Kamran Atabai, MD

Associate Prof in Residence
Medicine
+1 415 514-1159

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.

Publications: 

Milk fat globule-epidermal growth factor 8 (MFGE8) prevents intestinal fibrosis.

Gut

Lin S, Wang J, Mukherjee PK, Mao R, West G, Czarnecki D, Zhao S, Nguyen QT, Elias M, Massey WJ, Liu W, Wang Y, Prasad A, Banerjee S, Goren I, Chandra J, Le HT, Dejanovic D, Li J, Chen M, Holubar S, Olman M, Southern B, Hu S, Gordon IO, Atabai K, Fiocchi C, Rieder F

The American Thoracic Society Research Program (ATSRP) - Twenty Years of Driving Discovery in Respiratory Medicine.

American journal of respiratory and critical care medicine

Atabai K, Badr MS, Costello J, Ridge K, Rounds S, Turenne M, White ES, Roman J

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

Nature communications

Podolsky MJ, Kheyfets B, Pandey M, Beigh AH, Yang CD, Lizama CO, Datta R, Lin LL, Wang Z, Wolters PJ, McManus MT, Qi L, Atabai K

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

Tu1246 CROHN'S DISEASE STRICTURE MATRISOME ANALYSIS REVEALS THE ANTI-FIBROTIC ACTIVITY OF MILK-FAT GLOBULE-EPIDERMAL GROWTH FACTOR 8 (MFGE8).

Gastroenterology

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, Brian D. Southern, Shaomin Hu, Ilyssa O. Gordon, Kamran Atabai, Claudio Fiocchi, Florian Rieder

MFGE8 links absorption of dietary fatty acids with catabolism of enterocyte lipid stores through HNF4?-dependent transcription of CES enzymes.

Cell reports

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

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, F Rieder

Autoregulation of insulin receptor signaling through MFGE8 and the αvβ5 integrin.

Proceedings of the National Academy of Sciences of the United States of America

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

Atabai K, Yang CD, Podolsky MJ

CD81 Controls Beige Fat Progenitor Cell Growth and Energy Balance via FAK Signaling.

Cell

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, Koliwad SK, Spiegelman BM, Kajimura S

Age-dependent regulation of cell-mediated collagen turnover.

JCI insight

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

Datta R, Podolsky MJ, Atabai K

Autocrine Mfge8 Signaling Prevents Developmental Exhaustion of the Adult Neural Stem Cell Pool.

Cell stem cell

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

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

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

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

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

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

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

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

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

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

Ting-Hein Lee, Shigekazu Nagata, Kamran Atabai, Hou-Yu Chiang

Mfge8 regulates enterocyte lipid storage by promoting enterocyte triglyceride hydrolase activity.

JCI insight

Khalifeh-Soltani A, Gupta D, Ha A, Iqbal J, Hussain M, Podolsky MJ, Atabai K

α8β1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism.

eLife

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

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

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

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

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

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

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

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

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

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

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

Atabai K, Sheppard D, Werb Z

Mfge8 is critical for mammary gland remodeling during involution.

Molecular biology of the cell

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

Atabai K, Ishigaki M, Geiser T, Ueki I, Matthay MA, Ware LB

Human eosinophils induce mucin production in airway epithelial cells via epidermal growth factor receptor activation.

Journal of immunology (Baltimore, Md. : 1950)

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

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

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

Geiser T, Jarreau PH, Atabai K, Matthay MA

Research Area: 
Adipocyte and Metabolism