Faculty ProfilesKamran Atabai, MD
555 Mission Bay Blvd South
San Francisco, CA 94158
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.
Education and Training
|Location||Degree or Training||Specialty||Date|
|Harvard University||Fellowship||Pulmonary/Critical Care|
|University of California, San Francisco||Postdoctoral Studies||Graduate Division|
|University of California, San Francisco||Residency||School of Medicine - Internal Medicine|
Related Web Sites
Recent Articles (27)
Podolsky MJ, Gupta D, Ha A, Ta R, Khalifeh-Soltani A, McKleroy W, Datta R, Sheppard D, Atabai K. Cell Division Cycle 7-Kinase is a negative regulator of cell-mediated collagen degradation. Am J Physiol Lung Cell Mol Physiol. 2018 May 24.
Zhou Y, Horowitz JC, Naba A, Ambalavanan N, Atabai K, Balestrini J, Bitterman PB, Corley RA, Ding BS, Engler AJ, Hansen KC, Hagood JS, Kheradmand F, Lin QS, Neptune E, Niklason L, Ortiz LA, Parks WC, Tschumperlin DJ, White ES, Chapman HA, Thannickal VJ. Extracellular matrix in lung development, homeostasis and disease. Matrix Biol. 2018 Mar 08.
Michalski MN, Seydel AL, Siismets EM, Zweifler LE, Koh AJ, Sinder BP, Aguirre JI, Atabai K, Roca H, McCauley LK. Inflammatory bone loss associated with MFG-E8 deficiency is rescued by teriparatide. FASEB J. 2018 Feb 22; fj201701238R.
Long Z, Cao M, Su S, Wu G, Meng F, Wu H, Liu J, Yu W, Atabai K, Wang X. Inhibition of hepatocyte nuclear factor 1b induces hepatic steatosis through DPP4/NOX1-mediated regulation of superoxide. Free Radic Biol Med. 2017 Dec; 113:71-83.
Xie Y, Cifarelli V, Pietka T, Newberry EP, Kennedy SM, Khalifeh-Soltani A, Clugston R, Atabai K, Abumrad NA, Davidson NO. Cd36 knockout mice are protected against lithogenic diet-induced gallstones. J Lipid Res. 2017 Aug; 58(8):1692-1701.
Khalifeh-Soltani A, Gupta D, Ha A, Iqbal J, Hussain M, Podolsky MJ, Atabai K. Mfge8 regulates enterocyte lipid storage by promoting enterocyte triglyceride hydrolase activity. JCI Insight. 2016 Nov 03; 1(18):e87418.
Khalifeh-Soltani A, Ha A, Podolsky MJ, McCarthy DA, McKleroy W, Azary S, Sakuma S, Tharp KM, Wu N, Yokosaki Y, Hart D, Stahl A, Atabai K. a8ß1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism. Elife. 2016 04 19; 5.
Tharp KM, Khalifeh-Soltani A, Park HM, Yurek DA, Falcon A, Wong L, Feng R, Atabai K, Stahl A. Prevention of gallbladder hypomotility via FATP2 inhibition protects from lithogenic diet-induced cholelithiasis. Am J Physiol Gastrointest Liver Physiol. 2016 May 15; 310(10):G855-64.
Bhattacharya M, Sundaram A, Kudo M, Farmer J, Ganesan P, Khalifeh-Soltani A, Arjomandi M, Atabai K, Huang X, Sheppard D. IQGAP1-dependent scaffold suppresses RhoA and inhibits airway smooth muscle contraction. J Clin Invest. 2014 Nov; 124(11):4895-8.
Soki FN, Koh AJ, Jones JD, Kim YW, Dai J, Keller ET, Pienta KJ, Atabai K, Roca H, McCauley LK. Polarization of prostate cancer-associated macrophages is induced by milk fat globule-EGF factor 8 (MFG-E8)-mediated efferocytosis. J Biol Chem. 2014 Aug 29; 289(35):24560-72.
Khalifeh-Soltani A, McKleroy W, Sakuma S, Cheung YY, Tharp K, Qiu Y, Turner SM, Chawla A, Stahl A, Atabai K. Mfge8 promotes obesity by mediating the uptake of dietary fats and serum fatty acids. Nat Med. 2014 Feb; 20(2):175-83.
Lee TH, McKleroy W, Khalifeh-Soltani A, Sakuma S, Lazarev S, Riento K, Nishimura SL, Nichols BJ, Atabai K. Functional genomic screen identifies novel mediators of collagen uptake. Mol Biol Cell. 2014 Mar; 25(5):583-93.
Kudo M, Khalifeh Soltani SM, Sakuma SA, McKleroy W, Lee TH, Woodruff PG, Lee JW, Huang K, Chen C, Arjomandi M, Huang X, Atabai K. Mfge8 suppresses airway hyperresponsiveness in asthma by regulating smooth muscle contraction. Proc Natl Acad Sci U S A. 2013 Jan 08; 110(2):660-5.
Kudo M, Melton AC, Chen C, Engler MB, Huang KE, Ren X, Wang Y, Bernstein X, Li JT, Atabai K, Huang X, Sheppard D. IL-17A produced by aß T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction. Nat Med. 2012 Mar 04; 18(4):547-54.
Atabai K, Jame S, Azhar N, Kuo A, Lam M, McKleroy W, Dehart G, Rahman S, Xia DD, Melton AC, Wolters P, Emson CL, Turner SM, Werb Z, Sheppard D. Mfge8 diminishes the severity of tissue fibrosis in mice by binding and targeting collagen for uptake by macrophages. J Clin Invest. 2009 Dec; 119(12):3713-22.
Nandrot EF, Anand M, Almeida D, Atabai K, Sheppard D, Finnemann SC. Essential role for MFG-E8 as ligand for alphavbeta5 integrin in diurnal retinal phagocytosis. Proc Natl Acad Sci U S A. 2007 Jul 17; 104(29):12005-10.
Atabai K, Fernandez R, Huang X, Ueki I, Kline A, Li Y, Sadatmansoori S, Smith-Steinhart C, Zhu W, Pytela R, Werb Z, Sheppard D. Mfge8 is critical for mammary gland remodeling during involution. Mol Biol Cell. 2005 Dec; 16(12):5528-37.
Atabai K, Ishigaki M, Geiser T, Ueki I, Matthay MA, Ware LB. Keratinocyte growth factor can enhance alveolar epithelial repair by nonmitogenic mechanisms. Am J Physiol Lung Cell Mol Physiol. 2002 Jul; 283(1):L163-9.
Atabai K, Ware LB, Snider ME, Koch P, Daniel B, Nuckton TJ, Matthay MA. Aerosolized beta(2)-adrenergic agonists achieve therapeutic levels in the pulmonary edema fluid of ventilated patients with acute respiratory failure. Intensive Care Med. 2002 Jun; 28(6):705-11.
Burgel PR, Lazarus SC, Tam DC, Ueki IF, Atabai K, Birch M, Nadel JA. Human eosinophils induce mucin production in airway epithelial cells via epidermal growth factor receptor activation. J Immunol. 2001 Nov 15; 167(10):5948-54.
Geiser T, Atabai K, Jarreau PH, Ware LB, Pugin J, Matthay MA. Pulmonary edema fluid from patients with acute lung injury augments in vitro alveolar epithelial repair by an IL-1beta-dependent mechanism. Am J Respir Crit Care Med. 2001 May; 163(6):1384-8.