Research
The long-term goals of my laboratory are to delineate the molecular pathways responsible for lymphocyte dysfunction in autoimmune diseases such as Systemic Lupus Erythematosus and Rheumatoid Arthritis (RA). Our work initially focused on IRF4, a transcription factor that it is absolutely required for the production of IL17 and IL-21, two cytokines that have been implicated in the pathogenesis of multiple autoimmune disorders including SLE and RA. IRF4 also plays a fundamental role in B cell activation and differentiation. During studies aimed at isolating proteins interacting with IRF4, we cloned a novel protein termed Def6. We have found that Def6 exerts an important immunoregulatory role in vivo as demonstrated by the finding that Def6-deficient mice can, in the presence of additional genetic manipulations, develop either lupus or RA. At a molecular level, we have found that autoimmunity in these mice is due to dysregulated IRF function and aberrant regulation of Rho GTPase-ROCK mediated pathways. Notably we have recently shown that disease in these mice is critically dependent on Age-associated B cells (ABCs) and exhibits a sex-bias enabling us to harness this model to investigate the molecular mechanisms that control the well-known sex differences that accompany the development of autoimmunity in humans.
Current projects:
- Role of Age-Associated B cells in autoimmunity
- Role of ROCK kinases in autoimmunity
Bio
Pernis earned her Bachelor’s Degree in Biochemistry from Barnard College in 1981 and her MD degree from Columbia University Medical Center (CUMC) in 1986. She completed a residency in Internal Medicine at CUMC in 1989 followed by a fellowship in Allergy and Immunology at CUMC, which included postdoctoral training under the combined mentorship of Dr. Schindler and Dr. Rothman.
Distinctions:
- Irma T. Hirschl Trust Award, Irma T. Hirschl Trust
- Saydman Award, Columbia University Medical Center
- Silverberg Award, Columbia University Medical Center
Selected Publications:
- Manni M, Gupta S, Ricker E, Chinenov Y, Park SH, Shi M, Pannellini T, Jessberger R, Ivashkiv LB, Pernis AB. Regulation of age-associated B cells by IRF5 in systemic autoimmunity. Nat Immunol. 2018 Apr;19(4):407-419.
- Ricker E, Manni M, Flores-Castro D, Jenkins D, Gupta S, Rivera-Correa J, Meng W, Rosenfeld AM, Pannellini T, Bachu M, Chinenov Y, Sculco PK, Jessberger R, Prak ETL, Pernis AB. Altered function and differentiation of age-associated B cells contribute to the female bias in lupus mice. Nat Commun. 2021 Aug 10;12(1):4813.
- Phalke S, Rivera-Correa J, Jenkins D, Flores Castro D, Giannopoulou E, Pernis AB. Molecular mechanisms controlling age-associated B cells in autoimmunity. Immunol Rev. 2022 May;307(1):79-100.