Home

Ruthann Nichols, Ph.D.

Associate Professor, Biological Chemistry

B.S., M.S., Purdue University
Ph.D., Purdue University
Postdoctoral, Purdue University

Research Profile

Mechanisms and physiological functions of RFamide neuropeptides in Drosophila to humans; translating basic science to medicine.

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.

Awards

1994 University of Michigan Teaching Honor List

Publications

1: Palmer GC, Tran T, Duttlinger A, Nichols R. The drosulfakinin 0 (DSK 0) peptide encoded in the conserved Dsk gene affects adult Drosophila melanogaster crop contractions. Journal of Insect Physiology 2007 53:1125-33. PMID: 17632121

2: Nichols R. The first nonsulfated sulfakinin activity reported suggests nsDSK acts in gut biology. Peptides 2007 28:767-73. PMID: 17292511

3: Söhler S, Neupert S, Predel R, Nichols R, Stengl M. Localization of leucomyosuppressin in the brain and circadian clock of the cockroach Leucophaea maderae. Cell Tissue Research 2007 328:443-52. PMID: 17216199

4: Angioy AM, Muroni P, Barbarossa IT, McCormick J, Nichols R. Evidence dromyosuppressin acts at posterior and anterior pacemakers to decrease the fast and the slow cardiac activity in the blowfly Protophormia terraenovae. Peptides 2007 28:585-93. PMID: 17141921

nicholsr@umich.edu

Office: 5301C MSRB3, Box 5606
PH: (734)764-4467

PubMed: nichols r