Michelle A. Lowes, MD, PhD

Michelle A. Lowes Dr Lowes is an Associate Professor of Clinical Investigation in the Laboratory for Investigative Dermatology. Her broad research area is skin immunology, with a "dendritic cell-centric" focus. The classic function of dendritic cells is to sense "danger", migrate to local lymph nodes and present antigen for T cell activation and adaptive immunity. Dr Lowes has an interest in human skin-derived dendritic cells, particularly from a translational perspective.

Dr Lowes has predominantly studied psoriasis, as an accessible model of inflammation, utilizing biologic therapeutics to study the role of the immune system in this disease. Psoriasis is a common complex inflammatory skin disease, a result of interactions between cells of the skin and the immune system, including keratinocytes, T lymphocytes, and dendritic cells. The skin disease psoriasis is an ideal model to study these dendritic cells due to their accumulation during inflammation, the accessibility of the skin to sample involved areas, and the opportunity to modulate disease activity with systemic treatments. She has developed and refined techniques required to phenotype, localize, isolate, and study dendritic cells and T cells from healthy and diseased human skin. She also applies her skills and knowledge to the study of other chronic inflammatory skin diseases and cutaneous malignancy.

Early on in her studies with Dr James Krueger, Dr Lowes discovered "TIP-DCs", TNF- and iNOS-producing dendritic cells that were abundant in psoriasis skin lesions. These cells are part of the group of "inflammatory dendritic cells", which may be critical for causing psoriasis. These inflammatory dendritic cells are reduced with every treatment for psoriasis examined, including alefacept, efalizumab, etanercept, cyclosporine, and narrow band ultraviolet B (NB-UVB) radiation. Dr Lowes also studies other skin-associated leukocyes such as macrophages and T cells. Future studies in her group will focus on defining the origin of these inflammatory dendritic cells and producing them in vitro. Once in the skin, the local inflammatory environment drives activation and polarization of the dendritic cells, and hence T cells. Being able to prevent this migration and activation presents a novel therapeutic strategy.

Dr Lowes obtained her medical degree from the University of New South Wales, Australia, her PhD from the University of Sydney, Australia, and is a board-certified Dermatologist in Australia. She came to Rockefeller University in 2001, and joined the Clinical Scholars Program. She has been an NIH-funded investigator since 2006, and has also received funding from The Doris Duke Foundation, The Dana Foundation, and the Rockefeller University Clinical and Translational Science Award (CTSA). Dr Lowes is a Fellow of the Australasian College of Dermatologists, an International Fellow of the American Academy of Dermatology, a fellow of the Society of Investigational Dermatology, a member of the Women's Dermatologic Society and the Society for Clinical and Translational Science. Dr Lowes also serves in several advisory roles, including as a member of the Advisory Committee for Clinical and Translational Science (ACCTS) at Rockefeller University (since 2008), a member of the Editorial Board of the Journal of Clinical Immunology (Jan 1, 2009-Dec 31, 2012), as well as a Faculty member for Faculty of 1000 Medicine/F1000 (since 2008) in the section "Psoriasis & other inflammatory diseases".

Publications:

1. Suárez-Fariñas M, Fuentes-Duculan J, Lowes MA, Krueger JG. Resolved psoriasis lesions retain expression of a subset of disease-related genes. J Invest Dermatol, Sep 2010. PMID: 20861854

2. Johnson-Huang LM, Suáez-Fariñas M, Sullivan-Whalen M, Gilleaudeau P, Krueger JG, Lowes MA. Effective narrow-band ultraviolet B radiation therapy suppresses the IL-23/IL-17 axis in normalized psoriasis plaques. J Invest Dermatol July 17, 2010. PMID 20555351

3. Fuentes-Duculan J, Suárez-Fariñas M, Zaba LC, Nograles KE, Pierson KC, Mitsui H, Pensabene CA, Kzhyshkowska J, Krueger JG, Lowes MA. A subpopulation of CD163 positive macrophages is classically activated in psoriasis. J Invest Dermatol July 17 2010. PMID: 20555352

4. Zaba LC, Fuentes-Duculan J, Eungdamrong NJ, Johnson-Huang LM, Nograles KE, White TR, Pierson KC, Lentini T, Suáez-Fariñas M, Lowes MA* and Krueger JG*. Identification of TRAIL and other molecules that distinguish inflammatory DCs from resident DCs in psoriasis. J Allergy Clin Immunol, 2010 125:6 p 1261-1268 e9. PMID: 20471070

5. Suárez-Fariñas M, Lowes, MA, Zaba LC, Krueger JG. Evaluation of the psoriasis transcriptome across different studies by Gene Set Enrichment Analysis (GSEA). PLoS ONE, 2010 5(4) e10247 PMID: 20422035

6. Suárez-Fariñas M, Shah KR, Haider AS, Krueger JG, Lowes MA. Personalized medicine in psoriasis: developing a genomic classifier to predict histological response to Alefacept. BMC Dermatology, 2010, 10:1 PMID: 20152045

7. Zaba LC, Suarez-Farinas M, Fuentes-Duculan J, Nograles KE, Guttman-Yassky E, Cardinale I, Lowes MA*, Krueger JG*. Effective treatment of psoriasis with etanercept is linked to suppression of IL-17 signaling, not "immediate-response" TNF genes. J Allergy Clin Immunol, 2009. Nov;124(5):1022-10.e1-395 PMID: 19895991

8. Bluth MJ, Zaba LC, Moussai D, Suarez-Farinas M, Kaporis H, Fan L, Pierson KC, White,TR, Pitts-Kieffer A, Guttman-Yassky E, Krueger J, Lowes MA, Carucci J. Myeloid dendritic cells from human squamous cell carcinoma are poor stimulators of T cell proliferation. J Invest Dermatol 2009 Oct;129(10):2451-62. Epub 2009 Apr 23. PMID: 19387481

9. Guttman-Yassky E, Lowes MA, Fuentes-Duculan J, Zaba LC, Cardinale I, Nograles KE, Khatcherian A, Novitskaya I, Carucci JA, Bergman R, and Krueger JG. Low expression of the IL-23/Th17 pathway in atopic dermatitis compared to psoriasis. J Immunology, 2008. Nov 15;181(10):7420-7. PMID: 18981165

10. Nograles KE, Zaba LC, Guttman-Yassky E, Fuentes-Duculan J, Suárez-Fariñas M, Cardinale I, Khatcherian A, Gonzalez J, Pierson KC, White TR, Pensabene C, Coats I, Novitskaya I, Lowes MA, Krueger JGTh17 cytokines interleukin (IL-17) and IL-22 modulate distinct inflammatory and keratinocyte response pathways. Br J of Dermatol 2008. 159(5)1092. PMID: 18684158

11. Zaba LC, Fuentes-Duculan J, Eungdamrong, NJ, Abello MV, Novitskaya I, Pierson K, Gonzalez J, Krueger JG, Lowes MA. Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell polarizing myeloid dendritic cells. J Invest Dermatol 2009 Jan;129(1):79 PMID: 18633443

12. Guttman-Yassky E, Vugmeyster Y, Lowes MA, Chamian F, Kikuchi T, Kagen M, Gilleaudeau P, Lee E, Brisdell Hunte, Howell K, Dummer W, Bodary SC, and Krueger JG. Blockade of CD11a by efalizumab in psoriasis patients induces a unique state of T cell hyporesponsiveness. J Invest Dermatol 2008 May;128(5):1182 PMID: 18239614

13. Haider AS, Lowes MA, Suárez-Fariñas M, Zaba LC, Cardinale I, Khatcherian A, Novitskaya I, Wittkowski KM, Krueger JG. Identification of cellular pathways of "type 1"-, Th-17- T cells and Tip-DCs in autoimmune inflammation through pharmacogenomic study of cyclosporine A (CSA) in psoriasis. J Immunol 2008.180(3):1913 PMID: 18209089

14. Lowes MA, Kikuchi T, Fuentes-Duculan J, Cardinale I, Zaba LC, Haider AS, Bowman EP, Krueger JG. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol, 2008 May;128(5):1207 PMID: 18200064

15. Adams S, Lowes MA, O.Neill DW, Schachterle S, Romero P, Bhardwaj N. Lack of functionally active Melan-A26-35 specific T cells in the blood of HLA-A2+ vitiligo patients. J Invest Dermatol 2008 March 13 [Epub ahead of print]. PMID: 18337837

16. Haider AS, Lowes MA, Suárez-Fariñas M, Zaba LC, Cardinale I, Blumenberg M, Krueger, JG. Cellular genomic maps help dissect pathology in human skin disease, J Invest Dermatol 2008 Mar;128(3):606-15. Epub 2007 Oct 11. PMID: 17928892

17. Zaba, LC, Cardinale I, Gilleaudeau P, Sullivan-Whalen M, Suárez-Fariñas M, Fuentes-Duculan J, Novitskaya I, Khatcherian A, Bluth MJ, L Lowes MA, Krueger JG. Amelioration of epidermal hyperplasia TNF inhibition is associated with reduced Th17 responses. J Exp Med 2007. 204(13):3183 PMID: 18039949

18. Zaba LC, Fuentes-Duculan J, Steinman RM, Krueger JG, Lowes MA. Normal human dermis contains distinct populations of CD11c+ and CD1c+ (BDCA-1)+ dendritic cells and CD163+/FXIIIA+ macrophages. J Clin Invest. 2007. 117(9):2517 PMID: 17786242

19. Chamian F, Lin S-L, Lee E, Kikuchi T, Gilleaudeau P, Sullivan-Whalen M, Cardinale I, Khatcherian A, Novitskaya I, Wittkowski KM, Krueger JG, Lowes MA. Alefacept (anti-CD2) causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis. Journal of Translational Medicine 2007. Jun 7;5:27 PMID: 17555598

20. Haider AS, Lowes MA, Gardner H, Bandaru R, Darabi K, Chamian F, Kikuchi T, Gilleaudeau P, Whalen MS, Cardinale I, Novitskaya I, Krueger JG. Novel insight into agonistic mechanism of alefacept in vivo: Differentially expressed genes may serve as biomarkers of response in psoriasis patients J Immunol. 2007. 178(11):7442 PMID: 17513795

21. Kaporis H, Guttman-Yassky E, Lowes MA, Haider AS, Duculan-Fuentes J, Darabi K, Whynot-Ertelt J, Khatcherian A, Cardinale I, Novitskaya I, Krueger JG, Carucci JA. Human basal cell carcinoma is associated with Foxp3+ T cells in a mixed Th1 and Th2 microenvironment. J Invest Dermatol 2007 Oct;127(10):2391-8 PMID: 17508019

22. Guttman-Yassky E, Lowes MA, Fuentes-Duculan J, Whynot J, Novitskaya I, Cardinale I, Haider A, Khatcherian A, Bergman R, Carucci JA, Krueger JG. Major differences in dendritic cells and their inflammatory products distinguish atopic dermatitis from psoriasis. J Allergy Clin Immunol 2007. 119:1210 PMID: 17472813

23. Lowes MA, Chamian F, Abello MV, Leonardi C, Dummer CW, Papp K, and Krueger JG. Eruptive papules during efalizumab (anti-CD11a) therapy of psoriasis vulgaris: a case series. BMC Dermatol 2007. 7:2. PMID: 17324275

24. Wang F, Lee E, Lowes MA, Haider A, Abello MV, Chamian F, Cardinale I, Krueger JG. IL-20 in Psoriasis: Production by CD68+ Myeloid-Derived Cells, Regulation by Cell Adhesion and Cytokines, and Activation of IFN-γ-Inducible Genes. J Invest Dermatol 2006. 126:1590-9. Epub 2006 Apr 27 PMID: 16645593

25. Lowes MA, Turton, JA, Krueger JG, Barnetson RStC. Psoriasis vulgaris flare during efalizumab therapy does not preclude future use: a case series. BMC Dermatol 2005. 5:9. PMID: 16109173

26. Lowes MA, Chamian F, Abello MV, Fuentes-Duculan J, Lin S-L, Nussbaum R, Novitskaya I, Carbonaro H, Cardinale I, Kikuchi T, Gilleaudeau P, Sullivan-Whalen M, Wittkowski KM, Papp K, Garovoy M, Dummer W, Steinman RM, Krueger JG. Increase in TNF-. and iNOS-expressing dendritic cells in psoriasis and reduction with anti-CD11a. PNAS 2005. 102:19057-19062. PMID: 16380428

27. Gottlieb AB, Chamian F, Masud S, Cardinale I, Abello M, Lowes MA, Chen F, Magliocco M, Krueger JG. Tumor Necrosis Factor (TNF) Inhibition Rapidly Down-Regulates Multiple Pro-Inflammatory Pathways in Psoriasis Plaques, J Immunol 2005. 175:2721-2729. PMID: 16081850

28. Chamian F* and Lowes MA*, Lin SL, Lee E. Kikuchi T, Gilleaudeau P, Sullivan-Whalen M, Cardinale I, Khatcherian A, Novitskaya I, Wittkowski KM, Krueger JG. Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris PNAS 2005. 102(6):2075-2080. PMID: 15671179

29. Vugmeyster Y, Kikuchi T, Lowes MA, Chamian F. Kagen M, Gilleaudeau P, Lee E, Howell K, Bodary S, Dummer W, Krueger JG. Efalizumab (anti-CD11a)-induced increase in peripheral blood leukocytes in psoriasis patients is preferentially mediated by altered trafficking of memory CD8+ T cells into lesional skin. Clin Immunol 2004. 113(1):38-46. PMID: 15380528

30. Wong DA, Bishop GA, Lowes MA, Cooke B, Barnetson RS, Halliday GM. Cytokine profiles in spontaneously regressing basal cell carcinomas. Br J Dermatol 2000. 143(1):91-8. PMID: 10886141

31. Lowes, MA, Norris D, and Whitfeld M. Benign melanocytic proliferative nodule within a congenital naevus. Australas J Dermatol 2000. 41:109-111. PMID: 10812706

32. Lowes, MA, Khaira GS, and Holt D. Transient reactive papulotranslucent acrokeratoderma associated with cystic fibrosis. Australas J Dermatol 2000. 41:172-174. PMID: 10954989

33. Lowes MA, Dunckley H, Watson N, Crotty K, Cooke B, Barnetson RS, Halliday GM. Regression of melanoma, but not keratoacanthoma, is associated with increased HLA-B22 and decreased HLA-B27 and HLA-DR1. Melanoma Res 1999. 9(6):539-44. PMID: 106617644. Lowes MA, Dunckley H, Watson N, Crotty K, Cooke B, Barnetson RS, Halliday GM. Regression of melanoma, but not keratoacanthoma, is associated with increased HLA-B22 and decreased HLA-B27 and HLA-DR1. Melanoma Res 1999. 9(6):539-44. PMID: 10661764

34. Lowes MA, Bishop GA, Cooke BE, Barnetson RS, Halliday GM. Keratoacanthomas have an immunosuppressive cytokine environment of increased IL-10 and decreased GM-CSF compared to squamous cell carcinomas. Br J Cancer 1999. 80(10):1501-5. PMID: 10408389

35. Lowes MA, Bishop GA, Crotty K, Barnetson RS, Halliday GM. T helper 1 cytokine mRNA is increased in spontaneously regressing primary melanomas. J Invest Dermatol 1997. 108(6):914-9. PMID: 9182821

36. Bishop, GA, Rokahr KL, Lowes M, McGuinness PH, Napoli J, DeCruz DJ, Wong WY, and McCaughan GW. Quantitative reverse transcriptase-PCR amplification of cytokine mRNA in liver biopsy specimens using a non-competitive method. Immunol Cell Biol 1997. 75:142-147. PMID: 9107566

Reviews:

1. Johnson-Huang LM, McNutt NS, Krueger JG, Lowes MA. Cytokine-Producing Dendritic Cells in the Pathogenesis of Inflammatory Skin Diseases. J Clin Immunol. 2009. Published online 28 Feb. PMID: 19252974

2. Zaba LC, Krueger JG, Lowes MA. Resident and "Inflammatory" dendritic cells in human skin. J Invest Dermatol 2009 Feb;129(2):302. PMID: 18685620

3. Lowes, MA, Bowcock AM, and Krueger JG. Pathogenesis and therapy of psoriasis. Nature 2007. 445:866-873. PMID: 17314973

4. Lowes, MA, Lew W, and Krueger JG. Current concepts in the immuno-pathogenesis of psoriasis. Dermatol Clin 2004. 22:349-369 PMID: 15450332