Faculty Appointments
Professor of Molecular Physiology and Biophysics
Louise B. McGavock Chair
Education
Ph.D., Anatomy, University of California, Los Angeles, CaliforniaA.B., Zoology, University of California, Berkeley, California
Research Description
Developmental Neurobiology of Limbic, Hypothalamic and Autonomic Neural Architecture. During perinatal periods of development, environmental signals impact hypothalamic development in ways that alter homoeostasis throughout the life of the individual. The Simerly laboratory studies how the adipocyte hormone leptin functions to specify the structure and function of neural circuits known to control multiple aspects of metabolism and behavior. This work relies on utilization of molecular genetics and advanced cellular imaging techniques to visualize and manipulate central neural pathways. Recent findings indicate that leptin is a major developmental factor influencing metabolic programming of the hypothalamus by a variety of environmental factors, including nutrition. By using genetically targeted fluorescent labels, and both in vitro and in vivo conditional regulation of gene expression, ongoing studies are focused on determining if manipulations of genes known to participate in brain development also influence the development of leptin-sensitive pathways that mediate hypothalamic responses to changes in energy balance, with direct implications for the developmental origins of obesity and diabetes.
Research Keywords
Developmental neurobiology, neuroanatomy, neural circuits, limbic region and hypothalamus, neuroendocrinology, mouse molecular genetics, cellular imaging and image analysis
Publications
Williford KM, Taylor A, Melchior JR, Yoon HJ, Sale E, Negasi MD, Adank DN, Brown JA, Bedenbaugh MN, Luchsinger JR, Centanni SW, Patel S, Calipari ES, Simerly RB, Winder DG. BNST PKCd neurons are activated by specific aversive conditions to promote anxiety-like behavior. Neuropsychopharmacology [print-electronic]. 2023 Jun; 48(7): 1031-41. PMID: 36941364, PMCID: PMC10209190, PII: 10.1038/s41386-023-01569-5, DOI: 10.1038/s41386-023-01569-5, ISSN: 1740-634X.
Bedenbaugh MN, Brener SC, Maldonado J, Lippert RN, Sweeney P, Cone RD, Simerly RB. Organization of neural systems expressing melanocortin-3 receptors in the mouse brain: Evidence for sexual dimorphism. J Comp Neurol [print-electronic]. 2022 Nov; 530(16): 2835-51. PMID: 35770983, PMCID: PMC9724692, DOI: 10.1002/cne.25379, ISSN: 1096-9861.
Luchsinger JR, Fetterly TL, Williford KM, Salimando GJ, Doyle MA, Maldonado J, Simerly RB, Winder DG, Centanni SW. Delineation of an insula-BNST circuit engaged by struggling behavior that regulates avoidance in mice. Nat Commun. 2021 Jun 6/11/2021; 12(1): 3561. PMID: 34117229, PMCID: PMC8196075, PII: 10.1038/s41467-021-23674-z, DOI: 10.1038/s41467-021-23674-z, ISSN: 2041-1723.
Sweeney P, Bedenbaugh MN, Maldonado J, Pan P, Fowler K, Williams SY, Gimenez LE, Ghamari-Langroudi M, Downing G, Gui Y, Hadley CK, Joy ST, Mapp AK, Simerly RB, Cone RD. The melanocortin-3 receptor is a pharmacological target for the regulation of anorexia. Sci Transl Med. 2021 Apr 4/21/2021; 13(590): PMID: 33883274, PMCID: PMC9022017, PII: 13/590/eabd6434, DOI: 10.1126/scitranslmed.abd6434, ISSN: 1946-6242.
Biddinger JE, Lazarenko RM, Scott MM, Simerly R. Leptin suppresses development of GLP-1 inputs to the paraventricular nucleus of the hypothalamus. Elife. 2020 Nov 11/18/2020; 9: PMID: 33206596, PMCID: PMC7673779, PII: 59857, DOI: 10.7554/eLife.59857, ISSN: 2050-084X.
van der Klaauw AA, Croizier S, Mendes de Oliveira E, Stadler LKJ, Park S, Kong Y, Banton MC, Tandon P, Hendricks AE, Keogh JM, Riley SE, Papadia S, Henning E, Bounds R, Bochukova EG, Mistry V, O'Rahilly S, Simerly RB, , , Minchin JEN, Barroso I, Jones EY, Bouret SG, Farooqi IS. Human Semaphorin 3 Variants Link Melanocortin Circuit Development and Energy Balance. Cell [print-electronic]. 2019 Feb 2/7/2019; 176(4): 729-742.e18. PMID: 30661757, PMCID: PMC6370916, PII: S0092-8674(18)31623-4, DOI: 10.1016/j.cell.2018.12.009, ISSN: 1097-4172.
Herrick MK, Favela KM, Simerly RB, Abumrad NN, Bingham NC. Attenuation of diet-induced hypothalamic inflammation following bariatric surgery in female mice. Mol Med. 2018 Oct 10/24/2018; 24(1): 56. PMID: 30355312, PMCID: PMC6201532, PII: 10.1186/s10020-018-0057-y, DOI: 10.1186/s10020-018-0057-y, ISSN: 1528-3658.
Kamitakahara A, Bouyer K, Wang CH, Simerly R. A critical period for the trophic actions of leptin on AgRP neurons in the arcuate nucleus of the hypothalamus. J. Comp. Neurol [print-electronic]. 2018 Jan 1/1/2018; 526(1): 133-45. PMID: 28891045, PMCID: PMC6040218, DOI: 10.1002/cne.24327, ISSN: 1096-9861.
Bedenbaugh MN, Brener SC, Maldonado J, Lippert RN, Sweeney P, Cone RD, Simerly RB. Organization of neural systems expressing melanocortin-3 receptors in the mouse brain: Evidence for sexual dimorphism. J Comp Neurol [print-electronic]. 2022 Nov; 530(16): 2835-51. PMID: 35770983, PMCID: PMC9724692, DOI: 10.1002/cne.25379, ISSN: 1096-9861.
Luchsinger JR, Fetterly TL, Williford KM, Salimando GJ, Doyle MA, Maldonado J, Simerly RB, Winder DG, Centanni SW. Delineation of an insula-BNST circuit engaged by struggling behavior that regulates avoidance in mice. Nat Commun. 2021 Jun 6/11/2021; 12(1): 3561. PMID: 34117229, PMCID: PMC8196075, PII: 10.1038/s41467-021-23674-z, DOI: 10.1038/s41467-021-23674-z, ISSN: 2041-1723.
Sweeney P, Bedenbaugh MN, Maldonado J, Pan P, Fowler K, Williams SY, Gimenez LE, Ghamari-Langroudi M, Downing G, Gui Y, Hadley CK, Joy ST, Mapp AK, Simerly RB, Cone RD. The melanocortin-3 receptor is a pharmacological target for the regulation of anorexia. Sci Transl Med. 2021 Apr 4/21/2021; 13(590): PMID: 33883274, PMCID: PMC9022017, PII: 13/590/eabd6434, DOI: 10.1126/scitranslmed.abd6434, ISSN: 1946-6242.
Biddinger JE, Lazarenko RM, Scott MM, Simerly R. Leptin suppresses development of GLP-1 inputs to the paraventricular nucleus of the hypothalamus. Elife. 2020 Nov 11/18/2020; 9: PMID: 33206596, PMCID: PMC7673779, PII: 59857, DOI: 10.7554/eLife.59857, ISSN: 2050-084X.
van der Klaauw AA, Croizier S, Mendes de Oliveira E, Stadler LKJ, Park S, Kong Y, Banton MC, Tandon P, Hendricks AE, Keogh JM, Riley SE, Papadia S, Henning E, Bounds R, Bochukova EG, Mistry V, O'Rahilly S, Simerly RB, , , Minchin JEN, Barroso I, Jones EY, Bouret SG, Farooqi IS. Human Semaphorin 3 Variants Link Melanocortin Circuit Development and Energy Balance. Cell [print-electronic]. 2019 Feb 2/7/2019; 176(4): 729-742.e18. PMID: 30661757, PMCID: PMC6370916, PII: S0092-8674(18)31623-4, DOI: 10.1016/j.cell.2018.12.009, ISSN: 1097-4172.
Herrick MK, Favela KM, Simerly RB, Abumrad NN, Bingham NC. Attenuation of diet-induced hypothalamic inflammation following bariatric surgery in female mice. Mol Med. 2018 Oct 10/24/2018; 24(1): 56. PMID: 30355312, PMCID: PMC6201532, PII: 10.1186/s10020-018-0057-y, DOI: 10.1186/s10020-018-0057-y, ISSN: 1528-3658.
Kamitakahara A, Bouyer K, Wang CH, Simerly R. A critical period for the trophic actions of leptin on AgRP neurons in the arcuate nucleus of the hypothalamus. J. Comp. Neurol [print-electronic]. 2018 Jan 1/1/2018; 526(1): 133-45. PMID: 28891045, PMCID: PMC6040218, DOI: 10.1002/cne.24327, ISSN: 1096-9861.