Kathryn J. Moore

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Kathryn Moore

Jean and David Blechman Professor of Cardiology, Department of Medicine
Professor, Department of Cell Biology


Contact Info

Address
522 First Avenue
New York, NY 10016

212/263-9259
Kathryn.Moore@nyumc.org

Research Summary

The overall interest of the Moore Laboratory is to understand (1) the role of the innate immune system in sterile inflammatory conditions and host defense, and (2) the role of microRNAs in regulating lipoprotein metabolism and atherosclerosis. The innate immune system senses the presence of invading microorganisms and modified endogenous ligands by recognizing conserved molecular structures that are normally absent in the healthy host. Myeloid cells express classes of pattern recognition receptors, such as the scavenger receptors (SRs) and toll-like receptors (TLRs), that bind conserved a??non-selfa?? patterns to mediate this important function. Although often thought of as a broad, primitive defense mechanism, it is becoming increasingly clear that pattern recognition receptors can cooperate to precisely regulate signaling pathways essential for the proper initiation of innate and acquired immunity. However, the inappropriate activation of these receptors has also been linked to inflammatory syndromes, including atherosclerosis and Alzheimer's disease. MicroRNAs (miRNAs) represent an elegant mechanism of posttranscriptional control of gene expression that serves to fine-tune biological pathways. These tiny noncoding RNAs (20a??22 nucleotide) bind to the 3' untranslated region of mRNAs, thereby repressing gene expression. Recent advances in the understanding of lipid metabolism have revealed that miRNAs, particularly miR-33, play major roles in regulating cholesterol and fatty acid homeostasis. Work from our group identified miR-33, an intronic miRNA located with the sterol response element-binding protein (SREBP)-2 gene, as an important regulator of cellular cholesterol efflux, fatty acid I? oxidation, and high-density lipoprotein metabolism. Using inhibitors of miR-33, we showed in mice and non-human primates that antagonism of this microRNA increases plasma HDL and reduces VLDL triglycerides. These findings have highlighted the important role that miRNAs play in lipoprotein metabolism and opened new avenues for the treatment of dyslipidemias.

Research Keywords

cardiovascular biology

Immune cell screening of a nanoparticle library improves atherosclerosis therapy
Tang, Jun; Baxter, Samantha; Menon, Arjun; Alaarg, Amr; Sanchez-Gaytan, Brenda L; Fay, Francois; Zhao, Yiming; Ouimet, Mireille; Braza, Mounia S; Longo, Valerie A; Abdel-Atti, Dalya; Duivenvoorden, Raphael; Calcagno, Claudia; Storm, Gert; Tsimikas, Sotirios; Moore, Kathryn J; Swirski, Filip K; Nahrendorf, Matthias; Fisher, Edward A; Perez-Medina, Carlos; Fayad, Zahi A; Reiner, Thomas; Mulder, Willem J M. Immune cell screening of a nanoparticle library improves atherosclerosis therapy. Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2016 Nov 01;113(44):E6731-E6740 (2288872)

Netrin-1 and its receptor Unc5b are novel targets for the treatment of inflammatory arthritis
Mediero, Aranzazu; Wilder, Tuere; Ramkhelawon, Bhama; Moore, Kathryn J; Cronstein, Bruce N. Netrin-1 and its receptor Unc5b are novel targets for the treatment of inflammatory arthritis. FASEB journal. 2016 Nov;30(11):3835-3844 (2213582)

Modulation of ambient temperature promotes inflammation and initiates atherosclerosis in wild type C57BL/6 mice
Giles, Daniel A; Ramkhelawon, Bhama; Donelan, Elizabeth M; Stankiewicz, Traci E; Hutchison, Susan B; Mukherjee, Rajib; Cappelletti, Monica; Karns, Rebekah; Karp, Christopher L; Moore, Kathryn J; Divanovic, Senad. Modulation of ambient temperature promotes inflammation and initiates atherosclerosis in wild type C57BL/6 mice. Molecular metabolism. 2016 Nov;5:1121-1130 (2303622)

Netrin-1 is highly expressed and required in inflammatory infiltrates in wear particle-induced osteolysis
Mediero, Aranzazu; Ramkhelawon, Bhama; Wilder, Tuere; Purdue, P Edward; Goldring, Steven R; Dewan, M Zahidunnabi; Loomis, Cynthia; Moore, Kathryn J; Cronstein, Bruce N. Netrin-1 is highly expressed and required in inflammatory infiltrates in wear particle-induced osteolysis. Annals of the rheumatic diseases. 2016 Sep;75(9):1706-1713 (1794812)

Monocyte Adhesion and Plaque Recruitment During Atherosclerosis Development Is Regulated by the Adapter Protein Chat-H/SHEP1
Herbin, Olivier; Regelmann, Adam G; Ramkelawon, Bhama; Weinstein, Erica G; Moore, Kathryn J; Alexandropoulos, Konstantina. Monocyte Adhesion and Plaque Recruitment During Atherosclerosis Development Is Regulated by the Adapter Protein Chat-H/SHEP1. Arteriosclerosis, thrombosis, & vascular biology. 2016 Sep;36(9):1791-1801 (2180242)