Dr. Keppler-Noreuil's clinical and research interests include natural history and clinical characterization, genetic studies, and therapeutic interventions of somatic overgrowth disorders, including Proteus syndrome and PIK3CA-Related Overgrowth Spectrum (PROS), as well as other malformations and genetic disorders, including OEIS complex/cloacal exstrophy and Bardet-Biedl syndrome. Her studies of Proteus syndrome and PROS have included: descriptive analyses of craniofacial abnormalities, cardiac, risk for thromboembolism, prevalence and complications of vascular malformations and tumors.
Her work has included further delineation of the clinical findings and complications in PROS and Proteus syndrome, and the role of somatic mutations in the PI3K/AKT/mTOR pathway in these disorders and in tumorigenesis. As principal investigator and co-lead of the PIK3CA-Related Overgrowth Multinational Investigation of Sirolimus Efficacy (PROMISE), she has initiated the pilot treatment trial in collaboration with the University of Cambridge, United Kingdom, and the University of Dijon, France, as part of the Consortium for Overgrowth Disorder Management and Evaluation of Therapeutics (COMET). Future therapeutic trials of alternative agents for PROS are being planned. She is also lead associate investigator of a Phase 1 dose finding trial of an AKT inhibitor, ARQ 092, in children and adults with Proteus syndrome.
Dr. Keppler-Noreuil's other areas of research have included clinical delineation of multiple malformation syndromes, and studies of epidemiology and pathogenesis of birth defects, inherited and chromosomal disorders. She has been involved in helping characterize the genetic etiology and clinical presentation of several multiple congenital anomaly syndromes seen in the Rare Diseases Group within the Clinical Genomics Section of her branch.
She also continues to collaborate in research involving the Centers for Birth Defects Research and Prevention (CBDRP), including studies of OEIS complex/ cloacal exstrophy, Dandy-Walker malformation and hydrocephalus. She has been co-author on studies of the role of in vitro fertilization in birth defects, development of a registry and guidelines for assessment of potential congenital anomalies in women on clinical trials, as well as those treated for cancer during pregnancy, twinning and major birth defects, and risk factors for Dandy-Walker malformation.
Dr. Keppler-Noreuil is lead investigator of the descriptive epidemiological study of cloacal exstrophy and related malformations, "Clinical and risk factor analysis of cloacal defects in the National Birth Defects Prevention Study (NBDPS)," and a sequencing study of cloacal exstrophy and bladder exstrophy with CBDPS and NISC. She is interested in further exploring the role of somatic genetic mutations in the etiology of cloacal exstrophy. She will collaborate on a multistage investigation of clinical characteristic, environmental exposures and genetic variants for congenital hydrocephalus.
Posted: January 24, 2017