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Kamran Atabai, M.D.
Assistant Adjunct Professor
University of California San Francisco
UCSF Box 2922
phone: (415) 514-4276
fax: (415) 514-4278
email: kamran.atabai@ucsf.edu
 
 

Kamran Atabai received his M.D. degree from the State University of New York-Downstate in 1998.  He completed clinical training in internal medicine at the University of California San Francisco and Pulmonary/Critical Care Medicine training at Harvard Medical School.  Dr. Atabai also completed a postdoctoral research fellowship in the Lung Biology Center at the University of California San Francisco.  He joined the UCSF faculty in 2006.  Dr. Atabai has been the recipient of a National Research Service Award and American Lung Association Fellowship.  He is currently funded through an NIH/NHLBI Mentored Clinical Scientist Development Award (KO8) and an American Lung Association Biomedical Research Grant.

Research Activities
My primary research focus is studying the events that occur after cells that have undergone apoptosis are recognized by their environment and undergo apoptotic cell clearance.  I am particularly interested in this process as it relates to inflammatory and autoimmune diseases of the lung as well as the remodeling process after lung injury.  I am also interested in how this process regulates the normal remodeling process that takes place during mammary gland involution.  To date I have been studying the molecule Milk Fat Globule Epidermal Growth Factor like 8 (Mfge8).   Mfge8 is a secreted glycoprotein that binds phosphatidylserine (PS) residues on apoptotic cells and the avb3 and avb5 integrins on phagocytes, serving as a bridge between apoptotic cells and phagocytes.  Mfge8 is one of several PS binding ligands but thus far the only one identified with a defined in vivo function in apoptotic cell clearance.  Mfge8 binding to PS residues has been proposed to induce secretion of TGF-beta and interleukin 10 suggesting that Mfge8 may modulate the inflammatory milieu.  Our previous studies of mammary gland involution in mice functionally deficient in Mfge8 have delineated a critical in vivo role for this protein in regulating apoptotic cell clearance, mammary gland remodeling, and inflammation during involution.  Interestingly, we found that mammary gland epithelial cells utilizing Mfge8 were the primary cells responsible for clearance of apoptotic cells during involution, with the contribution of tissue macrophages increasing in the latter stages.
In the injured lung, environmental stresses trigger apoptosis in the resident cells of the parenchyma.  There is abundant circumstantial evidence in humans suggesting an association between an excess of apoptotic cells and more severe acute lung injury and pulmonary fibrosis.  In addition, in the bleomycin model of lung injury, pharmacological inhibition of apoptosis abrogates the fibrotic response, suggesting that the apoptotic cell may be fibrogenic.  I am currently investigating what pathogenic and/or homeostatic role the apoptotic cell plays in both the severity of initial injury and in the recovery from acute lung injury.  I am particularly focused on the role of apoptotic cell clearance in this process and whether dysregulated clearance affects tissue remodeling.  I am examining the response to lung injury of mice deficient in Mfge8 as a functional model since Mfge8 is widely expressed in the murine lung and expression is increased with injury.  Mfge8 can be found in alveolar macrophages, alveolar epithelial cells, and epithelial cells and we have found that alveolar macrophages use Mfge8 for apoptotic cell engulfment in vitro.  Interestingly, Mfge8 deficient mice have abnormal alveolar remodeling after bleomycin injury suggesting a regulatory role for this protein in the response to injury.  I am also interested in determining the in vivo roles of several other molecules such as thrombospondin 1, CD47, avb3 and avb5 integrin, and Del1 with proposed roles in this process using knockout mice. I plan to determine which of these molecules are important in lung injury and mammary gland involution as well as whether activation of each of these pathways leads to inhibition or aggravation of inflammation. 
An interesting corollary of this research area is the role of nonprofessional phagocytes such as alveolar epithelial cells and mammary gland epithelial cells in mediating apoptotic cell clearance.  Nonprofessional phagocytes are the first cells to encounter apoptotic neighbors prior to the appearance of professional phagocytes, e.g. macrophages, derived from the immune system.  Another primary hypothesis I am examining is whether nonprofessional phagocytes behave differently after encountering apoptotic cells as compared with their professional counterparts. One possibility is that the professional phagocyte is primarily programmed to eradicate infection.  While a professional phagocyte is adept at engulfing apoptotic cells it encounters, it may not provide the same homeostatic signals that a resident epithelial cell expresses when encountering an apoptotic neighbor.  Thus the response of nonprofessional phagocytes may be geared towards creating a tissue environment that will ameliorate whatever initial stress triggered apoptosis in its neighbors.  One can imagine that these types of responses might be critical in the recovery phase of tissue remodeling after injury both in the lung and other organ systems. 

Selected Publications
Nandrot EF, Anand M, Almeida D, Atabai K, Sheppard D, Finnemann SC. Essential role for MFG-E8 as ligand for {alpha}v{beta}5 integrin in diurnal retinal phagocytosis.
Proc Natl Acad Sci U S A. 2007 Jul 9.


Atabai, K, Fernandez, R, Huang, X, Ueki, I, Kline, A, Li, Y, Sadatamansoori, S, Smith-Steinhardt, C, Zhu, W, Pytela, R, Werb, Z, and Sheppard, D. Mfge8 is critical for mammary gland remodeling during involution.  Mol Biol Cell, 2005 Dec;16(12):5528-37. Epub 2005 Sep 29.


Atabai, K, Ware, LB, Snider, ME, Koch, P, Daniel, B, Nuckton, T, 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.


Atabai,  K, Ishigaki, M, Geiser, T, Ueki, I, Matthay, MA, and Ware, LB. Keratinocyte Growth Factor Can Enhance Alveolar Epithelial Repair by Nonmitogenic Mechanisms. Am J Physiol Lung Cell Mol Physiol, 2002 July;283(1):L163-9.


Burgel, PR, Lazarus, SC, Cheng, D, Wei, T, Ueki, IF, Atabai, K, Birch, MB, Nadel, JA. Human Eosinophils induce mucin production in airway epithelial cells via epidermal growth factor receptor activation. J Immunology, 2002 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):1384-1388.


Miller, LS, Atabai, K, Nowakowski, M, Chan, A, Bluth, MH, Minkoff, H, Durkin, HG. Increased expression of CD23 (Fc(epsilon) receptor II) of peripheral blood monocytes of aids patients. AIDS Res Hum Retroviruses 2001 Mar 20;17(5):443-452.


Geiser, T, Jarreau, PH, Atabai, K, Matthay, MA. Interleukin-1beta augments in vitro alveolar epithelial repair. Am J Physiol Lung Cell Mol Physiol 2000 Dec;279(6):L1184-L1190.


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