Research at the S. Arthur Localio Laboratory

Overview

The S. Arthur Localio Laboratory is a basic and translational research laboratory within the NYU Department of Surgery and Cell Biology. The main interests of our lab include pancreatic inflammation and carcinogenesis, acute and chronic liver disease, and basic cellular immunology.

Pancreatic Inflammation and Cancer

Pancreatic ductal carcinoma is the 4th most common cause of cancer death in the USA and is lethal in more than 95% of cases. Chronic pancreatic fibro-inflammation, known as chronic pancreatitis, is the most prevelant risk factor for the development of pancreatic cancer. Unlike most adenocarcinomas whose volume is comprised primarily of transformed cells, pancreatic cancer is composed mainly of fibro-inflammatory stromal elements interspersed with islands of neoplastic epithelium. Recent evidence suggests that pancreatic tumor stroma affects both cancer progression and disease outcome. In particular, by releasing nutrient growth factors into the tumor microenvironment, the stromal component of pancreatic cancer has been closely linked to both tumor growth and invasiveness. However, the activators of stromal inflammation and fibrosis and the precise biochemical interplay between inflammatory cells and transformed epithelial cells remain poorly understood. Hence the delineation of the regulatory circuitry responsible for both expansion of the inflammatory pancreatic cancer stroma and its mechanism of cross-talk with neoplastic ductal epithelial cells has the potential to greatly expand our capabilities for therapeutic intervention.

Our lab is interested in numerous aspects of the biology of the tumor microenvironment that influences epithelial mutagenesis. Our recent investigations have examined the role of novel pattern recognition receptors, intra-tumoral dendritic cells, and novel T cell subpopulations. We have also examined the role of novel chemokines and signaling molecules in mediating epithelial-stromal cross-talk. Additionally, we have an emerging vaccine program where we immunize mice genetically predisposed to develop pancreatic cancer with tumor-derived proteins linked to novel immune adjuvants. We have an important effort in translating our discoveries to the clinic.

Chronic Liver Disease

Liver fibrosis is one of the most significant public health concerns worldwide. Liver fibrosis is the most common cause of primary liver cancer. Numerous conditions can result in liver fibrosis including hepatitis virus infection, alcohol abuse, and non-alcoholic steatohepatitis (NASH). The cellular and molecular pathogeneses of liver fibrosis are incompletely understood. After liver injury from viruses, toxins, or metabolic disorders, a complex inflammatory cascade results in the induction of normally quiescent hepatic stellate cells (HSC) which deposit an extracellular matrix that eventually replaces the normal hepatic parenchyma. The induction of HSC is thought to be the result of stimulation by a combination of pro-inflammatory chemokines (MIP1a, MIP-1b, CCL2, CCL11, CCL22 and CCL6) and cytokines (TNF-a, MCP-1, TGF-b, IL-4, IL-5, IL-6, IL-13 and IL-21). However, the precise interplay of cell types that contribute to HSC activation is uncertain. Our lab is interested in the cellular and biochemical mediators of chronic liver injury leading to fibrosis.

We have investigated the role of diverse antigen presenting cells in mediating chronic liver inflammation leading to hepatocellular injury and fibrosis. We are also interested in studying novel receptors on immune cells that link inflammatory responses in the liver to environmental stimuli and their relevance to acute and chronic liver injury.

Basic Cellular Immunology

Our lab has discovered novel T cell subsets recruited to the inflamed pancreas and novel dendritic cell subsets in the liver. We have investigated the effects of intracellular lipids on basic dendritic cell function and have also investigated the role of lipids in dendritic cell development from bone marrow precursors.