Dr. Linda Gutierrez

• 1980-1987 | MD Universidad de Carabobo, Venezuela
• 1990-1993 | Anatomic-Pathology Specialist Universidad Central de Venezuela
• 1994-1998 | Post-doctoral Fellow Yale University

• Inflammatory bowel disease
• Colorectal, breast and prostate cancers
• Angiogenesis
• Apoptosis

More than 1.4 million Americans suffer from inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease. Patients with IBD have a high risk of developing colorectal cancer. These chronic and idiopathic diseases seriously affect the quality of life of the patients and represent a significant burden on the country’s health care system.

Dr. Gutierrez is investigating the role of thrombospondin 1 (TSP-1) in the development of these diseases and testing specific sequences of this protein as a novel and safe therapy for IBD and colorectal cancer. Thrombospondin 1 (TSP-1) is a powerful antiangiogenic with diverse roles in physiological and pathological events. This 450Kd glycoprotein interacts with members of different pathways regulating cell migration, proliferation and apoptosis.

These are the on-going projects currently expanded by NIH support:

Project 1: TSP-1 In Induced Acute Colitis

The role of TSP-1 is being investigated by using the dextran sodium sulfate (DSS)-induced colitis in order to recognize its specific molecular targets in colonic inflammation and to design new therapeutic strategies for treating IBD.

Project 2: TSP-1 In Chronic Colitis and IBD-Related Dysplasia

The full understanding of the cellular processes occurring when a normal cell changes to malignant is fundamental for cancer prevention. We are evaluating the genetic pathways associated with TSP-1 on the development of IBD-related dysplasia and mapping the genetic pathways associated with this protein during the development of colitis-related carcinogenesis.

Project 3: Therapeutics Effects And Mechanisms Mediated By TSP-1 Derived Peptides In IBD

In collaboration with Dr. Jack Lawler (Harvard University, Boston, MA), Dr. Jun Ling (The Commonwealth Medical College, Scranton, PA) and Abbott Laboratories (Chicago, IL), peptides derived from specific sequences of the type 1 repeats of TSP-1 are being tested. By using microarray gene technology and proteomics analyses their relevant cell signaling pathways and their relationship with inflammation, proliferation, apoptosis and angiogenesis are being evaluated.

Project 4: Environmental Factors In Inflammatory Bowel Disease

Environmental factors are suspected of triggering IBD in people with genetic susceptibility. However, no single factor has been consistently proven to be the primary cause. For unknown reasons, IBD is more common in people who live in northern climates and developed countries compared to those who live in southern climates or developing countries. We are collaborating with pathologists in Venezuela, evaluating biopsies from patients suffering of IBD. Venezuela as many other underdeveloped countries has a low incidence of Crohn’s Disease and ulcerative colitis.

Project 5: TSP-1 and the Intestinal Microflora

Some studies indicate that IBD may be caused for changes in the normal intestinal flora, in which pathogenic strains overcome normal bacteria invading the intestine and initiating the inflammatory process. In a research collaboration directed by Dr. Kenneth Pidcock, associate professor in Biology, the role of TSP-1 in the intestinal bacterial flora is being investigated.

• BIO 298 HHMI Super Labs Animal Models
• BIO 352 Pathophysiology
• BIO 398 Cancer Biology
• BIO 398-Biomedicine
• BIO 398- Medical Ethics

1. Lopez-Dee Z, Shittur SV, Patel B, Stanton R, Wakeley M, et al. (2012) Thrombospondin-1 type 1 repeats in a model of inflammatory bowel disease: Transcript profile and therapeutic effects. PLoS One 7(4):e34590.
2. Gutierrez LS. Dr. Morris Pollard. (2011) Nutr Cancer 263(8):1367-8
3. Lopez-Dee Z, Pidcock K, Gutierrez LS. (2011) Thrombospondin-1: multiple paths to inflammation. Mediators Inflamm 296069.
4. Punekar S, Zak S, Kalter VG, Dobransky L et al. (2008) Thrombospondin 1 and its mimetic peptide ABT-510, decrease angiogenesis and inflammation in a murine model of inflammatory bowel disease. Pathobiology 75(1): 9-21.
5. Zak S, Treven J, Nash N, Gutierrez LS. (2008) Lack of thrombospondin-1 increases angiogenesis in a model of chronic inflammatory bowel disease. Int J Colorectal Dis 23(3): 297-304.
6. Gutierrez LS. (2008)The role of thrombospondin 1 on intestinal inflammation and carcinogenesis. Biomark Insights (3) 171-178
7. Gutierrez LS, Noria F, Finol H, Sun L, Castellino F, Pollard M. (2005)Fas ligand expression and its correlation with apoptosis and proliferation in Lobund-Wistar prostate carcinomas. Pathobiology 72(5):260-8.
8. Suckow M, Gutierrez LS, Risatti C, Wolter W, Taylor R, Pollard M, Navari RM, Castellino F, Paoni NF. (2004) The anti-ischemia agent ranolazine promotes the development of intestinal tumors in Apc Min+ mice. Cancer Lett 209: 165-169
9. Gutierrez LS, Suckow M, Lawler J, Ploplis VA, Castellino FJ. (2003)Thrombospondin-1 Is A Regulator Of Adenoma Growth And Carcinoma Progression In The ApcMin+ Mouse. Carcinogenesis 24: 199-207.
10. Paoni N, Feldman M, Gutierrez LS, Ploplis V, Castellino FJ. (2003)Transcriptional profiling of the Transition from Normal Intestinal Epithelia to Adenomas and Carcinomas in the ApcMin+ Mouse. Physiol Genomics 15(3): 228-35.