Ruthann Nichols, Ph.D.

Ruthann Nichols, Ph.D.

Associate Professor, Biological Chemistry
Adjunct Associate Professor, Chemistry

Office: 5220A MSRB III
Lab: 5200 MSRB III
1150 W. Medical Center Drive
Ann Arbor, MI 48109-5606


(734) 764-4467

Areas of Interest

We use an interdisciplinary research approach to understand the roles of peptides as messengers and regulators of critical physiological processes. We collaborate with our colleagues at The University of Michigan Medical School to translate our research from basic science to applied human health.

Our research is focused on RFamide peptides, a group of structurally-related brain-gut peptides conserved in all animals. Activities and tissue distribution data suggest RFamides are involved in regulating cardiovascular parameters; however, the underlying mechanisms and function of a RFamide are yet to be elucidated. Delineating molecular mechanisms involved in how a peptide impacts human cardiovascular physiology positions us to identify target molecules for drug development and therapy.

Cardiac failure can result from a structural or functional disorder that impairs the ability of the heart to fill or pump a sufficient amount of blood throughout the body in a timely manner. Diastole is the period of time when the heart relaxes after contraction, and the ventricles fill with blood. Diastolic dysfunction is a leading cause of morbidity and mortality; however, the mechanism(s) responsible for this devastating problem remain unresolved.

We began our research on RFamides, peptides structurally related by a common RFamide C terminus, in the model organism Drosophila melanogaster. We isolated the naturally-occurring RFamide peptide dromyosuppressin (DMS; TDVDHVFLRFamide). We generated DMS-specific antisera to avoid cross reactivity to other RFamide peptides, and found the peptide is present in the brain throughout all stages of development. In mapping the expression of the peptide we discovered DMS is synthesized in D. melanogaster brain and delivered to the heart. We developed whole animal bioassays to measure the activity of DMS in D. melanogaster; we determined DMS acts to slow cardiac contractions in vivo.

We recently translated our research from the fruitfly to humans. We discovered that a human peptide structurally similar to DMS slows cardiac relaxation, a component of diastole. This is a novel and exciting finding as it identifies an endogenous signaling agent that could contribute to diastolic dysfunction. The human DMS-like peptide may be a potential target molecule for drug development or diagnosis, or to develop future therapeutic strategies to address diastolic dysfunction in cardiovascular disease states.

The human DMS-like peptide exists; however, its expression, signal transduction pathway, and physiological function remain unknown. We will fill these critical scientific gaps. Our initial goals are to identify the human peptide receptor and delineate ligand-protein binding, and design and employ agonists and antagonist to investigate function. Our long term goals are to understand the role of the peptide in cardiac performance under physiological and pathological conditions, and its relevance and application to human health.

This research was supported by the American Heart Association, National Science Foundation, and National Institutes of Health.

Honors & Awards

Endowment for Basic Sciences Teaching Award, University of Michigan Medical School, 2011
University of Michigan Teaching Honor List, 1994

Published Articles or Reviews

In vitro model of ischemic heart failure using human induced pluripotent stem cell-derived cardiomyocytes.
Davis J, Chouman A, Creech J, Monteiro da Rocha A, Ponce-Balbuena D, Jimenez Vazquez EN, Nichols R, Lozhkin A, Madamanchi NR, Campbell KF, Herron TJ.
JCI Insight. 2021, in press.

The 5-amino acid N-terminal extension of non-sulfated drosulfakinin II is a unique target to generate novel agonists.
Leander M, Heimonen J, Brocke T, Rasmussen M, Bass C, Palmer G, Egle J, Mispelon M, Berry K, Nichols R.
Peptides. 2016; 83: 49–56.

Conserved molecular switch interactions in modeled cardioactive RF-NH2 peptide receptors: Ligand binding and activation.
Rasmussen M, Leander M, Ons S, Nichols R.
Peptides. 2015; 71: 259–67.

Cardiac contractility structure-activity relationship and ligand-receptor interactions; the discovery of unique and novel molecular switches in myosuppressin signaling.
Leander M, Bass C, Marchetti K, Maynard BF, Wulff JP, Ons S, Nichols R.
PLoS One. 2015; 10: e0120492.

Conserved residues in RF-NH₂ receptor models identify predicted contact sites in ligand-receptor binding.
Bass C, Katanski C, Maynard B, Zurro I, Mariane E, Matta M, Loi M, Melis V, Capponi V, Muroni P, Setzu M, Nichols R.
Peptides. 2014; 53: 278–85.

Structure-activity relationships of FMRF-NH2 peptides demonstrate A role for the conserved C terminus and unique N-terminal extension in modulating cardiac contractility.
Maynard BF, Bass C, Katanski C, Thakur K, Manoogian B, Leander M, Nichols R.
PLoS One. 2013; 8: e75502.

For a list of publications from PubMed, click HERE

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