Rebecca Ahrens-Nicklas, MD, PhD

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Assistant Professor of Pediatrics (Human Genetics)
Department: Pediatrics
Graduate Group Affiliations

Contact information
Children's Hospital of Philadelphia
5014 Colket Translational Research Building
3501 Civic Center Blvd
Philadelphia, PA 19104
Office: 215-834-7679
BS (Pharmacology)
Duke University, 2003.
PhD (Physiology & Biophysics)
Weill Cornell Medical College, 2010.
MD (MD/PhD Program)
Weill Cornell/ Rockefeller/Sloan-Kettering, 2011.
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Description of Research Expertise

Research Interests: We study rare genetic disorders of the heart and brain both to further our understanding of basic biology and to develop new therapies for our patients.

Keywords: biochemical genetics, inborn errors of metabolism, electrophysiology, neuroscience, cardiomyopathy, targeted therapies, genetics, genomics, clinical genetics, gene discovery

Research Details: Our lab aims to develop better treatments for inherited disorders of biochemistry (i.e., inborn errors of metabolism, IEMs) by studying how these diseases alter the electrical activity of the brain and heart. While individually rare, IEMs occur in approximately 1/1,500 births. The vast majority of patients have neurologic and/or cardiac symptoms that do not respond to therapy, even if a treatment can improve serum biochemical markers of disease.

Using genetic, biochemical, and electrophysiologic techniques in cells, model organisms, and human subjects, we investigate the mechanisms that drive neurologic and cardiac dysfunction in patients with IEMs. We also evaluate the efficacy of a number of new therapeutic strategies for IEM (including small-molecule, network-directed, and gene therapies).

We hypothesize that genetic defects in biochemical pathways alter the development and evolution of electrical circuits in excitable tissues. To improve outcomes in patients with IEMs, therapies will have to correct both the biochemical defect and the secondary circuit-level pathology that directly drives patients’ symptoms.

Selected Publications

Ahrens-Nicklas RC, Tecedor L, Hall AH, Lysenko E, Cohen AS, Davidso, BL, Marsh E: Neuronal network dysfunction precedes storage and neurodegeneration in a lysosomal storage disorder. JCI insight 4(21): e131961, Nov 2019 Notes: doi: 10.1172/jci.insight.131961.

Ahrens-Nicklas RC, Pappas CT, Farman GP, Mayfield RM, Larrinaga TM, Medne L., Ritter A. Krantz ID, Murali C, Lin KY, Berger JH, Yum SW, Carreon CK, Gregorio CC: Disruption of cardiac thin filament assembly arising from a mutation in LMOD2: A novel mechanism of neonatal dilated cardiomyopathy. Sci Adv 5(9): eaax2066, Sep 2019 Notes: doi: 10.1126/sciadv.aax2066. eCollection 2019 Sep.

Ritter A, Cuddapah S, Degenhardt K, Kaspersky S, Johnson MP, O'Connor MJ, Ahrens-Nicklas RC: Fetal cardiomyopathy in neurofibromatosis type I: Novel phenotype and review of the literature. Am J Med Genet A 179(6): 1042-1046, Jun 2019 Notes: doi: 10.1002/ajmg.a.61123. Epub 2019 Mar 28.

Schlotawa L, Adang L, DeCastro M, Ahrens-Nicklas R.C : Multiple Sulfatase Deficiency. GeneReviews. Adam MP, Arranger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A (eds.). University of Washington, Mar 2019.

Ahrens-Nicklas RC, Ganetzky RD, Rush PW, Conway RL, Ficicioglu C: Characteristics and outcomes of patients with formiminoglutamic aciduria detected through newborn screening. J Inherit Metab Dis 42(1): 140-146, Jan 2019 Notes: doi: 10.1002/jimd.12035.

Yun S, Reynolds RP, Petrof I, White A, Rivera PD, Segev A, Gibson AD, Suarez M, DeSalle MJ, Ito N, Mukherjee S, Richardson DR. Kang CE, Ahrens-Nicklas R C, Soler I, Chetkovich DM, Kourrich S, Coulter DA, Eisch AJ: Stimulation of entorhinal cortex-dentate gyrus circuitry is antidepressive. Nat Med 24(5): 658-666, May 2018 Notes: doi: 10.1038/s41591-018-0002-1. Epub 2018 Apr 16.

Ahrens-Nicklas RC, Schlotawa L, Ballabio A, Brunetti-Pierri N, De Castro M, Dierks T, Eichler F, Ficicioglu C, Finglas A, Gaertner J, Kirmse B, Klepper J, Lee M, Olsen A, Parenti G, Vossough A, Vanderver A, Adang LA: Complex care of individuals with multiple sulfatase deficiency: Clinical cases and consensus statement. Mol Genet Metab 123(3): 337-346, Mar 2018 Notes: doi: 10.1016/j.ymgme.2018.01.005. Epub 2018 Jan 31.

Ahrens-Nicklas, RC, Umanah GK, Sondheimer N, Deardorff MA, Wilkens AB, Conlin LK, Santani AB, Nesbitt A, Juulsola J, Ma E, Dawson TM, Dawson, VL, Marsh ED: Precision therapy for a new disorder of AMPA receptor recycling due to mutations in ATAD1. Neurol Genet 3(1): e130, Feb 2017 Notes: doi: 10.1212/NXG.0000000000000130. eCollection 2017 Feb.

Ahrens-Nicklas RC, Whitaker AM, Kaplan P, Cuddapah S, Burfield J, Blair J, Brochi L, Yudkoff M, Ficicioglu C: Efficacy of early treatment in patients with cobalamin C disease identified by newborn screening: a 16-year experience. Genet Med 19(8): 926-935, Aug 2017 Notes: doi: 10.1038/gim.2016.214. Epub 2017 Feb 2.

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Last updated: 06/26/2024
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