Nancy McNamara, OD, PhD

head shot of nancy mcnamar

Title
Professor and Associate Dean for Academic Affairs

Department
School of Optometry

Research Area
Clinical Science; Molecular & Cell Biology

Address
524 Minor Addition
Berkeley, CA 94720-2020

Email
nmcnamara@berkeley.edu

Website
https://eyecare.berkeley.edu/what-we-do-2/speciality-clinics/sjogren/

Affiliations

Professor, UC Berkeley School of Optometry
Associate Dean for Academic Affairs
Chief, UC Berkeley Sjogren’s Clinic
Co-Chief, UC Berkeley Dry Eye Clinic

If you are interested in learning more about the Sjogren’s specialty clinic at UC Berkeley, please click here.

Research Areas

Structure and Function of the Tear Film and Ocular Surface Mucosal Epithelium
The McNamara lab’s earliest research in ocular biology was focused on the interrelationships of mucosal epithelial cells with the innate and adaptive immune systems. This work began during graduate school at the University of California, Berkeley, where Dr. McNamara conducted laboratory studies of tear film physiology and corneal epithelial structure and function in human subjects. Her research consisted of developing a convenient, quantitative fluorophotometric method to assess the barrier function of the ocular surface epithelium, followed by a fellowship at the Mayo Clinic, Rochester, MN, where she examined the effects of diabetic hyperglycemia on corneal physiology by pharmacologically inducing euglycemic and hyperglycemic conditions in diabetic patients.

Innate Defense of Mucosal Surfaces
During Dr. McNamara’s postdoctoral training at the University of California, San Francisco, she explored the role of mucosal immunity in protecting host epithelial cells from environmental insults, such as bacterial infection and chronic inflammation. Specifically, she dissected mechanisms underlying the upregulation of anti-microbial peptides (e.g., defensins) and mucins in response to Pseudomonas aeruginosa.

Key Effector Mechanisms Linking Chronic Inflammation to Dry Eye Pathogenesis
For over a decade, Dr. McNamara’s lab has explored the pathogenesis of dry eye disease with the goal of translating mechanism-based laboratory findings of dry eye immunopathology to the discovery of novel therapeutics. One of the most debilitating forms of dry eye results from autoimmune-mediated destruction of the lacrimal gland, such as that which occurs in Sjögren’s. The McNamara lab has characterized the dry eye phenotype of mice deficient in the autoimmune regulator (Aire) gene that portray key aspects of Sjogren’s immunopathology, including lymphocytic infiltration and destruction of the lacrimal gland, severe aqueous tear deficiency, loss of mucin secreting goblet cells, aberrant activation of epithelial progenitor cells, pathological keratinization of the ocular surface, and the profound loss of corneal nerves. They have shown an essential role for autoantigen-primed, CD4+ T cells in provoking ocular surface disease and have identified specific cytokine and intracellular intermediates that connect CD4+ T cell infiltration to ocular surface disease.

Deepening our Understanding of Sjogren’s-associated Neuropathy
As the McNamara lab continues to explore the molecular mechanisms that drive Sjogren’s-associated dry eye disease, they have established an important collaboration with the Knox lab at UCSF to deepened their understanding of the early stages of autoimmune dry eye development using RNA sequencing. RNAseq has allowed the labs to reveal important signaling pathways that provide valuable diagnostic markers. They have also expanded their basic science investigations to include the lacrimal gland by demonstrating significant neuropathy that closely mimics the peripheral neuropathies occurring in Sjogren’s patients. The McNamara lab established important collaborations with the McManus lab at UCSF to identify miR-205 as a critical regulator of lacrimal gland development and in 2017, Dr. McNamara served as a member of the Tear Film and Ocular Surface Society, Dry Eye Workshop (DEWS II), Pain and Sensation subcommittee to assist to develop a better understanding of the neuropathic changes that contribute to dry eye development and progression.

New Diagnostic Criteria and Novel Therapeutic Approaches for Sjogren’s-associated Dry Eye
Dr. McNamara’s expertise in the area of dry eye disease extends into the clinical arena. Between 2007-2012, she severed as a clinical investigator for the Sjögren’s International Collaborative Clinical Alliance (SICCA). In the laboratory, she explored the mechanistic link between chronic inflammation and corneal neuropathy to identify novel approaches to treat dry eye. She discovered that the naturally occurring tear glycoprotein, lacritin, has impressive neurotrophic properties in the Aire-deficient mouse that complement its well-established role as a prosecretory mitogen with tear-inducing properties. Accordingly, she demonstrated significant improvements in tear secretion, ocular surface integrity, and sensory innervation of the cornea in Aire-deficient mice following the topical application of lacritin. In collaboration with Robert McKown’s lab at James Madison University, they demonstated that 95% of dry eye patients are selectively deficient in lacritin, thus, its topical use as a natural replacement therapy for dry eye presents a tremendous opportunity to fill a large void in the clinical management of Sjogren’s patients. Lacripep (the bioactive peptide of lacritin) received FDA approval in 2016 and the first in-human, double-masked, multi-centered, randomized clinical trial was completed in the Fall of 2019, with UC Berkeley serving as one of the investigation sites. Initial analysis demonstrates significant improvement in inferior corneal staining and reduced symptoms of burning and stinging in Sjogren’s patients.

Teaching

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

Peer Reviewed Publications 2016-2020

10 selected from 77 publications.

1. 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;57(13):5237-5243. ISSN: 1552-5783

2. Vaishnav YJ, Rucker SA, Saharia K, McNamara NA. Rapid, automated mosaicking of the human corneal subbasal nerve plexus. Biomed Tech. 2017 [Epub ahead of print]. PMID: 28258973

3. 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 Dec;186(12):3146-3159. PMID: 27765636

4. 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

5. 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

6. 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 SjÖgren’s syndrome. PLoS One. 2017 Sep 19;12(9):e0184916. PMID: 28926640

7. Chen FY, Gaylord E, McNamara N, Knox S. Deciphering molecular and phenotypic changes associated with early autoimmune disease in the Aire-deficient mouse model of SjÖgren’s syndrome. Int J Mol Sci. 2018 Nov 17;19(11), 3628. PMID: 30453645

8. Klarlund JK, Callaghan JZ, Stella NA, Kowalski RP, McNamara NA, Shanks RMQ. Use of collagen binding domains to deliver molecules to the cornea. J Ocul Pharm Ther. 2019, Nov;35(9):491-496. PMID: 6839418

9. McNamara NA, Polse KA: Community health centers: A model for integrating eye care services with the practice of primary care medicine. Opt Vis Sci. 2019, Dec;96(12):905- 909. PMID: 31834149

10. Alterations in corneal biomechanics underlie early stages of auto immune mediated Dry Eye disease. J Autoimm. 2020; (114):102500