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SELECTBIO Conferences Cancer Immunotherapy & Biofluid Biopsies 2016

Louis Messina's Biography



Louis Messina, Professor and Chief Division od Vascular and Endovascular Surgery, Vice Chair Department of Surgery, University of Massachusetts Medical School

Traditionally our lab focused on the cellular and molecular mechanisms that regulate collateral artery enlargement towards a long-term goal develop molecular therapies to increase collateral artery enlargement. We are in the early stage of a Phase 1 clinical trial of a therapy that increases nitric oxide bioavailability in order to increase pain-free walking distance in people who suffer from intermittent claudication. Obesity will soon replace smoking and the most common cause of preventable deaths. Thus, a second focus of our lab is to understand how hypercholesterolemia, a metabolic disorder common in obese people, increases cancer risk of experimental colorectal cancer. In search of this mechanism we have identified a new mechanism that regulates innate immunity against cancer. This is caused by hypercholesterolemia-induced oxidant stress of hematopoietic stem cells that impairs their differentiation towards terminally differentiated innate immune cells that comprises immuno-surveillance against cancer.

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Hypercholesterolemia Increases Colon Cancer Risk by a Tet1-dependent Reduction of Hematopoietic Stem Cell differentiation towards NKT and ?dT cells: Potential Novel Immunotherapy

Wednesday, 2 November 2016 at 16:30

Add to Calendar ▼2016-11-02 16:30:002016-11-02 17:30:00Europe/LondonHypercholesterolemia Increases Colon Cancer Risk by a Tet1-dependent Reduction of Hematopoietic Stem Cell differentiation towards NKT and ?dT cells: Potential Novel ImmunotherapyCancer Immunotherapy and Biofluid Biopsies 2016 in Boston, USABoston, USASELECTBIOenquiries@selectbiosciences.com

Obesity will soon surpass smoking as the most preventable cause of cancer. Hypercholesterolemia, a common comorbidity in obese people, has been shown to increase cancer risk, especially colorectal cancer. However, the mechanism by which hypercholesterolemia, or any metabolic disorder, increases cancer risk remains unknown.  In this study, we show that hypercholesterolemia increases the incidence and pathological severity of colorectal neoplasia in two independent mouse models by inducing an oxidant-stress dependent increase in miR101c that downregulates Tet1 in hematopoietic stem cells (HSCs) which in turn reduces the expression of genes critical to natural killer T cell (NKT) and ?dT cell differentiation. These effects reduce the number and function of terminally differentiated NKT and ??T cells in the thymus, the colon submucosa and during early tumorigenesis.  These results suggest a new mechanism by which a metabolic disorder induces epigenetic mechanisms that reduce lineage priming of HSCs towards immune cells and thereby compromises immunosurveillance against cancer.


Add to Calendar ▼2016-11-01 00:00:002016-11-02 00:00:00Europe/LondonCancer Immunotherapy and Biofluid Biopsies 2016Cancer Immunotherapy and Biofluid Biopsies 2016 in Boston, USABoston, USASELECTBIOenquiries@selectbiosciences.com