EDUCATION AND TRAINING

Ph.D., University of California, Berkeley, Zoology

Postdoctoral: Albert Einstein College of Medicine, Department of Anatomy; University of Minnesota, Department of Anatomy

OFFICE ADDRESS

Seattle VA Puget Sound Health Care System (151)
1660 South Columbian Way
UW Mailbox 358280
Seattle, WA 98108


CURRENT RESEARCH INTERESTS

My research program focuses on the CNS regulation of food intake, body weight, and energy balance by hormones such as insulin and leptin. These hormones, which are present in blood in direct proportion to body fat mass, have profound anorexic effects when they enter the brain, where they alter the transcription, synthesis, and secretion of peptides (such as neuropeptide Y and melanocortins) in feeding-related neural circuits of the hypothalamus and brainstem. Recent work has focused on the interaction of leptin with the satiety action of peptides such as CCK and GLP-1 produced in the intestines during a meal. These gut peptides signal to the brainstem via the vagus nerve and regulate meal size by causing satiety, thereby resulting in meal termination. In the presence of leptin, these satiety signals to the brain are more effective, resulting in smaller meals. We have used immunocytochemistry, situ hybridization, retrograde axonal transport, confocal microscopy, and laser capture microdissection to identify the neuronal cell types, peptide receptors and circuits that participate in regulating meal size by the action of leptin in the hypothalamus and brainstem and, in particular, the interaction of leptin and gut satiety signals to the hindbrain. The goal of this research is to understand brain mechanisms that regulate food intake and body weight and how these mechanisms are altered in diabetes and obesity.


REPRESENTATIVE PUBLICATIONS

Schwartz MW, Seeley RJ, Campfield LA, Burn P, Baskin DG: Identification of targets of leptin action in rat hypothalamus. J Clin Invest 98:1101-1106, 1996.

Schwartz MW, Seeley RJ, Weigle DS, Campfield LA, Burn P, Baskin DG:  Leptin increases hypothalamic proopiomelanocortin mRNA expression in the rostral arcuate nucleus. Diabetes 46:2119-2113, 1997.

Baskin DG, Seeley RJ, Kuijper JL, Lok S, Weigle DS, Erickson JC, Palmiter RD, Schwartz MW:  Increased expression of mRNA for the long form of the leptin receptor in the hypothalamus is associated with leptin hypersensitivity and fasting. Diabetes 47:538-543, 1998.

Hahn TN, Breininger JF, Baskin DG, Schwatrz MW: Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nature Neurosci 1:271-272, 1998.

Baskin DG, Breininger JF, Schwartz MW:  Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamus. Diabetes 48:828-833, 1999.

Baskin DG, Schwartz MW, Seeley RJ, Woods SC, Porte D Jr, Breininger JF, Jonak J, Schaefer J, Krouse M, Burghardt C, Campfield LA, Burn P, Kochan JP:  Leptin receptor long form splice variant protein expression in neuron cell bodies of the brain and colocalization with neuropeptide Y mRNA in the arcuate nucleus. J. Histochem. Cytochem. 47:353-362, 1999.

Baskin DG, Breininger JF, Bonigut S, Miller MA:  Leptin binding in the arcuate nucleus is increased during fasting. Brain Res 828:154-158, 1999.

Schwartz MW, Woods SC, Porte Jr D, Seeley RJ, Baskin DG: Central nervous system control of food intake. Nature 404:661-671, 2000.

Grill HJ, Schwartz MW, Kaplan JM, Foxhall JS, Breininger J, Baskin DG:  Evidence that the caudal brainstem is a target for the inhibitory effect of leptin on food intake.  Endocrinology 143:239-246, 2002.

Niswender KD, Gallis B, Blevins JE, Corson M, Schwartz MW, Baskin DG:  Immunocytochemical detection of phosphatidylinositol 3-kinase activation by insulin and leptin.  J Histochem Cytochem 51:275-284, 2003.

Blevins JE, Eakin TJ, Murphy JA, Schwartz MW, Baskin DG: Oxytocin innervation of caudal brainstem nuclei activated by cholecystokinin.  Brain Res 993:30-41, 2003.

Blevins JE, Schwartz MW, Baskin DG:  Evidence that paraventricular nucleus oxytocin neurons link hypothalamic leptin action to caudal brainstem nuclei controlling meal size.  Am J Physiol Regul Intger Comp Physiol 287:87-96, 2004.

Porte D Jr, Baskin DG, Schwartz MW: Insulin signaling in the central nervous system: A critical role in metabolic homeostasis and disease from C. elegans to man.  Diabetes 54:1264-1276, 2005.

Morton GJ, Blevins JE, Niswender KD, Gelling RW, Rhodes CJ, Baskin DG, Schwartz MW:  Leptin action in the forebrain regulates the hindbrain response to satiety signals:  A mechanism linking body fat mass to the control of meal size. J Clin Invest 115:703-710, 2005.

Roth KA, Baskin DG: Enzyme-based fluorescence amplification for immunohistochemistry and in situ hybridization.  In: Molecular Morphology in Human Tissues: Techniques and Applications, Chapter 3.  G Hacker and R Tubbs, eds.  CRC Press LLC, Boca Raton, FL, 2005.

Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW^: Central nervous system control of food intake and body weight. Nature 443:289-295, 2006.

Baskin DG: Single-minded view of melanocortin signaling in energy homeostasis. Endocrinology, 147:4539-4541, 2006.

Williams DL, Baskin DG, Schwartz MW:  Leptin regulation of the anorexic response to glucagon like peptide-1 receptor stimulation. Diabetes 55:3387-3393, 2006.

Bastian LS, Baskin DG:  Techniques for immuno-laser capture microscopy of neurons for real time quantitative PCR.  In: Methods in Molecular Biology Volume 115: Immunocytochemical Methods and Protocols, 3^rd ed., C Oliver, M C Jamur, eds. Humana Press, In press.

Williams DL, Schwartz MW, Bastian LS, Blevins, JE, Baskin DG: Immunocytochemistry and laser capture microdissection for real time quantitative PCR identify neurons activated by interaction between leptin and cholecystokinin signaling to the hindbrain. J Histochem Cytochem. In press.