Joined the Department in 2009
- B.S., 1994, Texas A&M University, Biochemistry, Genetics.
- Ph.D., 2001, Stanford University.
- Postdoctoral research, Stanford University.
Dr. Harlow has a long-standing interest in understanding the molecular mechanisms that underlie neurotransmission at the synapse. Currently there are two main research topics in the laboratory.
The first area of research in the Harlow laboratory deals with how synapses regulate protein synthesis. The regulation of protein synthesis at the chemical synapse is critical for learning and memory in healthy individuals, and is disrupted in a number of diseases such as Alzheimer’s diseases, schizophrenia, and autism. It has long been appreciated that protein synthesis is necessary for both the consolidation of new memories and the reconsolidation of existent memories. In neurons, much of the protein synthesis occurs away from the cell body at specialized regions within the dendritic arbor and postsynaptic spines, and is referred to as local protein synthesis. Local protein synthesis at the synapse is regulated by the presynaptic activity of synaptic vesicles (SVs), and requires a host of translation factors, ribosomes, mRNAs, and small non-coding RNAs (sRNAs; 20-50 nucleotides [nt] in length). The laboratory has recently discovered a novel class of sRNAs conserved across vertebrate synapses. Although these sRNAs have been implicated in different aspects of post-transcriptional control of protein translation in other tissues, their precise role at the neuronal synapse is still a mystery. In order to understand the normal regulation of local protein synthesis in the CNS, the Harlow lab is investigating the function of these sRNAs at the synapse. In the long-term, the laboratory believes these studies will contribute meaningfully to a framework whereby the detailed mechanisms of normal synaptic physiology can inform future investigation into the causes of numerous neurological disorders.
The second area of research in the Harlow laboratory deals with how energy is regulated at the synapse. The disruption of energy at the synapse, or more broadly any cell or organ, can lead to metabolic syndrome. Metabolic syndrome is a broad clinical term. It describes a cluster of risk factors that include diabetes and obesity, cardio-metabolic imbalance, and inflammation. Metabolic syndrome is linked to Alzheimer’s, Parkinson’s, and heart disease. At the cellular level, metabolism is controlled by the mitochondria, and each cell’s mitochondria are custom built to use a unique balance of energetic molecules that will ultimately be coupled with oxygen to produce energy, metabolites, and carbon dioxide. Energetic cells, such as cardiac muscle cells, dopaminergic and cholinergic neurons, possess mitochondria that are designed to tightly couple oxygen with energetic molecules such as triglycerides in order to produce energy. Any disruption of this coupling can lead to the production of radical oxygen species that are damaging to the mitochondria, and can ultimately trigger premature cell death. The Harlow laboratory has recently discovered a novel pathway, conserved across species, in the nervous and heart cells most susceptible to metabolic syndrome disease, that offers new insight into the unique metabolic circuit of these cells. The laboratory is studying this unique metabolic circuit in order to understand how energy is regulated at the synapse. The long-term goal of the Harlow laboratory is to expand on these findings in order to provide potential preventive or therapeutic agents for the treatment of metabolic syndrome.
- Lee, YI, Thompson, WJ, Harlow, ML. Schwann cells participate in synapse elimination at the developing neuromuscular junction. Curr. Opin. Neurobiol. 2017;47 :176-181. doi: 10.1016/j.conb.2017.10.010. PubMed PMID:29121585 .
- Stavrianakou, M, Perez, R, Wu, C, Sachs, MS, Aramayo, R, Harlow, M et al.. Draft de novo transcriptome assembly and proteome characterization of the electric lobe of Tetronarce californica: a molecular tool for the study of cholinergic neurotransmission in the electric organ. BMC Genomics. 2017;18 (1):611. doi: 10.1186/s12864-017-3890-4. PubMed PMID:28806931 PubMed Central PMC5557070.
- Li, H, Wu, C, Aramayo, R, Sachs, MS, Harlow, ML. Synaptic vesicles isolated from the electric organ of Torpedo californica and from the central nervous system of Mus musculus contain small ribonucleic acids (sRNAs). Genom Data. 2017;12 :52-53. doi: 10.1016/j.gdata.2017.02.015. PubMed PMID:28367405 PubMed Central PMC5361766.
- Li, H, Wu, C, Aramayo, R, Sachs, MS, Harlow, ML. Synaptic vesicles contain small ribonucleic acids (sRNAs) including transfer RNA fragments (trfRNA) and microRNAs (miRNA). Sci Rep. 2015;5 :14918. doi: 10.1038/srep14918. PubMed PMID:26446566 PubMed Central PMC4597359.
- Li, H, Harlow, ML. Individual synaptic vesicles from the electroplaque of Torpedo californica, a classic cholinergic synapse, also contain transporters for glutamate and ATP. Physiol Rep. 2014;2 (1):e00206. doi: 10.1002/phy2.206. PubMed PMID:24744885 PubMed Central PMC3967689.
- Harlow, ML, Szule, JA, Xu, J, Jung, JH, Marshall, RM, McMahan, UJ et al.. Alignment of synaptic vesicle macromolecules with the macromolecules in active zone material that direct vesicle docking. PLoS ONE. 2013;8 (7):e69410. doi: 10.1371/journal.pone.0069410. PubMed PMID:23894473 PubMed Central PMC3718691.
- Szule, JA, Harlow, ML, Jung, JH, De-Miguel, FF, Marshall, RM, McMahan, UJ et al.. Regulation of synaptic vesicle docking by different classes of macromolecules in active zone material. PLoS ONE. 2012;7 (3):e33333. doi: 10.1371/journal.pone.0033333. PubMed PMID:22438915 PubMed Central PMC3306385.
- Manson, MD, Harlow, ML. A grand view of the flagellar motor. J. Bacteriol. 2009;191 (16):5023-5. doi: 10.1128/JB.00695-09. PubMed PMID:19542284 PubMed Central PMC2725599.
- Nagwaney, S, Harlow, ML, Jung, JH, Szule, JA, Ress, D, Xu, J et al.. Macromolecular connections of active zone material to docked synaptic vesicles and presynaptic membrane at neuromuscular junctions of mouse. J. Comp. Neurol. 2009;513 (5):457-68. doi: 10.1002/cne.21975. PubMed PMID:19226520 PubMed Central PMC4288958.
- Ress, DB, Harlow, ML, Marshall, RM, McMahan, UJ. Methods for generating high-resolution structural models from electron microscope tomography data. Structure. 2004;12 (10):1763-74. doi: 10.1016/j.str.2004.07.022. PubMed PMID:15458626 PubMed Central PMC4312110.