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William F.C. Rigby, MD

Title(s):
Professor of Medicine
Professor of Microbiology and Immunology

Department(s):
Medicine
Microbiology and Immunology

Education:
Harvard Medical School, MD 1979
Columbia University, BA 1974


After postdoctoral work in Dr. Michael Fanger's laboratory in the Department of Microbiology at Dartmouth Medical School, Dr. Rigby completed subspecialty training in rheumatology and joined the faculty at Dartmouth Medical School in 1987.

Programs:
Immunology Program
Neuroscience Center at Dartmouth
Program in Experimental and Molecular Medicine

Websites:
http://geiselmed.dartmouth.edu/microbio/
http://geiselmed.dartmouth.edu/immuno/
http://geiselmed.dartmouth.edu/COBRE/
http://geiselmed.dartmouth.edu/rigby/

Contact Information:

Dartmouth Hitchcock Medical Center
Borwell Research Bldg. - HB 7510
1 Medical Center Drive
Lebanon NH 03756

Email: William.Rigby@Dartmouth.EDU


Professional Interests:

Dr. Rigby's laboratory integrates his basic scientific and clinical interests. On a translational level, Dr. Rigby is examining the changes that accompany clinical responses in patients with rheumatoid arthritis treated with biologics. His basic scientific efforts examine the mechanism by which CD40 ligand (CD154) and cytokine expression are regulated at post-transcriptional levels. Many cytokines are encoded by mRNA that contain reiterated AUUUA sequences in their 3' UTR. These AU-rich sequences (AURE) have been shown to modulate the translation as well as rapid degradation of these mRNA. His laboratory has been active in identifying proteins that bind to AURE and regulate these events. Of late, he has studied the regulation of CD154 (CD40 ligand), a member of the TNF gene family that plays a critical role in the immune response. In contrast to cytokine genes, CD154 is regulated by its rate of cytoplasmic mRNA turnover and translation. The CD154 3'UTR mRNA contains two separate cis-acting elements, the cytidine-uridine (CU)- and cytidine-adenine (CA)-rich elements that respectively regulate these two activities. Interestingly the CA rich element is polymorphic in the human; certain polymorphisms have been associated with the development of rheumatoid arthritis and systemic lupus erythematosus.

These findings have prompted Dr. Rigby to begin translational studies of patients with rheumatologic disease to determine if: a) CD154 dysregulation is present; b) Is this dysregulation influenced by disease activity; c) Does this dysregulation correlate with CA-repeat polymorphisms? In this manner, Dr. Rigby will begin to address epigenetic and genetic factors that regulate the expression of this critical immunoregulatory molecule.


Selected Publications:

 

Regulation of Pseudomonas aeruginosa-Mediated Neutrophil Extracellular Traps.
Skopelja-Gardner S, Theprungsirikul J, Lewis KA, Hammond JH, Carlson KM, Hazlett HF, Nymon A, Nguyen D, Berwin BL, Hogan DA, Rigby WFC
Front Immunol. 2019;10:1670. doi: 10.3389/fimmu.2019.01670. Epub 2019 Jul 18.
PMID: 31379861

MRI Results Following Discontinuation of Methotrexate in Patients With Rheumatoid Arthritis Treated With Subcutaneous Tocilizumab: The COMP-ACT MRI Substudy.
Peterfy C, Kremer J, Rigby W, Singer N, Birchwood C, Gill D, Reiss W, Pei J, Michalska M
J Rheumatol. 2019 Jun 1; pii: jrheum.180953. doi: 10.3899/jrheum.180953. Epub 2019 Jun 1.
PMID: 31154414

Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study.
Smolen JS, Pangan AL, Emery P, Rigby W, Tanaka Y, Vargas JI, Zhang Y, Damjanov N, Friedman A, Othman AA, Camp HS, Cohen S
Lancet. 2019 Jun 8;393(10188):2303-2311. doi: 10.1016/S0140-6736(19)30419-2. Epub 2019 May 23.
PMID: 31130260

Autoimmunity to bactericidal/permeability-increasing protein in bronchiectasis exhibits a requirement for Pseudomonas aeruginosa IgG response.
Skopelja-Gardner S, Theprungsirikul J, Meagher RE, Beliveau CM, Bradley KE, Avery M, Henkle E, Siegel S, Gifford AH, Winthrop KL, Rigby WFC
Eur Respir J. 2019 Feb;53(2) pii: 1801891. doi: 10.1183/13993003.01891-2018. Epub 2019 Feb 7.
PMID: 30385530

Triple Positivity for Anti-Citrullinated Protein Autoantibodies, Rheumatoid Factor, and Anti-Carbamylated Protein Antibodies Conferring High Specificity for Rheumatoid Arthritis: Implications for Very Early Identification of At-Risk Individuals.
Verheul MK, Bohringer S, van Delft MAM, Jones JD, Rigby WFC, Gan RW, Holers VM, Edison JD, Deane KD, Janssen KMJ, Westra J, Brink M, Rantapaa-Dahlqvist S, Huizinga TWJ, van der Helm-van Mil AHM, van der Woude D, Toes REM, Trouw LA
Arthritis Rheumatol. 2018 Nov;70(11):1721-1731. doi: 10.1002/art.40562. Epub 2018 Sep 16.
PMID: 29781231

Sustained Response Following Discontinuation of Methotrexate in Patients With Rheumatoid Arthritis Treated With Subcutaneous Tocilizumab: Results From a Randomized, Controlled Trial.
Kremer JM, Rigby W, Singer NG, Birchwood C, Gill D, Reiss W, Pei J, Michalska M
Arthritis Rheumatol. 2018 Aug;70(8):1200-1208. doi: 10.1002/art.40493. Epub 2018 Jun 14.
PMID: 29575803

Review of Routine Laboratory Monitoring for Patients with Rheumatoid Arthritis Receiving Biologic or Nonbiologic DMARDs.
Rigby WFC, Lampl K, Low JM, Furst DE
Int J Rheumatol. 2017;2017:9614241. doi: 10.1155/2017/9614241. Epub 2017 Oct 31.
PMID: 29225625

"NETtling" the host: Breaking of tolerance in chronic inflammation and chronic infection.
Skopelja-Gardner S, Jones JD, Rigby WFC
J Autoimmun. 2018 Mar;88:1-10. doi: 10.1016/j.jaut.2017.10.008.
PMID: 29100671

Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors.
Gladman D, Rigby W, Azevedo VF, Behrens F, Blanco R, Kaszuba A, Kudlacz E, Wang C, Menon S, Hendrikx T, Kanik KS
N Engl J Med. 2017 Oct 19;377(16):1525-1536. doi: 10.1056/NEJMoa1615977.
PMID: 29045207

Editorial: Anti-Citrullinated Protein Antibody, Anti-Carbamylated Protein Antibody, and Rheumatoid Arthritis: Azurophilic Granules Sing the Blues.
Rigby WFC, Skopelja-Gardner S, Jones JD
Arthritis Rheumatol. 2017 Dec;69(12):2251-2255. doi: 10.1002/art.40238.
PMID: 28853239

View more publications on PubMed