Claudia A. Doege, MD

Profile Headshot

Overview

Academic Appointments

  • Assistant Professor of Pathology and Cell Biology

Languages

  • German

Credentials & Experience

Education & Training

  • MD, 1998 Humboldt University, Faculty of Medicine (Germany)

Honors & Awards

2013 - Keystone Symposium (Stem Cell Regulation, Alberta, Canada) Travel Award

Research

Patient-specific hypothalamic neurons to elucidate human obesity

Obesity arguably accounts for the greatest proportion of illness, incapacity, and societal cost of any single health problem in the U.S. Upwards of 60% of risk variance for obesity is genetically conveyed. And the majority of the known obesity-related genes are expressed in the brain, acting in part through hypothalamic neurons affecting food intake. Access to human neuro-cellular model systems is critical to gaining insights into the molecular neurophysiology of body weight regulation in humans. The Doege lab utilizes patient-specific hypothalamic neurons to elucidate the molecular mechanisms of human monogenic obesity (e.g., melanocortin-4 receptor deficiency). These studies may ultimately lead to the development of novel therapeutic strategies for human obesity.

Our focus is on:

1) The creation of a series of human hypothalamic cell types from patient-specific induced pluripotent stem cells (iPSC).

2) The investigation of the molecular mechanisms underlying monogenic forms of obesity.

3) The identification of modifiers of monogenic obesity that reduce penetrance.

To address these questions, we employ stem cell-based approaches (patient-specific iPSC, in vitro differentiation into specific hypothalamic neuron subtypes), genome-editing tools such as CRISPR, whole-exome/genome sequencing, single-cell whole-transcriptome sequencing, cell biology and biochemical approaches.

Research Interests

  • Molecular mechanisms of human obesity
  • Patient-specific disease modeling
  • Human stem cell-derived hypothalamic neurons
  • Genome editing

Grants

THE MOLECULAR GENETIC ANALYSIS OF HUMAN OBESITY (Federal Gov)

Sep 24 2016 - Aug 31 2021

NEW YORK OBESITY RESEARCH CENTER (Federal Gov)

Dec 1 1996 - Mar 31 2021

GENERATION AND INTEGRATION OF NEW CNS NEURONS BY IN VIVO DIRECTED CONVERSION (Federal Gov)

Sep 30 2012 - Jul 31 2017

REDUCED PROHORMONE PROCESSIN(PROHORMONE CONVERTASE 1 HYPOACTIVITY) AS A MECHANISM FOR PRADER-WILLI SYNDROME. PRE-CLINICAL ANALYSES. (Private)

Jul 15 2016 - Jul 14 2017

STUDY OF CODING VARIANTS IN HUMAN OBESITY AND THEIR FUNCTIONAL CHARACTERIZATION USING HUMAN IPSC-DERIVED CELLULAR MODELS (Federal Gov)

Sep 17 2016 - Jun 30 2017

HUMAN INDUCED NEURONAL STEM CELL MODELS OF FAMILIAL ALZHEIMER S DISEASE (Federal Gov)

Jul 1 2012 - Jun 30 2017

TO FUNCTIONALLY EVALUATE POSSIBLE DISEASE-CAUSING VARIANTS IDENTIFIED IN WES/WGS TO DETERMINE PATHOGENICITY OF RARE VARIANTS AND DISEASE MECHANISM. (Private)

Jul 1 2014 - Jun 30 2016

COLLABORATIVE RESEARCH PROGRAM RELATING TO THE STUDY OF GENETIC DISEASES THROUGH WHOLE EXOME/GENOME SEQUENDING (Private)

Jul 1 2014 - Jun 30 2016

COLLABORATIVE EFFORT IN STEM CELL BIOLOGY (Private)

Jul 1 2010 - Jun 30 2014

GENE EXPRESSION REGULATORY CIRCUITRY AND MICRORNAS IN MIDBRAIN DOPAMINE NEURONS (Federal Gov)

Dec 1 2008 - Nov 30 2013

HUMAN IPS CELL-BASED MODELS FOR NEURODEGENERATION (NY State Gov)

Jan 1 2009 - Jun 30 2012

INTRACELLULAR SIGNALING CASCADES IN IPS REPROGRAMMING (NY State Gov)

Jan 1 2009 - Jun 30 2012

Selected Publications

Wang, L., Sui, L., Panigrahi, S. K., Meece, K., Xin, J., Kim, J., Gromada, J., Doege, C. A., Wardlaw, S. L., Egli, D. & Leibel, R.L. (2017). PC1/3 deficiency impacts pro-opiomelanocortin processing in human embryonic stem cell-derived hypothalamic neurons. Stem Cell Reports, S2213-6711(16)30311-3. PMID: 28132887

Doege, C.A., Inoue, K., Yamashita, T., Rhee, D.B., Travis, S., Fujita, R., Guarnieri, P., Bhagat, G., Vanti, W.B., Shih, A., Levine, R.L., Nik, S., Chen, E.I., & Abeliovich, A. (2012). Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2. Nature, 488(7413), 652-655. PMID: 22902501

Doege, C. A. & Abeliovich, A. (2014). Dementia in a dish. Biological Psychiatry, 75(7), 558-564. PMID: 24629668

Abeliovich, A. & Doege, C. A. (2009). Reprogramming therapeutics: iPS cell prospects for neurodegenerative disease. Neuron, 61(3), 337-339. PMCID: PMC3659427 

Andang, M., Moliner, A., Doege, C.A., Ibanez, C.F., & Ernfors, P. (2008). Optimized mouse ES cell culture system by suspension growth in a fully defined medium. Nature Protocols, 3, 1013-1017. PMID: 18536648 

Burri, L., Varlamov, O., Doege, C.A., Hofmann, K., Beilharz, T., Rothman, J.E., Söllner, T.H., & Lithgow, T. (2003). A SNARE required for retrograde transport to the endoplasmic reticulum. Proceedings of the National Academy of Sciences of the United States of America, 100(17), 9873-9877. PMCID: PMC187870 

Varlamov, O., Volchuk, A., Rahimian, V., Doege, C.A., Paumet, F., Eng, W.S., Arango, N., Parlati, F., Ravazzola, M., Orci, L., Söllner, T.H., & Rothman, J.E. (2004). i-SNAREs: inhibitory SNAREs that fine-tune the specificity of membrane fusion. The Journal of Cell Biology, 164(1), 79-88. PMCID: PMC2171956 

Doege, C.A., Kerskens, C.M., Romero, B.I., Brunecker, P., Junge-Hulsing, J., von Pannwitz, W., Muller, B., & Villringer, A. (2003) Assessment of diffusion and perfusion deficits in patients with small subcortical ischemia. American Journal of Neuroradiology, 24(7), 1355-1363. PMID: 12917127

Doege, C.A., Tavakolian, R., Kerskens, C.M., Romero, B.I., Lehmann, R., Einhaupl, K.M., & Villringer, A. (2001) Perfusion and diffusion magnetic resonance imaging in human cerebral venous thrombosis. Journal of Neurology, 248(7), 564-571. PMID: 11517997

Doege, C.A., Kerskens, C.M., Romero, B.I., Brunecker, P., Junge-Hulsing, J., Muller, B., & Villringer, A. (2000) MRI of small human stroke shows reversible diffusion changes in subcortical gray matter. Neuroreport 11(9), 2021-2024. PMID: 10884064