Co-Chief, Dry Eye Clinic
UCB Associate Professor
Molecular and Cellular Laboratory
Dr. McNamara's research centers on understanding the role of innate immunity in protecting host epithelial cells from environmental injury. Mucosal epithelial cells interface with the environment at all body surfaces, including the eye. Thus, the mucosa is often the first line of defense against environmental injury. Mucosal cells use a general defense strategy and are believed to play a critical role in regulating the more powerful adaptive immune response. Unfortunately, sometimes the immune system goes into overdrive and creates a pathological state. Examples of this include ocular allergy, dry eye disease, bacterial infection and even cancer. In each of these disease entities there is an immunological component that either initiates or enhances the disease state. Dr. McNamara's work focuses on dissecting the molecular events that underlie early immune responses. Her research program involves clinical studies of the human ocular surface, as well as both in vivo and in vitro studies of the immune pathways that promote inflammation in the pathological state. This work will lead to a better understanding of the molecular patterns that contribute to pathology and suggest new strategies for modulating the response in favor of the host.
Pathogenesis of autoimmune-mediated eye disease
One of the most debilitating forms of dry eye, known clinically as keratoconjunctivitis sicca (KCS), results from autoimmune diseases that affect the lacrimal gland and ocular surface. Sjögren's syndrome (SS) is a prime example where infiltration of the lacrimal gland with lymphocytes causes recalcitrant dry eye. To explore the dynamics of dry eye in autoimmune diseases like SS, my laboratory uses a mouse model to mimics the clinical characteristics. We have shown a role for auto antigen-primed, CD4+ T lymphocytes in promoting ocular surface damage in autoimmune dry eye and have been able to extend these findings to human patients with SS. Moreover, we have gone on to identify specific inflammatory proteins and intracellular intermediates that connect T cell infiltration to KCS. Among these intermediates, we found a key role for the inflammatory cytokine, interleukin 1β and tissue macrophages. We are currently pursuing studies that include both pharmacological and genetic alteration of interleukin-1 and macrophage signaling.
Sjögren's International Collaborative Clinical Alliance (SICCA)
My experience in the area of autoimmune ocular surface disease extends into the clinical arena through my work with SICCA. As a SICCA investigator, I collect clinical data and biospecimens for the Sjögren's Syndrome Registry. In the past two years, I have co-authored SICCA publications that describe an ocular scoring system for dry eye disease and a new classification criteria for the diagnosis of SS.
Smoke-Induced Lung Cancer: Role of EGFR, MUC1 and Catenins
Within the past six years, my research program has expanded into the area of cancer research. Specifically, my laboratory is focused on deciphering the stress response of airway mucosal epithelial cells to toxins/carcinogens contained in tobacco smoke. Smoking represents the single most important carcinogenic exposure and is the leading cause of cancer-related mortalities. In order to identify drug targets that can be exploited by pharmaceutical companies to alleviate and/or prevent lung cancer caused by tobacco smoke, my lab uses a novel, 3-dimensional experimental model of stratified bronchial epithelial cells to simulate the in vivo airway. Cells are exposed to smoke using a fast, easy, and reproducible method, which offers the opportunity to perform manipulations at a molecular level. Using this model, we have explored the early steps in smoke-induced lung cancer. We discovered that tobacco smoke disrupts the interactions between mucosal epithelial cells and liberates the cell junction protein, β-catenin. Once released from the cell surface, β-catenin is transported to the nucleus where it turns on pro-tumor genes. These studies suggest that early alterations by smoke induce pre-neoplastic changes of the healthy lung that have the functional capacity to promote tumorigenesis. Moreover, we found that another cell junction protein, p120catenin, is essential for promoting migration of airway epithelial cells in response to cigarette smoke. A deeper understanding of smoke-induced cell migration may provide a platform for screening new drug candidates that suppress tumor progression and cell migration in metastatic disease.
Dry Eye Clinic
Supervising OD interns in the testing, diagnosis, and treatment of patients with ocular surface disease in the Meredith W. Morgan University Eye Center
Rutar T, Youm J, Porco T, Tilton N, Muskat M, McNamara N, Wara D. Ophthalmic manifestations of perinatally acquired HIV in a US cohort of long-term survivors. Br J Ophthalmol. 2015 May; 99(5):650-3. PMID: 25416182
Rose-Nussbaumer J, Lietman TM, Shiboski CH, Shiboski SC, Bunya VY, Akpek EK, Srinivasan M, Mascarenhas J, Massaro-Giordano G, McNamara NA, Whitcher JP, Gaynor BD. Inter-grader Agreement of the Ocular Staining Score in the Sjögren's International Clinical Collaborative Alliance (SICCA) Registry. Am J Ophthalmol. 2015 Dec; 160(6):1150-1153.e3. PMID: 26302236. PMCID: PMC4651820
Stephens DN, McNamara NA. Altered Mucin and Glycoprotein Expression in Dry Eye Disease. Optom Vis Sci. 2015 Sep; 92(9):931-8. PMID: 26267059
Moy A, McNamara NA*, Lin MC*. Effects of Isotretinoin on Meibomian Glands. Optom Vis Sci. 2015 Sep; 92(9):925-30. *Shared senior authorship PMID: 26154692
McNamara NA, Ge S, Lee SM, Enghauser AM, Kuehl L, Chen FY, Gallup M, McKown RL. Reduced levels of lacritin are associated with corneal neuropathy in patients with the ocular component of Sjögren's syndrome. Invest Ophthalmol Vis Sci. 2016 Oct 1; 57(13):5237-5243. PMID: 27711909. PMCID: PMC5063056
Zhang L, Gallup M, Zlock L, Chen YT, Finkbeiner WE, McNamara NA. Cigarette smoke mediates nuclear to cytoplasmic trafficking of transcriptional inhibitor Kaiso through MUC1 and p120-catenin. Am J Pathol. 2016 Oct 17. PMID: 27765636. PMID: PMC5225293
Vaishnav YJ, Rucker SA, Saharia K, McNamara NA. Rapid, automated mosaicking of the human corneal subbasal plexus. Biomed Tech (Berl). 2017 Mar 4. PMID: 28258973
Farmer DT, Finley JK, Chen FY, Tarifeno-Saldivia E, McNamara NA, Knox SM, McManus, MT. miR-205 is a critical regulator of lacrimal gland development. Dev Biol. 2017 Jul 1;427(1):12-20. PMID: 28511845
Belmonte C, Nichols JJ, Cox SM, Brock JA, Begley CG, Bereiter DA, Dartt DA, Galor A, Hamrah P, Ivanusic JJ, Jacobs DS, McNamara NA, Rosenblatt MI, Stapleton F, Wolffsohn JS. TFOS DEWS II pain and sensation report. Ocul Surf. 2017 Jul;15(3):404-437. PMID: 287363339
Chen FY, Lee A, Ge S, Nathan S, Knox SM, McNamara NA. Aire-deficient mice provide a model of corneal and lacrimal gland neuropathy in Sjogren’s syndrome. PLoS One. 2017 Sep 19;12(9):e0184916. eCollection 2017. PMID: 28926640
Chen YF, Zhou D, Metzger T, Gallup M, Jeanne M, Gould DB, Anderson MS, McNamara NA. Spontaneous Development of Autoimmune Uveitis Is CCR2 Dependent. Am J Pathol. 2014 Jun; 184(6):1695-705.
Zhou D, McNamara NA. Macrophages: important players in primary Sjögren's syndrome? Expert Rev Clin Immunol. 2014 Apr; 10(4):513-20.
Robertson DM, Alexander LJ, Bonanno JA, Fleiszig SM, McNamara N. Cornea and ocular surface disease: application of cutting-edge optometric research. Optom Vis Sci. 2014 Apr; 91(4 Suppl 1):S3-S16.
Chen YT, Chen FY, Vijmasi T, Stephens DN, Gallup M, McNamara NA. Pax6 downregulation mediates abnormal lineage commitment of the ocular surface epithelium in aqueous-deficient dry eye disease.
PLoS One. 2013; 8(10):e77286.
Vijmasi T, Chen FY, Chen YT, Gallup M, McNamara N. Topical administration of interleukin-1 receptor antagonist as a therapy for aqueous-deficient dry eye in autoimmune disease. Mol Vis. 2013;
Zhang L, Gallup M, Zlock L, Basbaum C, Finkbeiner WE, McNamara NA: Cigarette Smoke Disrupts the Integrity of Airway Adherens Junctions through the Aberrant Interaction of P120-catenin with the
Cytoplasmic Tail of MUC1. J Pathol, 229:74-86, 2013.
Zhang L, Gallup M, Zlock L, Finkbeiner WE, McNamara NA: Rac1 and Cdc42 differentially modulate cigarette smoke-induced airway cell migration through p120-catenin dependent and independent pathways. Am J Pathol, 182:1986-1995, 2013.
Chen YT, Chen F, Vijmasi T, Gallup M, McNamara NA: Pax6 downregulation mediates abnormal lineage commitment of the ocular surface epithelium in aqueous-deficient dry eye disease. PLos One
2013, in press.Vijmasi T, Chen F, Chen YT, Gallup M, McNamara NA: Topical administration of IL-1 receptor antagonist as a therapy for aqueous-deficient dry eye in autoimmune disease. Mol Vis 2013, in press.
Zhou D, Chen YT, Chen F, Gallup M, Vijmasi T, Bahrami AF, Noble L, Rooijen N, McNamara NA: Critical involvement of macrophage infiltration in the development of Sjögren’s syndrome-associated dry eye. Am J Pathol 181:753-60, 2012.
Chen YT, Lazarev S, Bahrami AF, Noble LB, Zhou D, Yadav M, McNamara NA: Interleukin-1 receptor signaling mediates the functional interplay between autoreactive CD4+ T cells and ocular resident cells during keratinizing squamous metaplasia in Sjögren’s syndrome. Lab Invest 92:556-70, 2012.
Zhang L, Gallup M, Zlock L, Basbaum C, Finkbeiner WE, McNamara NA: Cigarette Smoke Disrupts the Integrity of Airway Adherens Junctions through the Aberrant Interaction of P120-catenin with the Cytoplasmic Tail of MUC1. J Pathol Jul 26, 2012 [Epub ahead of print].
Shiboski SC, Shiboski CH, Criswell L, Baer A, Challacombe S, Lanfranchi H, Schiødt M, Umehara H, Vivino F, Zhao Y, Dong Y, Greenspan D, Heidenreich AM, Helin P, Kirkham B, Kitagawa K, Larkin
G, Li M, Lietman T, Lindegaard J, McNamara NA, Sack K, Shirlaw P, Sugai S, Vollenweider C, Whitcher J, Wu A, Zhang S, Zhang W, Greenspan J, Daniels T: American College of Rheumatology classification criteria for Sjögren’s Syndrome: A data-driven expert consensus approach in the Sjögren’s International Collaborative Clinical Alliance Cohort. Arthritis Care Res 64:475-87, 2012.
Daniels TE, Cox D, Shiboski CH, Schiodt M, Wu A, Lanfranchi H, Umehara H, Zhao Y, Challacombe S, Lam MY, De Souza Y, Schiodt J, Holm H, Bisio PA, Gandolfo MS, Sawaki T, Li M, Zhang W, Varghese-Jacob B, Ibsen P, Keszler A, Kurose N, Nojima T, Odell E, Criswell LA, Jordan R, Greenspan JS; Sjögren's International Collaborative Clinical Alliance Research Groups. Associations between salivary gland histopathologic diagnoses and phenotypic features of Sjogren’s syndrome among 1,726 registry participants. Arthritis Rheum 63:2021-30, 2011.
Chan MF, Sack RA, Quigley D, Sathe S, Vijmasi T, Holsclaw D, Strauss EC, McNamara NA: Protein array analysis of immune and angiogenic modulators in ocular cicatricial pemphigoid. Opt Vis Sci 88:1005-9, 2011.
Chen YT, Nikulina K, Lazarev S, Gallup M, McNamara NA: Interleukin-1 as a phenotypic immuno-modulator in keratinizing squamous metaplasia of the ocular surface in Sjögren’s syndrome. Am J Pathol 177:1333-43, 2010. PMID: 20696775.
Chen YT, Gallup M, Nikulina K, Zlock L, Finkbeiner W, McNamara NA: Cigarette smoke causes EGFR-mediated depolarization of apical MUC1-mucin and junctional b-catenin in the human airway epithelium. Am J Pathol 177:1255-64, 2010. PMID: 20651243.
Whitcher JP, Shiboski CH, Shiboski SC, Heidenreich AM, Kitagawa K, Zhang S, Hamann S, Larkin G, McNamara NA, Greenspan J, Daniels TE: A simplified quantitative method of assessing keratoconjunctivitis sicca from the Sjogren’s Syndrome International Registry. Am J Ophthalmol 149:405-15, 2010.
Li S, Gallup N, Chen Y-T, McNamara NA: Molecular mechanisms of proinflammatory cytokine-mediated squamous metaplasia in human corneal epithelial cells. Invest Ophthalmol Vis Sci 51:2466-75, 2010.
Liu H, Begley CG, Chen M, Bradley A, Bonanno JA, McNamara N, Nelson JD, Simpson T: A link between tear instability and hyperosmolarity in dry eye. Invest Ophthalmol Vis Sci 50:3671-9, 2009.
Chen YT, Li S, Nikulina K, Porco T, McNamara NA: Immune profile of squamous metaplasia development in autoimmune regulator-deficient dry eye. Mol Vis 15:563-576, 2009.
Sack R, Sathe S, Beaton AR, McNamara N, Fleiszig S, Ni M. Protein array characterization of bioactive proteins secreted by immortalized human corneal epithelium in response to pseudomonas constituents. Curr Eye Res: 34:92-8, 2009.
Li S, Nikulina K, DeVoss J, Wu A, Strauss EC, Anderson MS, McNamara NA: Small protein rich-protein 1B (SPRR1B) is a biomarker for squamous metaplasia in dry eye disease. Invest Ophthalmol Vis
Sci 49:34-41, 2008.
Li S, Sack R, Vijmasi T, Sathe S, Beaton A, Quigley D, Gallup M, McNamara NA: Antibody protein array analysis of the tear film cytokines. Optom Vis Sci 85:653-60, 2008.
Sack RA, Conradi L, Beaton A, Sathe S, McNamara N, Leonardi A: Antibody array characterization of inflammatory mediators in the allergic and normal tears in the open and closed eye environments. Exp Eye Res, 85:528-38, 2007.
Maltseva I, Fleiszig SM, Evans DJ, Kerr S, Sidhu SS, McNamara NA, Basbaum CB: Exposure of human corneal epithelial cells to contact lenses in vitro suppresses the upregulation of human beta-defensin-2 in response to antigens of Pseudomonas aeruginosa. Exp Eye Res, 85:42-53, 2007.
McNamara N, Gallup M, Sucher A, Maltseva I, McKemy D, Basbaum C: AsialoGM1 and TLR5 cooperate in flagellin-induced nucleotide signaling to activate Erk1/2. Am J Respir Cell Mol Biol, 34:653-660, 2006.
Dasari V, Gallup M, Lemjabbar H, Maltseva I, McNamara N: EMT in lung cancer: Is tobacco the "smoking gun"? Am J Respir Cell Mol Biol, 35:3-9, 2006.
McNamara NA, Andika R, Kwong M, Sack RA, Fleiszig SM: Interaction of Pseudomonas aeruginosa with human tear fluid components. Curr Eye Res 7:517-525, 2005.
McNamara N, Gallup M, Khong A, Maltseva I, Fahy J, Dolganov G, Basbaum C: Adenosine upregulation of the mucin gene, MUC2, in asthma. FASEB J 18:1770-2, 2004.
McNamara N: Innate Defense of the Ocular Surface. Eye Contact Lens 29: S10-13, 2003.
McNamara N, Basbaum C: Signaling networks controlling mucin production in response to gram-positive and gram-negative bacteria. Glycoconj J 18: 715-722, 2001.
McNamara N, Khong A, McKemy D, Caterina M, Boyer J, Julius D, Basbaum C: ATP transduces signals from ASGM1, a glycolipid that functions as a bacterial receptor. PNAS 98:9086-9091, 2001.
Belcher CE, Drenkow J, Kehoe B, Gingeras TR, McNamara NA, Lemjabbar H, Basbaum C, and Relman DA: The transcriptional responses of respiratory epithelial cells to Bordetella pertussis reveal
host defensive and pathogen counter defensive strategies. PNAS 97:13847-13852, 2000.
McNamara N, Sack R, Fleiszig SMJ: Mucin-Bacterial Binding Assays. Chapter 35. T. Corfield, ed. Glycoprotein Methods and Protocols, Methods in Molecular Biology. Humana Press, Totowa, NJ, 125:429-437, 1999.