Michael Whitfield, PhD
Institution: Department of Genetics, Dartmouth Medical School
Academic Rank: Associate Professor
Medical School: University of North Carolina/Ph.D./1999
Mailing address: HB7400, Department of Genetics, Hanover, NH 03755
Summary of academic interest: Clarifying the molecular heterogeneity in scleroderma using high throughput gene expression profiling to define diagnostic biomarkers and deregulated pathways.
The goal of my research is to capture the heterogeneity in scleroderma at the molecular level with gene expression profiling and NextGen sequencing. We have demonstrated systematic differences in the gene expression of scleroderma skin (Whitfield et al. PNAS 2003) and identified gene expression based subsets in the skin of scleroderma patients (Milano et al. PLoS ONE 2008). The labs goal is to map the molecular pathways underlying each subset and developing diagnostic test to stratify patients based on their different molecular pathways. We recently demonstrated that deregulation of the TGFbeta pathway underlies a subsets of patients (Sargent et al. J. Invest. Derm. 2010), while IL13/IL4 deregulation underlie the inflammatory subset of patients (Greenblatt et al, 2011). We have mapped each subset to appropriate mouse models and defined novel pathways contributing to disease pathogenesis.
Recent publications relevant to the CORT:
M.L. Whitfield, D. Finlay, J.I. Murray, O. Troyanskaya, J.A. Chi, A. Pergamenschikoy, T.H. McCalmont, P.O. Brown, D. Botstein, and M.K. Connolly, (2003) Systemic and cell-type specific gene expression patterns in scleroderma skin, (2003) Proc Natl Acad Sci U S A. Oct 14;100(21):12319-24.
A. Milano, S.A. Pendergrass, J.L. Sargent, L.K. George, M.K. Connolly and M.L. Whitfield. Molecular subsets in the gene expression patterns of scleroderma skin, (2008) PLoS ONE, Jul 16;3(7):e2696.
J.L. Sargent, A. Milano, M.K. Connolly, and M.L. Whitfield. Scleroderma gene expression and pathway signatures (2008), Current Rheumatology Reports. Jul;10(3):205-11 (Review)
J. Varga and M.L. Whitfield. Transforming growth factor-ß in systemic sclerosis (scleroderma), (2009) Frontiers in Bioscience, Front Biosci (Schol Ed). 2009 Jun 1;1:226-35.
L. Chung, D.F. Fiorentino, M.J. Benbarak, A.S. Adler, M.M. Mariano, R.T. Paniagua, A. Milano, M.K. Connolly, B.D. Ratiner, R.L. Wiskocil, M.L. Whitfield, H.Y. Chang, W.H. Robinson, Molecular Framework for Response to Imatinib Mesylate in Systemic Sclerosis, (2009) Arthritis and Rheumatism, Jan 29;60(2):584-591.
J.L. Sargent, A. Milano, J. Varga, M.K. Connolly, H.Y. Chang, M.L. Whitfield. A TGFbeta-activated gene expression signature is associated with more severe skin disease and internal organ involvement in diffuse cutaneous scleroderma. (2010) J. Invest. Derm., 2010 Mar;130(3):694-705. Epub 2009 Oct 8.
R. Lemaire, J. Bayle, M. Dimarzio, S.A. Pendergrass, A. Milano, M.L. Whitfield, R. Lafyatis. Antagonistic effect of CCN3 on TGF-beta and WNT-mediated fibrillogenesis in systemic sclerosis and marfan syndrome, (2010) J. Invest. Derm., 2010 Jun;130(6):1514-23. Epub 2010 Feb 25.
S.A. Pendergrass, E. Hayes, G. Farina, R. Lemaire, H.W. Farber, M.L. Whitfield, R.A. Lafyatis. Limited systemic sclerosis patients with pulmonary arterial hypertension show biomarkers of inflammation and vascular injury. (2010) PLoS ONE 5(8): e12106.doi:10.1371/journal.pone.0012106
PPARγ downregulation by TGFß in fibroblast and impaired expression and function in systemic sclerosis: a novel mechanism for progressive fibrogenesis. Wei J, Ghosh AK, Sargent JL, Komura K, Wu M, Huang QQ, Jain M, Whitfield ML, Feghali-Bostwick C, Varga J. PLoS One. 2010 Nov 2;5(11):e13778.
Katsumoto TR, Whitfield ML, Connolly MK. The Pathogenesis of Systemic Sclerosis. (2011) Annu Rev Pathol. 2011 Jan 15
Christmann RB, Hayes E, Pendergrass S, Padilla C, Farina G, Affandi AJ, Whitfield ML, Farber HW, Lafyatis R. Interferon and alternative activation of monocyte/macrophages in systemic sclerosis-associated pulmonary arterial hypertension. (2011) Arthritis Rheum. 2011 Jun;63(6):1718-28. doi: 10.1002/art.30318.
Hung T, Wang Y, Lin MF, Koegel AK, Kotake Y, Grant GD, Horlings HM, Shah N, Umbricht C, Wang P, Wang Y, Kong B, Langerød A, Børresen-Dale AL, Kim SK, van de Vijver M, Sukumar S, Whitfield ML, Kellis M, Xiong Y, Wong DJ, Chang HY. Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. (2011) Nat Genet. 2011 Jun 5. [Epub ahead of print]
Sargent JL, Whitfield ML. Capturing the heterogeneity in systemic sclerosis with genome-wide expression profiling. (2011) Expert Rev Clin Immunol. 2011 Jul;7(4):463-73.
Allen JA, Peterson A, Sufit R, Hinchcliff ME, Matthew Mahoney J, Wood TA, Miller FW, Whitfield ML, Varga J. Post-epidemic eosinophilia myalgia syndrome associated with L-tryptophan. (2011) Arthritis Rheum. 2011 Jun 23. doi: 10.1002/art.30514.