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Bradford Lowell, MD,Ph.D.

Professor of Medicine

Beth Israel Deaconess Medical Center
99 Brookline Ave., RN-325-D
One Joslin Place
Boston, MA 02215
Telephone: 617-667-5954
Fax: 617- 667-2927
Email: blowell@bidmc.harvard.edu
Predocs: 0 Postdocs: 7 Completed PhD's: 1

  

The Lowell Lab is an Integrative Molecular Physiology group which utilizes genetic engineering techniques in mice to study central and peripheral pathways controlling energy balance.

  1. Functional Neurocircuitry of Body Weight Control.
    2. Neuroanatomical mapping studies have identified neurocircuits which may be important in regulating food intake and energy expenditure. We are using conditional, neuron-specific gene targeting methods to determine the functional importance of these neurocircuits in controlling body weight. Techniques being utilized include BAC transgenesis, neuron-specific gene knockouts, and neuron-specific gene reactivations.
  2. Uncoupling Protein (UCP)-Mediated Mitochondrial Proton Leak.
    3. UCP2 negatively regulates insulin secretion and upregulation of UCP2 in obesity causes pancreatic b-cell dysfunction. Superoxide stimulates UCP2-mediated proton leak and this superoxide – UCP2 pathway contributes importantly to the development of beta cell dysfunction in type 2 diabetes. We are now investigating the role of UCP2 in negatively regulating glucose-sensing in the brain.
  3. Mechanisms of Diet-Induced Thermogenesis.
    4. bARs and the sympathetic nervous system are necessary for diet-induced thermogenesis and this pathway is critical in the defense against diet-induced obesity. Using mice genetically engineered to lack bARs as the genetic background, we are transgenically re-expressing bARs in candidate thermogenic target tissues and then assessing effects on diet-induced thermogenesis and diet-induced obesity.

 

References:

  • Balthasar N, Coppari R, McMinn J, Liu SM, Lee CE, Tang V, Kenny CD, McGovern RA, Chua SC Jr*, Elmquist JK*, Lowell BB*. Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 2004; 42:983-91.
  • Coppari R, Masumi Ichinose, Lee CE, Pullen AE, Kenny CD, McGovern RA, Tang V, Liu SM, Ludwig T, Chua Jr. SC*, Lowell BB*, Elmquist JK*. The hypothalamic arcuate nucleus: A key site for mediating leptin's effects on glucose homeostasis and locomotor activity. Cell Metabolism 2005; 1:63-72.
  • Balthasar N, Dalgaard LT, Lee CE, Yu J, Funahashi H, Williams T, Ferreira M, Tang V, McGovern RA, Kenny CD, Christiansen LM, Edelsttein E, Choi B, Boss O, Aschkenasi C, Zhang CY, Mountjoy M, Kishi T, Elmquist*, Lowell BB*. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 2005; 123:493-505.
  • Zigman JM, Nakano Y, Coppari R, Balthasar N, Marcus JN, Lee CE, Jones JE, Deysher AE, Waxman AR, White RD, Williams TD, Lachey JL, Seeley RJ, Lowell BB*, Elmquist JK*. Mice lacking ghrelin receptors resist the development of diet-induced obesity. J Clin Invest 2005; 115:3564-72.
  • Dhillon H, Zigman JM, Ye C, Lee CE, McGovern RA, Tang V, Kenny CD, Christiansen LM, White RD, Edelstein EA, Coppari R, Balthasar N, Cowley MA, Chua Jr. SC*, Elmquist JK*, Lowell BB*. Leptin directly activates SF1 neurons in the ventromedial hypothalamus and this action by leptin is required for normal body weight homeostasis. Neuron 2006; 49:191-203.