Chambers, Jeremy Wayne
Title: Assistant Professor
Office: AHC4 232
Department(s): Cellular Biology and Pharmacology
The focus of the Chambers Lab is to understand how communication among mitochondria and between mitochondria and other organelles influences aging and age-related diseases. Our emphasis is to investigate how signaling complexes on the mitochondrial surface affect aging, physiology, mitochondrial functions, and cellular viability. The Chambers Lab examines these questions using multidisciplinary approaches that employ biochemical, cellular, and rodent-based experiments to explore promising mitochondrial communication conduits.
Mitochondria are highly dynamic organelles that produce energy for cells. During physiological changes such as exercise, diet, development, stress, and injury, mitochondria play a crucial role in the production of reactive oxidants, maintenance of ion concentrations, and induction of apoptosis. For these reasons, mitochondrial dysfunction is a hallmark of aging and degenerative diseases, such as Parkinson’s disease, primary myopathies, and diabetes.
Scaffold proteins organize signaling components into distinct lines of communication in order to regulate cellular functions. Scaffold proteins on the outer mitochondrial membrane facilitate mitochondrial-cell communication as well as communication among mitochondria in a similar manner to how synapses conduct neurotransmissions. Unfortunately, these mitochondrial switchboards remain largely uninvestigated. Sab is an outer mitochondrial scaffold linked to mitochondrial dysfunction and cell death. Recent studies in our lab have demonstrated that Sab levels increase with age. Our lab is interested in understanding how this change influences mitochondrial function and aging.
The main goals of our research are: 1.) to identify scaffold proteins on the outer mitochondrial membrane that contribute to mitochondrial function and aging, 2) to determine the signaling cascades associated with individual scaffold proteins, 3) to elucidate the molecular mechanisms by which these protein complexes influence mitochondrial physiology, aging, and age-related disease.
To address these questions, our lab has developed many assays to probe cellular biology in a high throughput capacity. As a secondary area of research, our lab continues to engage in novel assay development to monitor physiology and for drug discovery related to age-related diseases, cancer, cardiovascular disease, and primary myopathies.
- Prado, A, Petroianu, GA, Lorke, DE, and Chambers, JW. A Trivalent Approach for Determining In Vitro Toxicology: Examination of Oxime K027. Journal of Applied Toxicology. (Published Online May 22, 2014).
- Chambers JW, et al. Inhibition of JNK mitochondrial localization and signaling is protective against ischemia/reperfusion injury in rats. Journal of Biological Chemistry. 288(6). (2013). 4000-11.
- Chambers JW, et al. Blocking c-jun N-terminal Kinase (JNK) Translocation to the Mitochondria Prevents 6-hydroxydopamine-induced Toxicity in vitro and in vivo. Journal of Biological Chemistry. 288(2). (2013). 1079-87.
- Chambers, JW, et al. Selective Inhibition of Mitochondrial JNK Signaling Achieved Using Peptide Mimicry of the Sab Kinase Interacting Motif-1 (KIM1). ACS Chemical Biology. 6(8). (2011). 808-818.
- Chambers, JW and LoGrasso, PV. Mitochondrial c-jun N-Terminal Kinase (JNK) Signaling Initiates Physiological Changes Resulting in Amplification of Reactive Oxygen Species Generation. Journal of Biological Chemistry. 286(18). (2011). 6052-16062.
- Chambers, JW, et al. Small Molecule c-jun N-terminal Kinase (JNK) Inhibitors Protect Dopaminergic Neurons in a Model of Parkinson’s Disease. ACS Chemical Neuroscience. 2(4). (2011). 198-206.