmental biology. They were found to be potent post-transcriptional regulators of mRNA translation by binding the 3` untranslated regions of targets, which leads to a coordinated molecular degradation. For many years it was thought miRNAs were exclusive to C. elegans, and since have been identified in nearly all animal species, often highly conserved. The molecular machinery responsible for miRNA activity is the basis for now common siRNA/shRNA knockdown techniques.
Broadly expressed and often secreted, miRNAs have been isolated in blood, solid organs and tissues, and even in urine. Altogether, miRNAs are now thought to be significant contributors to organismal homeostasis and disease states.

• BA, Physiology, University of Minnesota, Minneapolis , MN
• PhD, Comparative Molecular Biosciences, University of Minnesota, Minneapolis, MN
• Post Doctoral Fellowship, Immunology & Nephrology, University of Chicago, Chic, IL
• Post Doctoral Fellowship, Immunology, National Jewish Health, Denver, CO

Research

Overview

We employ in vitro molecular genetics and cell models as well as in vivo mouse models to study many of the mechanisms of aging. In our cell models we use genetic knock-in, knock-out, and CRISPR techniques, through transient transfection and/or stable viral transduction, to manipulate gene expression and study their role in cellular aging pathways. Similarly, we use genetically modified (knock-in/knock-out) and aged (24-30 month) mouse models studying in vivo aging mechanisms and epigenetic modifications.

Additionally, we have begun clinical studies into epigenetics in aging individuals in order to better understand some common age-associated disorders such as frailty, cognition, and physical performance.

• Bryniarski, M., A, Sandoval, R., M, Ruszaj, D., M, Fraser-McArthur, J, Yee, B., M, Yacoub, R, Chaves, L., D, Campos-Bilderback, S., B, Molitoris, B., A, Morris, M., E. 2023. Defining the Intravital Renal Disposition of Fluorescence-Quenched Exenatide.. Molecular pharmaceutics, 20 (2), 987-996
• Heo, Jeongyun, Sobiech, Thomas., A., Kutscher, Hilliard., L., Chaves, Lee, Sukumaran, Dinesh., K., Karki, Shanta, Dube, Admire, Prasad, Paras., N., Reynolds, Jessica., L.. 2021. Hybrid Curdlan Poly(γ ‐Glutamic Acid) Nanoassembly for Immune Modulation in Macrophage. Macromolecular Bioscience, 21 (1). https://doi.org/10.1002/mabi.202000358
• Chaves, L., D, Abyad, S, Honan, A., M, Bryniarski, M., A, McSkimming, D., I, Stahura, C., M, Wells, S., C, Ruszaj, D., M, Morris, M., E, Quigg, R., J, Yacoub, R. 2021. Unconjugated p-cresol activates macrophage macropinocytosis leading to increased LDL uptake.. JCI insight, 6 (11)
• Bryniarski, M., A, Zhao, B, Chaves, L., D, Mikkelsen, J., H, Yee, B., M, Yacoub, R, Shen, S, Madsen, M, Morris, M., E. 2021. Immunoglobulin G Is a Novel Substrate for the Endocytic Protein Megalin.. The AAPS journal, 23 (2), 40