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While much is known about the molecular basis of hypothalamic control in mammalian energy homeostasis, neural circuit plasticity including changes in neural cell numbers has only recently been implicated in body weight regulation. We want to decipher the mechanistic underpinnings of long-term changes in body weight set points by exploring plastic changes in the brain circuits that control feeding.

We have previously shown that exogenous induction of hypothalamic cell proliferation is associated with weight loss. We also have demonstrated that cells proliferate on an ongoing basis in the adult hypothalamus, even in the absence of external cues such as growth factor administration. We are currently investigating the role of these constitutively born cells in energy homeostasis by employing in vivo cell ablation approaches in conjunction with electrophysiological and ultrastructural studies.

The long-term goal of my lab is to mechanistically understand why some humans can maintain their body weights strikingly constant over most of their adult lives while others are confronted with gradual or abrupt increases in fat mass. Our studies may thus provide new insight in the etiology of obesity and ultimately help to develop new strategies for the prevention and treatment of obesity-related diseases.