Claudia A. Doege, MD

  • Associate Professor of Pathology and Cell Biology at CUMC
Profile Headshot

Overview

Academic Appointments

  • Associate Professor of Pathology and Cell Biology at CUMC

Languages

  • English
  • German

Credentials & Experience

Education & Training

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

Committees, Societies, Councils

International Society of Stem Cell Research

Society for Neuroscience

Honors & Awards

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

Research

Obesity is a major health concern in the U.S. contributing significantly to type 2 diabetes, heart disease, liver fat deposition, several types of cancer and severe COVID-19. We aim to identify therapeutically tractable hypothalamic pathways not previously implicated in body weight regulation and thus, to develop novel therapeutic strategies for obesity.

Our strategies include: 1) functional studies of novel obesity variants/genes in human stem cell-derived hypothalamic neurons; 2) single-cell transcriptomics and epigenomics to characterize the diversity of cell types in the human hypothalamus and how these populations of cells are altered in obesity; 3) computational biology approaches to integrate GWAS and functional genomics data from the human brain and patient-specific hypothalamic cells to characterize disease-perturbed gene networks and molecular disease mechanisms.

Research Interests

Molecular mechanisms of human obesity, patient-specific induced pluripotent stem cell-derived hypothalamic neurons, genome editing, single-cell transcriptomics and epigenomics of the human hypothalamus, functional genomics of human metabolic diseas

Selected Publications

  • Herb BR, Glover HJ, Bhaduri A, Colantuoni C, Bale TL, Siletti K, Hodge R, Lein E, Kriegstein AR, Doege CA, Ament SA. Single-cell genomics reveals region-specific developmental trajectories underlying neuronal diversity in the human hypothalamusSci Adv. 2023;9(45):eadf6251. Co-corresponding author
  • Zhu N, LeDuc CA, Fennoy I, Laferrère B, Doege CA, Shen Y, Chung WK, Leibel RL. Rare predicted loss of function alleles in Bassoon (BSN) are associated with obesity. NPJ Genom Med. 2023;8(1):33.
  • De Rosa MC, Glover HJ, Stratigopoulos G, LeDuc CA, Su Q, Shen Y, Sleeman MW, Chung WK, Leibel RL, Altarejos J, Doege CA. Gene expression atlas of energy balance brain regions. JCI Insight. 2021;6(16):e149137.
  • Wang L, Liu Y, Stratigopoulos G, Panigrahi S, Sui L, Zhang Y, Leduc CA, Glover HJ, De Rosa MC, Burnett LC, Williams DJ, Shang L, Goland R, Tsang SH, Wardlaw S, Egli D, Zheng D, Doege CA, Leibel RLBardet-Biedl syndrome proteins regulate intracellular signaling and neuronal function in patient-specific iPSC-derived neurons. J Clin Invest. 2021;131(8):e146287. Co-corresponding author
  • Pahl MC, Doege CA, Hodge KM, Littleton SH, Leonard ME, Lu S, Rausch R, Pippin JA, De Rosa MC, Basak A, Bradfield JP, Hammond RK, Boehm K, Berkowitz RI, Lasconi C, Su C, Chesi A, Johnson ME, Wells AD, Voight BF, Leibel RL, Cousminer DL, Grant SFA. Cis-regulatory architecture of human ESC-derived hypothalamic neuron differentiation aids in variant-to-gene mapping of relevant complex traits. Nat Commun. 2021;12(1):6749. Co-first author
  • Hammond RK, Pahl MC, Su C, Cousminer DL, Leonard ME, Lu S,Doege CA, Wagley Y, Hodge KM, Lasconi C, Johnson ME, Pippin JA, Hankenson KD, Leibel RL, Chesi A, Wells AD, Grant SFA. Biological constraints on GWAS SNPs at suggestive significance thresholds reveal additional BMI loci. Elife. 2021;10:e62206.
  • Lasconi C, Pahl MC, Cousminer DL, Doege CA, Chesi A, Hodge KM, Leonard ME, Lu S, Johnson ME, Su C, Hammond RK, Pippin JA, Terry NA, Ghanem LR, Leibel RL, Wells AD, Grant SFA. Variant-to-Gene-Mapping Analyses Reveal a Role for the Hypothalamus in Genetic Susceptibility to Inflammatory Bowel Disease. Cell Mol Gastroenterol Hepatol. 2021;11(3):667-682.
  • Yaghootkar H, Zhang Y, Spracklen CN, Karaderi T, Huang LO, Bradfield J, Schurmann C, Fine RS, Preuss MH, Kutalik Z, Wittemans LBL, Lu Y, Metz S, Willems SM, Li-Gao R, Grarup N, Wang S, Molnos S, Sandoval-Zárate AA, Nalls MA, Lange LA, Haesser J, Guo X, Lyytikäinen LP, Feitosa MF, Sitlani CM, Venturini C, Mahajan A, Kacprowski T, Wang CA, Chasman DI, Amin N, Broer L, Robertson N, Young KL, Allison M, Auer PL, Blüher M, Borja JB, Bork-Jensen J, Carrasquilla GD, Christofidou P, Demirkan A, Doege CA, Garcia ME, Graff M, Guo K, Hakonarson H, Hong J, Ida Chen YD, Jackson R, Jakupovi? H, Jousilahti P, Justice AE, Kähönen M, Kizer JR, Kriebel J, LeDuc CA, Li J, Lind L, Luan J, Mackey DA, Mangino M, Männistö S, Martin Carli JF, Medina-Gomez C, Mook-Kanamori DO, Morris AP, de Mutsert R, Nauck M, Prokic I, Pennell CE, Pradhan AD, Psaty BM, Raitakari OT, Scott RA, Skaaby T, Strauch K, Taylor KD, Teumer A, Uitterlinden AG, Wu Y, Yao J, Walker M, North KE, Kovacs P, Ikram MA, van Duijn CM, Ridker PM, Lye S, Homuth G, Ingelsson E, Spector TD, McKnight B, Province MA, Lehtimäki T, Adair LS, Rotter JI, Reiner AP, Wilson JG, Harris TB, Ripatti S, Grallert H, Meigs JB, Salomaa V, Hansen T, Willems van Dijk K, Wareham NJ, Grant SFA, Langenberg C, Frayling TM, Lindgren CM, Mohlke KL, Leibel RL, Loos RJF, Kilpeläinen TO. Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity. Diabetes. 2020 Dec;69(12):2806-2818. >
  • De Rosa MC, Chesi A, McCormack S, Zhou J, Weaver B, McDonald M, Christensen S, Liimatta K, Rosenbaum M, Hakonarson H, Doege CA, Grant SFA, Hirschhorn JN, Thaker VV. Characterization of rare variants in MC4R in African American and/or Latino children with severe early onset obesity. J Clin Endocrinol Metab. 2019;104(7):2961-2970. 
  • Quarta C, Fisette A, Xu Y, Colldén G, Legutko B, Tseng YT, Reim A, Wierer M, De Rosa MC, Klaus V, Rausch R, Thaker VV, Graf E, Strom TM, Poher AL, Gruber T, Le Thuc O, Cebrian-Serrano A, Kabra D, Bellocchi L, Woods SC, Pflugfelder GO, Nogueiras R, Zeltser L, Grunwald Kadow IC, Moon A, García-Cáceres C, Mann M, Treier M, Doege CA, Tschöp MH. Functional identity of hypothalamic melanocortin neurons depends on Tbx3. Nat Metab. 2019;1(2):222-235.
  • Wang L, De Solis AJ, Goffer Y, Birkenbach KE, Engle SE, Tanis R, Levenson JM, Li X, Rausch R, Purohit M, Lee JY, Tan J, De Rosa MC, Doege CA, Aaron HL, Martins GJ, Bruning JC, Egli D, Costa R, Berbari N, Leibel RL, Stratigopoulos G. Ciliary gene RPGRIP1L is required for hypothalamic arcuate neuron development. JCI Insight. 2019;4(3):e123337.
  • Stratigopoulos G, De Rosa MC, LeDuc CA, Leibel RL, Doege CA. DMSO increases efficiency of genome editing at two non-coding loci. PloS One. 2018;13(6):e0198637.PubM
  • Wang L, Sui L, Panigrahi SK, Meece K, Xin Y, Kim J, Gromada J, Doege CA, Wardlaw SL, Egli D, Leibel RL. PC1/3 Deficiency Impacts Pro-opiomelanocortin Processing in Human Embryonic Stem Cell-Derived Hypothalamic Neurons. Stem Cell Reports. 2017;8(2):264-277.
  • Doege CA, Inoue K, Yamashita T, Rhee DB, Travis S, Fujita R, Guarnieri P, Bhagat G, Vanti WB, Shih A, Levine RL, Nik S, Chen EI, Abeliovich A. Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2. Nature. 2012;488(7413):652-655.PubMedComment in News & Views
  • Andang M, Moliner A, Doege CA, Ibanez CF, Ernfors P. Optimized mouse ES cell culture system by suspension growth in a fully defined medium. Nat Protoc. 2008;3(6):1013-1017.