Michael Whitfield, PhD
Institution: Department of Genetics, Dartmouth Medical School
Academic rank: Associate Professor
Graduate 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 Associated with the SScores:
Mahoney JM, Taroni J, Martyanov V, Wood TA, Greene CS, Pioli PA, Hinchcliff ME, Whitfield ML. Systems level analysis of systemic sclerosis shows a network of immune and profibrotic pathways connected with genetic polymorphisms. PLoS Comput Biol. 2015 Jan 8;11(1):e1004005. doi: 10.1371/journal.pcbi.1004005. eCollection 2015 Jan. PubMed PMID: 25569146; PubMed Central PMCID: PMC4288710.
Johnson ME, Mahoney JM, Taroni J, Sargent JL, Marmarelis E, Wu MR, Varga J, Hinchcliff ME, Whitfield ML. Experimentally-derived fibroblast gene signatures identify molecular pathways associated with distinct subsets of systemic sclerosis patients in three independent cohorts. PLoS One. 2015 Jan 21;10(1):e0114017. doi: 10.1371/journal.pone.0114017. eCollection 2015. PubMed PMID: 25607805.
Marangoni RG, Korman B, Wei J, Wood TA, Graham L, Whitfield ML, Scherer PE, Tourtellotte WG, Varga J. Myofibroblasts in cutaneous fibrosis originate from adiponectin-positive intradermal progenitors. Arthritis Rheumatol. 2014 Dec 10. doi: 10.1002/art.38990. [Epub ahead of print] PubMed PMID: 25504959.
Iwamoto N, Vettori S, Maurer B, Brock M, Pachera E, Jüngel A, Calcagni M, Gay RE, Whitfield ML, Distler JH, Gay S, Distler O. Downregulation of miR-193b in systemic sclerosis regulates the proliferative vasculopathy by urokinase-type plasminogen activator expression. Ann Rheum Dis. 2014 Nov 10. pii: annrheumdis-2014-205326. doi: 10.1136/annrheumdis-2014-205326. [Epub ahead of print] PubMed PMID: 25384965.
Arron ST, Dimon MT, Li Z, Johnson ME, A Wood T, Feeney L, G Angeles J, Lafyatis R, Whitfield ML. High Rhodotorula sequences in skin transcriptome of patients with diffuse systemic sclerosis. J Invest Dermatol. 2014 Aug;134(8):2138-45. doi: 10.1038/jid.2014.127. Epub 2014 Mar 7. PubMed PMID: 24608988; PubMed Central PMCID: PMC4102619.