Rudolph Leibel, MD

Dr. Leibel’s research relates to the molecular genetics of control of body weight in rodents and humans, the bioenergetics of body weight regulation in humans, and the role of leptin in these processes, including the metabolic and behavioral responses to maintenance of a reduced body weight. He and his associates are using human stem cell derived hypothalamic neurons and islet beta cells to elucidate the molecular physiology of obesity and diabetes.  

The Leibel laboratory is interested in the molecular physiology and genetics of body weight regulation and diabetes in humans and rodents. Dr. Leibel and his associates have cloned and characterized a number of genes in the pathways regulating bodyweight and modifying diabetes susceptibility. We participated in the molecular cloning and characterization of the leptin and leptin receptor genes and have continued to pursue the molecular physiology of the “leptin axis” in body weight regulation, recently focusing on the molecular physiology of the FTO locus in mice and humans. We have shown that genetically implicated non-coding sequences in intron 1 are affecting the expression of a component of the primary cilium, RPGRIP1L. During the past decade, Dr. Leibel has worked with associates at Columbia to develop techniques for creating iPS cells from somatic cells of patients segregating for monogenic forms of diabetes and obesity. They have succeeded in making such cells from MODY, Wolfram, T1D, Bardet-Biedl and Prader-Willi patients, and in showing that beta cells and neurons derived from these iPSCs cells recapitulate the anticipated seminal phenotypes of the patients from whom they were derived. Most recently they have been examining, in mice, the effects of transient metabolic perturbations in early life on subsequent risk of hyperphagic obesity.  

Key and Recent Publications

  • Leibel RL. Role of adipocyte geometry in eating behavior. Science. 1978 Jun 30;200(4349):1504-5
  • Leibel, RL, Rosenbaum, M, and Hirsch, J. Changes in energy expenditure resulting from altered body weight. New England Journal of Medicine 332.10 (1995): 621-628.
  • Burnett LC, LeDuc CA, Sulsona CR, Paull D, Rausch R, Eddiry S, Martin Carli JF, Morabito MV, Skowronski AA, Hubner G, Zimmer M, Wang L, Day R, Levy B, Fennoy I, Dubern B, Poitou C, Clement K, Butler MG, Rosenbaum M, Salles JP, Tauber M, Driscoll DJ, Egli D, and Leibel RL. Deficiency in prohormone convertase PC1 impairs prohormone processing in Prader-Willi Syndrome. The Journal Clin Invest. 2017;127(1):293-305. 
  • Wang, L., Meece, K., Williams, D. J., Lo, K. A., Zimmer, M., Heinrich, G., ... & Leibel, R. L. (2015). Differentiation of hypothalamic-like neurons from human pluripotent stem cells.  The Journal Clin Invest., 125(2), 796-808.
  • Wang, Liheng, Yang Liu, George Stratigopoulos, Sunil Panigrahi, Lina Sui, Yiying Zhang, Charles A Leduc, Hannah J Glover, Maria Caterina De Rosa, Lisa C Burnett, Damian J Williams, Linshan Shang, Robin Goland,Stephen H Tsang, Sharon Wardlaw, Dieter Egli, Deyou Zheng, Claudia A Doege, Rudolph L Leibel. Bardet-Biedl syndrome proteins regulate intracellular signaling and neuronal function in patient-specific iPSC-derived neurons. J Clin Invest. 2021 Apr 15;131(8):e146287.