Carolyn Sue Richards, PhD
3181 SW Sam Jackson Park Road
Mail Code: MP350
Portland, OR 97239
Office: 503 494-4416
Fax: 503 494-6922
The focus of my clinical research laboratory is development of sequence-based testing for rare disorders, development of custom analysis to address copy number variants, design of algorithms using analysis tools for interpretation of sequence variations, and translation of these products into clinical practice.
Prior to joining OHSU I have a long-standing history of research collaborations translating into sequence-based clinical testing for numerous rare genetic disorders, including Lynch syndrome, familial adenomatous polyposis, Rothmund Thompson syndrome, Li-Fraumeni syndrome, X-linked ocular albinism, and Duchenne/Becker muscular dystrophy. My laboratory here has developed strong collaborations with OHSU researchers, including the Hayflick laboratory, resulting in the translation of testing for Pantothenate Kinase Associated Neuropathy and Infantile Neuroaxonal Dystrophy into the Molecular Diagnostic Center at OHSU. In addition, collaborations with the Grompe laboratory and the Olson laboratory have resulted in the introduction of clinical molecular testing for multiple Fanconi Anemia genes and generated a research project focused on understanding the mechanism of mosaicism through molecular studies.
For rare disorders that require sequence analysis, additional technologies are required to assess copy number variants. We are working toward developing custom microarray analysis to compliment our sequence analysis. In addition, we plan to develop custom targeted oligonucleotide microarrays for resequencing analysis of rare disorders, syndromes associated with multiple genes, and inherited cancer genes. We have established a collaboration with the OHSU microarray core for this project.
A major challenge in sequence-based diagnostics is defining the biological and functional significance of novel sequence variants. We are addressing this challenge through a project that evaluates multiple predictive analysis software tools to assess variants of unknown clinical significance, with the goal of defining a master algorithm that will have clinical utility. We are currently collaborating with OHSU Bioinformatics group on developing this project.
Additional interests of our laboratory include development and assessment of pharmacogenetic testing. In particular, we are collaborating with Kaiser investigators on an OCTRI-funded project to genotype breast cancer patients treated with tamoxifen.
Wu G, Wu W, Hegde M, Fawkner M, Chong B, Love DR, Su L-K, Lynch P, Snow K, Richards CS. Detection of sequence variations in the Adenomatous Polyposis Coli (APC) gene using denaturing high-performance liquid chromatography. GeneticTesting 5(4):281-290, 2002.
Hegde M, Lewis RA, Richards CS. Diagnostic testing for X-linked ocular albinism (X-OA1) with a hierarchical mutation screening protocol. Genetic Testing 6(1):7-14, 2002.
Hegde M, Blazo M, Odenbaugh D, Richards C. Assay validation for identification of HNPCC-causing mutations in mismatch repair genes MLH1, MSH2, and MSH6. J Mol Diag. 2005 Oct;7(4):525-34.
Hegde M, Blazo M, Chong B, Chin LHE, Ward PA, Chintagumpala MM, Kim JY, Ayala G, Plon SE, Richards CS. A homozygous mutation in MSH6 causes Turcot Syndrome. Clin Cancer Res. 2005 Jul 1;11(13):4689-93.
Richards CS and Hegde MR. Familial Adenomatous Polyposis. In:Encyclopedia of Genomics, Proteomics and Bioinformatics. M. Dunn, L. Jorde, P. Little, S. Subramaniam, eds., B. Korf (section editor), John Wiley & Sons, UK (2005)
Johnson M, Yoshitomi M, Richards CS. A Comparative Study of Five Technologically Diverse CFTR Testing Platforms. Journal of Molecular Diagnostics 2007, Vol. 9, No. 3, 401-407.
Grody WW, Richards CS. New quality assurance standards for rare disease testing. Genet Med. 2008 May;10(5):320-4.
Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE; Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee.ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med. 2008 Apr;10(4):294-300.
Nabil N. Moghrabi, Monique A. Johnson, Xiaoman Zhu, Muhsen Al-Dhalimy, Susan Olson, Markus Grompe, C. Sue Richards. Validation of Fanconi Anemia Group A Subtyping Using an Integrated Strategy for Rapid and Comprehensive FANCA Molecular Analysis and Identification of Novel FANCA Mutations. Genetics in Medicine 11(3) March 2009.
Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (CS Richards, panel member) Recommendations from the EGAPP Working Group: can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? Genet Med. 2009 Jan;11(1):15-20.
Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. (CS Richards, panel member) Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives.Genet Med. 2009 Jan;11(1):35-41.
Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. (CS Richards, panel member) Recommendations from the EGAPP Working Group: can tumor gene expression profiling improve outcomes in patients with breast cancer?Genet Med. 2009 Jan;11(1):66-73.