Ruben Rene Gonzalez, Ph.D. Research Assistent Professor, Department of Microbiology, Biochemisty, & Immunology Morehouse School of Medicine Email: rgonzalez@msm.edu Office Phone: (404) 752-1581 Fax: (404) 752-1179

Research Interests

The protein Leptin, although mainly secreted by the fat tissue and primarily known for its roles in obesity and reproduction, is considered to be responsible for the long recognized causal link between obesity and the increased risk of cancer. Leptin, an essential upstream factor for endometrial receptivity/implantation, induces the expression of angiogenic, proliferative and anti-apoptotic factors. Leptin-induced effects could be linked to AKT1/NFkB and bcl-2 protein and regulated in part by IL-1 signaling. Our laboratory has designed, produced and tested some novel inhibitors (leptin peptide receptor antagonists, LPrA and pegylated derivatives, PEG-LPrAs) of leptin signaling. PEG-LPrAs (half-lives = 55 hours) abrogate the leptin-induced signaling pathways (JAK2/STAT3, MEK-1/MAPK/ERK 1/2 and PI-3K/AKT1/mToR) involved in the increased levels of VEGF/VEGFR2; LIF/LIFR; IL- 1/IL-1R tI, ß3 integrin and cyclin D1. Disruption of leptin signaling by LPrAs significantly prevents the establishment and reduces the growth of mammary tumors and metastasis in mice. LPrA treatment could be an innovative adjuvant for prevention/treatment of breast and other cancer types. Our investigations are equally important for many processes where leptin plays a role, i.e. , fertility regulation, endometriosis, arthritis, diabetes, etc.

Selected Publications

1. Gonzalez RR, Simon C, Caballero-Campo P, et al . (1999). Leptin and reproduction. Hum. Reprod. Update 6 (3): 290-300.

2. Gonzalez RR, Caballero-Campo P, Jasper M et al . (2000). Leptin and leptin receptor are expressed in the human endometrium. Leptin secretion is differentially regulated by human blastocyst in endometrial epithelial cells. J. Clin. Endocrinol. Metab. 85 (12):4883-4888.

3. Gonzalez RR, Rueda, BR, Ramos MP et a l. (2004). Leptin induced increase in leukemia inhibitory factor and its receptor by human endometrium is partially mediated by interleukin 1 receptor signaling. Endocrinology 145 (8):3850-3857 [Featured paper on MDlinx, July 20th, 2004 / www. mdlinx.com].

4. Ramos MP, Rueda BR, Leavis, P, Gonzalez RR. (2005). Leptin serves as an upstream activator of an obligatory signaling cascade in the embryo-implantation process. Endocrinology 146 (2):694-701, Epub 2004 Nov 11

5. Gonzalez RR, Cherfils S, Escobar M, et al . (2006) Leptin signaling promotes the growth of mammary tumors and increases the expression of vascular endothelial growth factor (VEGF) and its receptor type two (VEGF-R2). J. Biol. Chem. 281 (36): 26320-26328. Epub 2006 July 6 [Highlighted paper on Nature Reviews Cancer 8 (6): 580, 2006].