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INDIVIDUAL RESEARCHER

Patricia G Grasso , Ph.D.
Associate Professor
e-mail: GrassoP@mail.amc.edu

Phone: 25639
Fax: 26303

Education

1984 - Ph.D. from Geotgetown University School of Medicine


Current Research

Our laboratory is currently involved in (1) describing the signal transduction pathways activated by biologically active synthetic peptide analogs of leptin, and (2) improving the pharmacokinetics and pharmacodynamics of [D-Leu-4]-OB3, the most  potent of the biologically active leptin-related synthetic peptides developed thus far. 



Research Interests

1.  Drug development and delivery

2.  Diabetes

3.  Obesity 



Research Summary

 Dr. Grasso's major area of investigation is focused on the molecular mechanisms by which synthetic peptide analogs of leptin (OB protein) regulate energy expenditure and glucose homeostasis. These efforts utilize both in vivo and in vitro model systems, and a synthetic peptide approach. Our laboratory has recently shown that peripheral administration -- intraperitoneal, nasal, and oral -- of synthetic peptides representing restricted domains of mouse leptin, to genetically obese diabetic leptin-deficient ob/ob mice and leptin-resistant db/db mice, and to streptozotocin-induced diabetic Swiss Webster mice reduces food intake, body weight gain, and serum glucose levels, and increases tissue sensitivity to insulin. These observations indicate that the entire leptin molecule is not required for restoration of energy balance and glycemic regulation, and that smaller peptides encompassing one or more active sites of leptin may contain sufficient information to (a) compensate for endogenous leptin or leptin receptor deficiencies and transport, (b) induce satiety, (c) stimulate weight loss, and (d) regulate blood glucose levels. The effectiveness of our peptides in these mouse models suggests that development of leptin-related peptide analogs or nonpeptide mimetics of leptin may have potential application to the treatment of at least some forms of human obesity, a syndrome characterized by hyperphagia, hyperglycemia, hyperinsulinemia, thyroid dysfunction, and reproductive insufficiency. More recently, we have shown that the most active of these analogs, [D-Leu-4]-OB3, through its insulin sensitizing action, may also be useful in the treatment of insulin-deficient (T1DM) and insulin-resistant (T2DM) diabetes mellitus in the absence of an obese background.



PubMed Publications

  1. Waldrop, MA, Leinung MC, Lee DW, Grasso P. Intranasal delivery of mouse [D-Leu-4]-OB3, a synthetic peptide amide with leptin-like activity, improves energy balance, glycemic control, insulin sensitivity, and bone formation in leptin-resistant C57BLK/6-m db/db mice. Diabetes, Obesity and Metabolism 12: 871-875, 2010.


  2. Grasso P. Novel approaches to the treatment of obesity and type 2 diabetes mellitus: bioactive leptin-related synthetic peptide analogs. Recent Patents on Endocrine, Metabolic & Immune Drug Discovery 5:163-175, 2011.


  3. Leinung MC, Grasso P. [D-Leu-4]-OB3, a synthetic peptide amide with leptin-like activity, augments the effects of orally delivered exenatide (Byetta®) and pramlintide acetate (Symlin®) on energy balance and glycemic control in insulin-resistant C57BLK’6-m db/db mice. Regulatory Pept. 179: 33-38. 2012.


  4. Novakovic ZM, Leinung MC, Grasso P. [D-Leu-4]-OB3, an orally bioavailable leptin-related synthetic peptide insulin sensitizer: a study comparing the efficacies of [D-Leu-4]-OB3 and metformin on energy balance and glycemic regulation in insulin-deficient male Swiss Webster mice. Peptides 43: 167-173, 2013


  5. Lin H-Y, Yang S-H, Tang H-Y, Cheng G-Y, Davis PJ, Grasso P. Biologically active leptin-related synthetic peptides activate STAT3 via phosphorylation of ERK 1/2 and PI-3K. Peptides 57: 95-100, 2014.