Programs & Services
Our laboratory is focused on non-genetic transmission of predisposition to allergy and asthma between generations. This transmission may be a consequence of the parental disease and/or parental environmental exposures. The basic goals of our laboratory are to elucidate the cellular/molecular nature of the parental information, the transmission routes (gametes? intrauterine environment/placenta? breast milk?), and the cellular/molecular receivers of the parental information in offspring. In regard to “receiver” identification, the laboratory initial focus is on cells of the immune system. The translational goals are to identify early life biomarkers of predisposition to allergic diseases and provide targets for development of disease prevention regimens. To accomplish the goals, the laboratory uses mouse models, human cell systems and a variety of immunological, signaling and epigenetic approaches.
Our current mouse model connects asthma predisposition in offspring with maternal exposure to diesel exhaust. In this model, repeated exposure of female mice to diesel exhaust particles (DEP) before or during pregnancy renders their offspring hypersensitive to postnatal allergens. These offspring develop asthma when subjected to suboptimal allergen sensitization and challenge. In contrast, pups born to unexposed mothers do not develop asthma upon suboptimal allergen exposure. Asthma predisposition in this model is associated with abnormal activation of natural killer (NK) cells. Depletion of these cells using specific antibodies prevents asthma. Our immediate goal is to extend these studies through the use of genetic models of NK cell deficiency and adoptive transfer experiments. These approaches will allow us to determine the requirement and sufficiency of fetal NK cell priming and the duration of this priming effect in the postnatal life. We are also conducting experiments aimed to characterize the primed NK cell phenotype and identify the epigenetic and immunological causes of this priming. In addition to studies on NK cells, we plan to test the involvement of conventional pro-asthma cells such as mast cells, eosinophils, T lymphocytes and innate lymphoid type 2 cells. Our further goals are to define maternal factors that contribute to transmission of asthma predisposition to offspring in this model. We are considering placental and breast milk-mediated transmission of environmental toxins, maternal cells and molecules (e.g. cytokines, metabolites). We are also interested in transgenerational epigenetic inheritance through gametes. Furthermore, we plan to develop additional models that will examine the transgenerational effects of other environmental exposures and allergic diseases themselves.
In addition to mouse work, we are conducting experiments using a human cell system. We analyze cord blood samples obtained from neonates born to mothers with asthma. We plan to follow these children for development of asthma. We study cord blood NK cells and other immune cells with a hope to identify an early-life immunological footprint of asthma predisposition.
||Medical University of Lodz, Poland, Habilitation degree
||Medical University of Lodz, Poland, PhD
||Medical University of Lodz, Poland, MD
||National Jewish Health, Denver, CO, Postdoctoral Fellowship
||University of Texas Medical Branch, Galveston, TX, Postdoctoral Fellowship
Awards & Recognition
2015: National Jewish Health Outstanding Scientific Achievement Award
2014-2015: Biomedical Research Grant, American Lung Association
2012-2013: Faculty Development Investigator Award, Denver Children’s Environmental Health Center (NIEHS PO1 ES-018181 and EPA GAD 834515010)
2012: Invited speaker, Presidential Plenary Session, Annual Meeting of the American Academy of Asthma, Allergy and Immunology
2011-2014: KL2 Research Scholar Award, Colorado Clinical and Translational Sciences (NIH, KL2 TR001080)
2011-2013: Sheldon C. Siegel Investigator Grant Award, Asthma and Allergy Foundation of America
2011: Pilot grant, Basic Science Section of the Department of Medicine at National Jewish Health
2010-2011: Junior Faculty Pilot Award, Colorado Clinical and Translational Sciences Institute (NIH, UL1 TR001082)
2009: Invited speaker, Annual Meeting of the European Academy of Allergy and Clinical Immunology
2005-2006: Interest Section Award, American Academy of Asthma, Allergy and Immunology
2000-2002: James W. McLaughlin Award, University of Texas
1998-1999: Ministry of Health Scholarship, Poland
1996: European Union Tempus Scholarship, Nijmegen University Hospital, Holland
1993-1998: Lodz Medical University Scholarship, Poland
1992-1993: Polish Children Fund Scholarship, Poland
American Academy of Asthma, Allergy, and Immunology
American Association of Immunologists
Collegium Internationale Allergologicum
Gorska MM, Stafford SJ, Cen O, Sur S, and Alam R. Unc119, a Novel Activator of Lck/Fyn, is Essential for T Cell Activation. J. Exp. Med. 2004, 199:369-379. PMID: 14757743
Gorska MM, Stafford S, Liang Q, Goplen N, Dharajiya N, Guo L, Sur S, Gaestel M, Alam R. MK2 controls the level of negative feedback in the NF-κB pathway and is essential for endothelial permeability and airway inflammation. J. Exp. Med. 2007, 204:1637-1652. PMID: 17576778
Gorska MM, Goplen N, Liang Q, Alam R. Uncoordinated 119 preferentially induces Th2 differentiation and promotes the development of asthma. J Immunol., 2010, 184:4488-4496. PMID: 20220094.
Gorska MM, Alam R. A mutation in the human Uncoordinated 119 gene impairs TCR signaling and is associated with CD4 lymphopenia. Blood. 2012, 119:1399-1406. PMID:22184408
Manners S, Alam R, Schwartz DA, Gorska MM. A mouse model links asthma susceptibility to prenatal exposure to diesel exhaust. J Allergy Clin Immunol. 2014, 134:63-72.e7. PMID: 24365139. This article was highlighted in the JACI Editorial (Finkelman FD. Diesel exhaust particle exposure during pregnancy promotes development of asthma and atopy. J Allergy Clin Immunol. 2014, 134:73-4. PMID: 24835501)
2005-Present: Assistant Professor, Department of Medicine, Division of Allergy and Clinical Immunology, University of Colorado Denver
Teaching & Professional Positions
Associate Professor, Department of Medicine, Division of Allergy and Clinical Immunology, National Jewish Health
Conflicts of Interest
National Jewish Health physicians and scientists may collaborate with pharmaceutical or other industries to develop medical and scientific breakthroughs or to provide education on trends in quality medical practice
and outcomes to physicians and health professionals around the country. National Jewish Health maintains a strict conflict of interest policy to ensure that all potential conflicts are clearly visible and that management
plans are put in place in order to further innovation and education while ensuring the protection of our patients and the integrity of our research. National Jewish Health publicly discloses any payment to our physicians
or scientists. View this faculty member’s industry relationships and collaborations.
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