Tight regulation of neurotransmitter release at synaptic connections between nerve cells is essential for maintaining stability and fidelity in the function of neural circuits. Accumulating evidence suggests that intrinsic mechanisms in neurons are at play to ensure that the amount of neurotransmitter release is adjusted efficiently and appropriately to achieve balance or homeostasis. Current experimental findings suggest that loss of homeostatic mechanisms in the nervous system may be among the earliest defects associated with age-dependent neurodegenerative disease.
The Haghighi lab investigates the molecular mechanisms that underlie synaptic homeostasis and regulate neurotransmitter release. We have discovered an important link between nutrient intake and the regulation of synaptic homeostasis, highlighting key molecular players in this process. In addition, our recent work has identified a role for a Parkinson’s-related gene in the regulation of synaptic homeostasis. Using both fly and mouse models, we are testing the hypothesis that an optimally functioning nervous system can enhance systemic healthspan and ultimately extend organismal lifespan.
Why it matters
We believe that our research program provides an alternative perspective on neurodegenerative disease, a perspective aimed at designing novel therapeutic approaches for preventing neurodegeneration rather than tackling its symptoms. In addition, through better understanding of the molecular mechanisms underlying synaptic homeostasis, we hope to pave the way for designing drugs that extend our healthspan by making neurons healthier and optimally functional.
What if neuronal dysfunction is a driver of aging, rather than a symptom of it? We are developing strategies to optimize neuronal function, thereby improving the function of all organs and extending the healthy years of life.
Pejmun Haghighi, PhD
Dr. Haghighi, a native of Iran, received his PhD from McGill University in Montreal, Canada, which was followed by a postdoctoral fellowship at the University of California, Berkeley. Dr. Haghighi was later recruited back to McGill University, where he taught and conducted research and became a tenured associate professor. He moved his laboratory to the Buck Institute in 2013.
Ammar Aly PhD Candidate, USC-Buck Biology of Aging Program
Ammar is a 3rd year Ph.D. student in the Biology of Aging program at USC. He obtained his B.A. in developmental biology from Harvard College in 2017. He then spent three years as a research assistant in Dr. Paul Greengard’s laboratory at the Rockefeller University. There, he investigated the molecular signaling cascades that mediate the delayed action of antidepressant drugs. Now in the Haghighi Lab, Ammar is studying how the autonomic nervous system can be leveraged to direct stem cell fate.
Jill Farnsworth, PhD Postdoctoral Research Fellow
Jill received her Bachelor of Science with honors in neuroscience at Indiana University. She continued her neuroscience focus in graduate school and received her PhD from the University of Montana. Jill has had the pleasure of researching cannabinoid receptor signaling properties during her undergraduate career and pharmacological modulation of N-methyl-D-aspartate (NMDA) receptor activity as a graduate student. She is now exploring properties of synaptic homeostasis in the Haghighi lab during her postdoctoral training.
Olfat Malak, PhD Postdoctoral Research Scholar
Olfat is an electrophysiologist by training who obtained her bachelor’s degree in human and animal developmental biology at the Lebanese University, Beirut, Lebanon. She received her Master’s and PhD at the University of Nantes, Institut du thorax, Nantes, France. During her PhD, Olfat studied the molecular mechanisms underlying cardiac, neuronal and muscular channelopathies using peptides that mimic specific parts of ion channels. She then received a visiting junior scholar fellowship from the France-Stanford Center for Interdisciplinary Studies and joined Dr. Joseph Wu’s lab at Stanford University to model cardiac diseases using patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Now with the Haghighi Lab, she aims to improve our understanding of how synaptic transmission in sympathetic nervous system regulates organ function as people age.
Jeri Martensen Lab Technician
Jeri joined the Haghighi Lab as an intern in December of 2019. After a year of apprenticeship, she was hired as a lab technician and continues to assist in multiple projects pertaining to how diet and genetics may affect synaptic homeostasis using drosophila. Jeri is a bright young woman currently working on her undergraduate degree in biochemistry at the Santa Rosa Junior College. Due to her passion and commitment to learning, she has been able to work closely with the biological sciences department at her school as a TA in anatomy and biology courses.
Jeri has also had the opportunity to shadow and volunteer with doctors in her local community. Currently a volunteer at the Santa Rosa Humane Society, Jeri has a strong passion for animals and health.
During her spare time, she enjoys being in nature, singing, knitting, and sharing good food with friends and loved ones.
Myriam Moujahidine Administrative Lab Manager
Myriam obtained her master’s degree in Molecular Biology at l'Université de Montréal, Montreal, Canada. She worked for 4 years as research assistant at McGill University, Montreal, Canada. Before re-joining the Haghighi Lab at the Buck, she also worked 6 years as a public health specialist for the Communication Branch of the Canadian Institute for Health Information (CIHI).
Andrew Rosko Research Associate
M. C.Mario Calderon
H. C.Helen Cifuentes
C. D.Cameron DuBose
L. G.Lindsay Gray
G. K.Grant Kauwe, PhD
E. L.Edward Liao, PhD
E. M.Elie Maksoud
J. F.Jessica Feria Pliego
- Maksoud E., Liao E. H., and Haghighi A.P.* (2019) A Neuron-Glial Trans-Signaling Cascade Mediates LRRK2-Induced Neurodegeneration. Cell Reports., DOI: j.celrep.2019.01.077
- Liao, E. H., Gray, L., Tsurudome, K., El-Mounzer, W., Elazzouzi, F., Baim, C., Farzin, S., Calderon, M. R., Kauwe, G., Haghighi, A.P. (2018). Kinesin Khc-73/KIF13B modulates retrograde BMP signaling by influencing endosomal dynamics at the Drosophila neuromuscular junction. PLoS Genetics, 14(1), e1007184.
- Chong, Y., Saviuk, N., Pie, B., Basisty, N., Quinn, R., Schilling, B., Sonenberg, N., Cooper, E., Haghighi A. P. (2018). Refinement of synapses without postsynaptic activity: Role for a 4E-BP regulated mechanism. Cell Reports, 23, 11–22. DOI: 10.1016/j.celrep.2018.03.040.
- Kauwe, G., Tsurudome, K., Penney, J., Mori, M., Gray, L., Calderon, M. R., Sonenberg, N., Haghighi, A. P. (2016). Acute fasting regulates retrograde synaptic enhancement through a 4E-BP-dependent mechanism. Neuron, 92, 1204–1212.
- Penney, J., Tsurudome, K., Liao, E. H., Kauwe, G., Gray, L., Yanagiya, A., Calderon, M. R., Sonenberg, N., Haghighi, A. P. (201 July 19). LRRK2 regulates retrograde synaptic compensation at the Drosophila neuromuscular junction. Nature Comm, 7, 12188. DOI: 10.1038/ncomms12188.
- Penney, J., Tsurudome, K., Liao, E. H., Livingstone, M., Gonzalez, M., Sonenberg, N., Haghighi, A. P. (2012 Apr 12). TOR is required for the retrograde regulation of synaptic homeostasis at the Drosophila neuromuscular junction. Neuron, 74(1), 166–178.
- Tsurudome, K., Tsang, K., Liao, E. H., Yang, J. S., Elazzouzi, F., He, T., Chishti, A., Lnenicka, G., Lai, E. C., Haghighi, A. P. (2012). The Drosophila miR-310 cluster negatively regulates synaptic strength at the neuromuscular junction. Neuron, 68, 879–893.
- Ball, R. W., Warren-Paquin, M., Tsurudome, K., Liao, E., Elazzouzi, F., Cavanagh, C., An, B. S., Wang, T. T., White, J. H., Haghighi, A. P. (2012 May 27). Retrograde BMP signaling controls synaptic growth at the NMJ by regulating Trio expression in motor neurons. Neuron, 66(4), 536–49.