Kamran Atabai, MD

Associate Professor
Department of Medicine
+1 415 514-1159
Research Description: 

The main focus of my laboratory is examining the role of the extracellular matrix in regulating metabolism, tissue remodeling, and smooth muscle function as these processes relate to cardiovascular disease. My laboratory has several different areas of investigation that have been generated from studies related to this primary focus. (1) We have been investigating the role of the extracellular matrix in coordinating fatty acid uptake and promoting development of obesity and insulin resistance. (2) We have been examining the role of cell-mediated collagen turnover in regulating the severity of tissue fibrosis using both mouse models of fibrosis and RNAi based whole genome screen of collagen turnover in Drosophila phagocytes. (3) We have been examining the role of the extracellular matrix in regulating inflammation and proliferation in both airway and vascular smooth muscle. In airway smooth muscle, we have been exploring a pathway by which the integrin ligand Mfge8 prevents cytokine-induced increases in calcium sensitivity thereby preventing airway obstruction in models of allergic airway disease. In vascular smooth muscle, we have been focused on understanding the mechanisms by which the matrix promotes neointimal hyperplasia and how these effects regulate vascular disease such as vascular stenosis post percutaneous angioplasty and bypass grafting and pulmonary hypertension.

Specific projects currently being actively pursued in the lab are as follows:

1). Understanding the systemic pathways that control absorption of dietary fats and deposition of neutral lipids in peripheral stores. Our goals in this project are to understand what factors systemically regulate lipid metabolism and how these pathways interact with glucose and lipid regulation by insulin. We are particular interested in exploring the link between fatty acids and insulin resistance.

2). Investigating the role of cell-mediated collagen uptake and degradation in regulating tissue fibrosis. The replacement of normal tissue architecture with collagen-rich fibrotic tissue causes significant morbidity and mortality in multiple organ systems. We have recently shown that macrophage-mediated resorption of fibrillar collagens is important in limiting the severity of lung fibrosis after injury. The goal of this project is to delineate the intracellular pathways that regulate collagen turnover with the ultimate goal of targeting them for treatment of established fibrotic disease.

3). Inhibiting activation of RhoA to prevent airway constriction in asthma. Bronchoconstriction is the main cause of shortness of breath in asthma and occurs in large part due to an increase in calcium sensitivity induced by allergic inflammation of airway smooth muscle. We have recently identified a pathway that specifically inhibits the ability of cytokines released in the asthmatic airway to increase calcium sensitivity. We are now focused on comprehensively investigating the molecular pathway that mediates these effects with the ultimate goal of targeting them to prevent airway obstruction in asthma as well as to better understand the mechanisms that regulate calcium sensitivity in smooth muscle beds throughout the body.

Primary Thematic Area: 
Tissue / Organ Biology & Endocrinology
Secondary Thematic Area: 
Immunology
Research Summary: 
Extracellular matrix regulation of metabolism, pulmonary disease, and cardiovascular disease

Websites

Publications: 

PTP1B mediates the inhibitory effect of MFGE8 on insulin signaling through the β5 integrin.

The Journal of biological chemistry

Datta R, Mukherjee D, Podolsky MJ, Yang CD, Alba DL, Singh S, Arnold TD, Koliwad S, Lizama CO, Atabai K

BCL-2 Modulates IRE1α Activation to Attenuate ER Stress and Pulmonary Fibrosis.

American journal of respiratory cell and molecular biology

Jourdan Le Saux C, Ho TC, Brumwell AM, Kathiriya JJ, Wei Y, Hughes JB, Garakani K, Atabai K, Auyeung VC, Papa FR, Chapman HA

Genome-wide screens identify SEL1L as an intracellular rheostat controlling collagen turnover.

bioRxiv : the preprint server for biology

Podolsky MJ, Kheyfets B, Beigh AH, Yang CD, Valenzuela CL, Datta R, Wolters PJ, McManus MT, Qi L, Atabai K

Radial glia promote microglial development through integrin α V β 8 -TGFβ1 signaling.

bioRxiv : the preprint server for biology

McKinsey GL, Santander N, Zhang X, Kleemann K, Tran L, Katewa A, Conant K, Barraza M, Waddell K, Lizama C, La Russa M, Koo HJ, Lee H, Mukherjee D, Paidassi H, Anton ES, Atabai K, Sheppard D, Butovsky O, Arnold TD

MFGE8 inhibits insulin signaling through PTP1B.

bioRxiv : the preprint server for biology

Datta R, Podolsky MJ, Yang CD, Alba DL, Singh S, Koliwad S, Lizama CO, Atabai K