Kamran Atabai, MD
Professor
Medicine
School of Medicine

(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.

• Genome-wide screens identify SEL1L as an intracellular rheostat controlling collagen turnover.
  bioRxiv : the preprint server for biology 2023 Podolsky MJ, Kheyfets B, Pandey M, Beigh AH, Yang CD, Lizama Valenzuela C, Datta R, Wolters PJ, McManus M, Qi L, Atabai K
• Radial glia promote microglial development through integrin αVβ8 -TGFβ1 signaling.
  bioRxiv : the preprint server for biology 2023 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 …
• MFGE8 inhibits insulin signaling through PTP1B.
  bioRxiv : the preprint server for biology 2023 Datta R, Podolsky MJ, Yang CD, Alba DL, Singh S, Koliwad S, Lizama CO, Atabai K
• Tu1246 CROHN'S DISEASE STRICTURE MATRISOME ANALYSIS REVEALS THE ANTI-FIBROTIC ACTIVITY OF MILK-FAT GLOBULE-EPIDERMAL GROWTH FACTOR 8 (MFGE8).
  Gastroenterology 2023 Sinan Lin, Jie Wang, Pranab Mukherjee, Ren Mao, Gail A. West, Doug Czarnecki, Shuai Zhao, Quang Tam Nguyen, Jyotsna Chandra, Thi Hong Nga Le, Dina Dejanovic, Minhu Chen, Stefan D. Holubar, Mitch Olman…
• MFGE8 links absorption of dietary fatty acids with catabolism of enterocyte lipid stores through HNF4γ-dependent transcription of CES enzymes.
  Cell reports 2023 Datta R, Gholampour MA, Yang CD, Volk R, Lin S, Podolsky MJ, Arnold T, Rieder F, Zaro BW, Verzi M, Lehner R, Abumrad N, Lizama CO, Atabai K
• DOP32 Crohn’s disease stricture matrisome analysis reveals the anti-fibrotic activity of milk-fat globule-epidermal growth factor 8 (MFGE8).
  Journal of Crohn's and Colitis 2023 S Lin, J Wang, P Mukherjee, R Mao, G West, D Czarnecki, S Zhao, M Elias, Q T Nguyen, J Chandra, T H N Le, M H Chen, D Dejanovic, S Holubar, M Olman, B Southern, S Hu, I O Gordon, K Atabai, C Fiocchi, …
• Autoregulation of insulin receptor signaling through MFGE8 and the αvβ5 integrin.
  Proceedings of the National Academy of Sciences of the United States of America 2021 Datta R, Lizama CO, Soltani AK, Mckleroy W, Podolsky MJ, Yang CD, Huynh TL, Cautivo KM, Wang B, Koliwad SK, Abumrad NA, Atabai K
• You Say You Want a Resolution (of Fibrosis).
  American journal of respiratory cell and molecular biology 2020 Atabai K, Yang CD, Podolsky MJ
• CD81 Controls Beige Fat Progenitor Cell Growth and Energy Balance via FAK Signaling.
  Cell 2020 Oguri Y, Shinoda K, Kim H, Alba DL, Bolus WR, Wang Q, Brown Z, Pradhan RN, Tajima K, Yoneshiro T, Ikeda K, Chen Y, Cheang RT, Tsujino K, Kim CR, Greiner VJ, Datta R, Yang CD, Atabai K, McManus MT, …
• Age-dependent regulation of cell-mediated collagen turnover.
  JCI insight 2020 Podolsky MJ, Yang CD, Valenzuela CL, Datta R, Huang SK, Nishimura SL, Dallas SL, Wolters PJ, Le Saux CJ, Atabai K
• Fat fibrosis: friend or foe?
  JCI insight 2018 Datta R, Podolsky MJ, Atabai K
• Autocrine Mfge8 Signaling Prevents Developmental Exhaustion of the Adult Neural Stem Cell Pool.
  Cell stem cell 2018 Zhou Y, Bond AM, Shade JE, Zhu Y, Davis CO, Wang X, Su Y, Yoon KJ, Phan AT, Chen WJ, Oh JH, Marsh-Armstrong N, Atabai K, Ming GL, Song H
• Deletion of MFGE8 Inhibits Neointima Formation upon Arterial Damage.
  Thrombosis and haemostasis 2018 Viola JR, Lemnitzer P, Paulin N, Drechsler M, Nazari-Jahantigh M, Maas S, De Jong RJ, Winter J, Schober A, Weber C, Atabai K, Soehnlein O
• Cell division cycle 7 kinase is a negative regulator of cell-mediated collagen degradation.
  American journal of physiology. Lung cellular and molecular physiology 2018 Podolsky MJ, Gupta D, Ha A, Ta R, Khalifeh-Soltani A, McKleroy W, Datta R, Sheppard D, Atabai K
• The Mfge8-α8β1-PTEN pathway regulates airway smooth muscle contraction in allergic inflammation.
  FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2018 Khalifeh-Soltani A, Gupta D, Ha A, Podolsky MJ, Datta R, Atabai K
• Mfge8 Binding of the avß5 Integrin Promotes Insulin Resistance in Mice.
  Diabetes 2018 RITWIK DATTA, AMIN KHALIFEH-SOLTANI, ARNOLD HA, KAMRAN ATABAI
• Extracellular matrix in lung development, homeostasis and disease.
  Matrix biology : journal of the International Society for Matrix Biology 2018 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, …
• Inflammatory bone loss associated with MFG-E8 deficiency is rescued by teriparatide.
  FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2018 Michalski MN, Seydel AL, Siismets EM, Zweifler LE, Koh AJ, Sinder BP, Aguirre JI, Atabai K, Roca H, McCauley LK
• Inhibition of hepatocyte nuclear factor 1b induces hepatic steatosis through DPP4/NOX1-mediated regulation of superoxide.
  Free radical biology & medicine 2017 Long Z, Cao M, Su S, Wu G, Meng F, Wu H, Liu J, Yu W, Atabai K, Wang X
• Cd36 knockout mice are protected against lithogenic diet-induced gallstones.
  Journal of lipid research 2017 Xie Y, Cifarelli V, Pietka T, Newberry EP, Kennedy SM, Khalifeh-Soltani A, Clugston R, Atabai K, Abumrad NA, Davidson NO
• Abstract 210: Milk Fat Globule Epidermal Growth Factor VIII Mediates Vascular Remodeling by Increasing Inflammation and Smooth Muscle Activation.
  Arteriosclerosis Thrombosis and Vascular Biology 2017 Ting-Hein Lee, Shigekazu Nagata, Kamran Atabai, Hou-Yu Chiang
• Mfge8 regulates enterocyte lipid storage by promoting enterocyte triglyceride hydrolase activity.
  JCI insight 2016 Khalifeh-Soltani A, Gupta D, Ha A, Iqbal J, Hussain M, Podolsky MJ, Atabai K
• Loss Of Fatty Acid Synthase Increases The Severity Of Lung Fibrosis By Preventing Collagen Resorption.
  QJM 2016 Kamran Atabai, Michael Podolsky, Donald Mccarthy
• α8β1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism.
  eLife 2016 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
• Prevention of gallbladder hypomotility via FATP2 inhibition protects from lithogenic diet-induced cholelithiasis.
  American journal of physiology. Gastrointestinal and liver physiology 2016 Tharp KM, Khalifeh-Soltani A, Park HM, Yurek DA, Falcon A, Wong L, Feng R, Atabai K, Stahl A
• IQGAP1-dependent scaffold suppresses RhoA and inhibits airway smooth muscle contraction.
  The Journal of clinical investigation 2014 Bhattacharya M, Sundaram A, Kudo M, Farmer J, Ganesan P, Khalifeh-Soltani A, Arjomandi M, Atabai K, Huang X, Sheppard D
• Polarization of prostate cancer-associated macrophages is induced by milk fat globule-EGF factor 8 (MFG-E8)-mediated efferocytosis.
  The Journal of biological chemistry 2014 Soki FN, Koh AJ, Jones JD, Kim YW, Dai J, Keller ET, Pienta KJ, Atabai K, Roca H, McCauley LK
• Mfge8 promotes obesity by mediating the uptake of dietary fats and serum fatty acids.
  Nature medicine 2014 Khalifeh-Soltani A, McKleroy W, Sakuma S, Cheung YY, Tharp K, Qiu Y, Turner SM, Chawla A, Stahl A, Atabai K
• Functional genomic screen identifies novel mediators of collagen uptake.
  Molecular biology of the cell 2014 Lee TH, McKleroy W, Khalifeh-Soltani A, Sakuma S, Lazarev S, Riento K, Nishimura SL, Nichols BJ, Atabai K
• Always cleave up your mess: targeting collagen degradation to treat tissue fibrosis.
  American journal of physiology. Lung cellular and molecular physiology 2013 McKleroy W, Lee TH, Atabai K
• Mfge8 suppresses airway hyperresponsiveness in asthma by regulating smooth muscle contraction.
  Proceedings of the National Academy of Sciences of the United States of America 2012 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
• IL-17A produced by αβ T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction.
  Nature medicine 2012 Kudo M, Melton AC, Chen C, Engler MB, Huang KE, Ren X, Wang Y, Bernstein X, Li JT, Atabai K, Huang X, Sheppard D
• Mfge8 diminishes the severity of tissue fibrosis in mice by binding and targeting collagen for uptake by macrophages.
  The Journal of clinical investigation 2009 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
• Essential role for MFG-E8 as ligand for alphavbeta5 integrin in diurnal retinal phagocytosis.
  Proceedings of the National Academy of Sciences of the United States of America 2007 Nandrot EF, Anand M, Almeida D, Atabai K, Sheppard D, Finnemann SC
• Roles of the innate immune system in mammary gland remodeling during involution.
  Journal of mammary gland biology and neoplasia 2007 Atabai K, Sheppard D, Werb Z
• Mfge8 is critical for mammary gland remodeling during involution.
  Molecular biology of the cell 2005 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
• Keratinocyte growth factor can enhance alveolar epithelial repair by nonmitogenic mechanisms.
  American journal of physiology. Lung cellular and molecular physiology 2002 Atabai K, Ishigaki M, Geiser T, Ueki I, Matthay MA, Ware LB
• Aerosolized beta(2)-adrenergic agonists achieve therapeutic levels in the pulmonary edema fluid of ventilated patients with acute respiratory failure.
  Intensive care medicine 2002 Atabai K, Ware LB, Snider ME, Koch P, Daniel B, Nuckton TJ, Matthay MA
• The pulmonary physician in critical care. 5: Acute lung injury and the acute respiratory distress syndrome: definitions and epidemiology.
  Thorax 2002 Atabai K, Matthay MA
• Human eosinophils induce mucin production in airway epithelial cells via epidermal growth factor receptor activation.
  Journal of immunology (Baltimore, Md. : 1950) 2001 Burgel PR, Lazarus SC, Tam DC, Ueki IF, Atabai K, Birch M, Nadel JA
• Pulmonary edema fluid from patients with acute lung injury augments in vitro alveolar epithelial repair by an IL-1beta-dependent mechanism.
  American journal of respiratory and critical care medicine 2001 Geiser T, Atabai K, Jarreau PH, Ware LB, Pugin J, Matthay MA
• Increased expression of CD23 (Fc(epsilon) receptor II) by peripheral blood monocytes of aids patients.
  AIDS research and human retroviruses 2001 Miller LS, Atabai K, Nowakowski M, Chan A, Bluth MH, Minkoff H, Durkin HG
• Interleukin-1beta augments in vitro alveolar epithelial repair.
  American journal of physiology. Lung cellular and molecular physiology 2000 Geiser T, Jarreau PH, Atabai K, Matthay MA