2019 Gina M. Finzi Memorial Student Fellow
New York University School of Medicine
Study Title: The Natural Killer Cell Ligand Polymorphism HLA-C Asn80Lys and Lupus Nephritis
Mentor: Robert Clancy, Ph.D., Professor, New York University School of Medicine
About the Researcher
Carlucci graduated from the University of Pittsburgh with a degree in biology. After college, Carlucci received an Intramural Research Training Award to spend two years at the National Institutes of Health (NIH) researching lupus under the direction of Dr. Mariana Kaplan. He has recently completed his first year of medical school at New York University School of Medicine where he has continued to study lupus under Dr. Jill Buyon and Dr. Robert Clancy.
How will your Lupus Foundation of America Grant help advance your research career?
“The Gina M. Finzi Fellowship has provided me with an important learning opportunity to further understand the clinical aspects of lupus. The project I am working on for the Finzi Fellowship includes a significant amount of clinical work, which will enable me to appreciate how the various manifestations of lupus inform scientific discovery and enhance my medical knowledge in this area. I am fortunate that my project also includes a basic science component, which will give me the opportunity to exercise my skills in experimental design and to improve technically at the bench.”
Summary from Carlucci’s Research Proposal
Lupus is an autoimmune disease with a wide range of clinical presentations. Nearly 60% of lupus patients will suffer a potentially severe complication involving their kidneys known as lupus nephritis however, little is known about why some patients are more likely than others to develop this condition. Determining which patients are at risk of having lupus nephritis represents a challenge for clinicians particularly because early recognition is associated with better outcomes. Therefore, it is of significant importance to identify markers that predict which patients will develop kidney damage. A mutation in a protein called the Human Leukocyte Antigen (HLA) is associated with lupus. HLA normally binds to an immune cell, known as a natural killer (NK) cell, that is responsible for suppressing local inflammation. When HLA binds to the NK cell, it is rendered incapable of controlling inflammation, allowing local inflammatory responses to persist unchecked. The mutation we are studying causes HLA to bind to the NK cell more tightly which enhances its inhibition of NK cell function and therefore, promotes inflammation. We hypothesize that this mutation is more likely to be found in patients who eventually develop kidney dysfunction. This association will be evaluated utilizing a well-characterized cohort of lupus patients. A positive association between this mutation and lupus nephritis would lead to a new genetic marker that could be used to predict which lupus patients are at risk of kidney damage and could help clinicians initiate early treatments. In addition, this pathway could be assessed for its potential to be targeted by a drug in order to treat lupus nephritis.
*indicates co-first authors
- Purmalek MM*, Carlucci PM*, Sakhardande S, Dey AK, Temesgen-Oyelakin Y, Joshi AA, Lerman JB, Fike A, Davis M, Chung J, Playford M, Naqi M, Salahuddin T, Natarajan B, Manna Z, Gupta S, Grayson P, Chen M, Hasni S, Mehta N, Kaplan MJ. (2019) Lipoprotein Subfractions and GlycA associate with coronary plaque burden in systemic lupus erythematosus. Lupus Sci Med. 10.1136/lupus-2019-000332.
- Byrd AS*, Carmona-Rivera C*, O’Neil L, Carlucci PM, Kerns M, Caffery JA, Milner SM, Sacks JM, Aliu O, Cisar C, Robinson W, Reichner JS, Miller LS, Okoye GA, Kaplan MJ. (2019) Neutrophil extracellular traps and autoantibodies play a role in the pathogenesis of hidradenitis suppurativa. Sci Transl Med. 10.1126/scitranslmed.aav5908.
- Carlucci P, Luttrell-Williams E, Bhan R, Trad C, El Bannoudi H, Izmirly P, Belmont H, Buyon J, Berger J. (2019) Association Between Neutrophil to Lymphocyte, Monocyte to Lymphocyte, and Platelet to Lymphocyte Ratios and Lupus Disease Activity and Lupus Nephritis [abstract]. Arthritis Rheumatol; 71 (suppl 10).
- Hasni S, Gupta S, Davis M, Poncio E, Temesgen-Oyelakin Y, Carlucci P, Wang X, Naqi M, Playford M, Goel R, Li X, Biehl A, Ochoa-Navas I, Manna Z, Shi Y, Thomas D, Chen J, Biancotto A, Apps R, Cheung F, Kotliarov Y, Babyak A, Stagliano K, Tsang J, Tsai W, Vian L, Gazaniga N, Giudice V, Brooks S, Mackay M, Gregersen P, Diamond B, Mehta N, Remaley A, O'Shea J, Gadina M, Kaplan M. (2019) A Phase 1b/2a Trial of Tofacitinib, an Oral Janus Kinase Inhibitor, in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol; 71 (suppl 10).
- Carlucci PM*, Purmalek MM*, Dey AK, Temesgen-Oyelakin Y, Sakhardande S, Joshi AA, Lerman JB, Fike A, Davis M, Chung J, Playford M, Naqi M, Mistry P, Gutierrez-Cruz G, Dell’Orso S, Naz F, Salahuddin T, Natarajan B, Manna Z, Tsai W, Gupta S, Grayson P, Teague H, Chen M, Sun H, Hasni S, Mehta N, Kaplan MJ. (2018). Neutrophil subsets and their gene signature associate with vascular inflammation and coronary atherosclerosis in lupus. JCI Insight. 3(8):e99276.
- Hasni S, Gupta S, Davis M, Poncio E, Temesgen-Oyelakin Y, Joyal E, Fike A, Manna Z, Auh S, Shi Y, Chan D, Carlucci P, Biehl A, Dema B, Charles N, Balow J, Waldman M, Siegel RM, Kaplan MJ, Rivera J. (2018). Safety and tolerability of omalizumab, a randomized clinical trial of humanized anti-IgE monoclonal antibody in systemic lupus erythematosus (STOP LUPUS). Arthritis Rheumatol. 10.1002/art.40828.
- Cliff R, Uchtenhagen H, Kaplan MJ, Carmona-Rivera C, Carlucci PM, Mikecz K, Markovics A, Carlin J, Buckner J, James E. (2018). Citrullinated aggrecan epitopes as targets of auto-reactive CD4+ T cells in patients with rheumatoid arthritis. Arthritis Rheumatol. 10.1002/art.40768.
- Mistry P, Carmona-Rivera C, Ombrello AK, Hoffmann P, Seto N, Jones A, Stone DL, Naz F, Carlucci P, Dell’Orso S, Gutierrez-Cruz G, Sun HW, Kastner DL, Aksentijevich I, Kaplan MJ. (2018). Dysregulated neutrophil responses and neutrophil extracellular trap for.mation and degradation in PAPA syndrome. Ann Rheum Dis. 10.1136/annrheumdis-2018-213746.
- Casey K, White W, Seto NL, Playford M, Smith M, Carlucci P, Yu B, Wang L, Illei G, Mehta N, Kaplan MJ. (2018) Alteration of Vascular Inflammatory Markers in SLE By Anifrolumab in the Phase IIb Muse Study [abstract]. Arthritis Rheumatol; 70 (suppl 10).
- Carlucci P, Purmalek M, Sakhardande S, Temesgen-Oyelakin Y, Dey AK, Joshi AA, Lerman JB, Fike A, Davis M, Sun HW, Chung JH, Playford MP, Mistry P, Gutierrez-Cruz G, Dell'Orso S, Naz F, Teague H, Manna ZG, Grayson PC, Naqi M, Chen M, Hasni SA, Mehta NN, Kaplan MJ. (2017) Neutrophil Gene Signature and Low Density Granulocyte Subsets Associate with Coronary Plaque Burden and Vascular Inflammation in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol; 69 (suppl 10).
- Carmona-Rivera C, Carlucci PM, Moore E, Lingampalli N, Uchtenhagen H, James E, Liu Y, Bicker KL, Wahamaa H, Hoffman V, Catrina AI, Thompson P, Buckner JH, Robinson WH, Fox DA, Kaplan MJ (2017). Synovial fibroblast-neutrophil interactions promote pathogenic adaptive immunity in rheumatoid arthritis. Science Immunol. 2(10), eaag3358.
- Zhang N, Carlucci P, Nguyen J, Hayes-Jackson JW, Tonsor S. (2016). Contrasting avoidance – tolerance response from thermally contrasting climates in Arabidopsis thaliana. bioRxiv. 10.1101/044461.
For more information on Lupus Foundation on America’s granted research, please contact Ashley Marion at [email protected]