Solving the Mystery of Disease Through Research

Dna test infographic showing barcoding of genome map.

Department of Pediatrics Annual Report – 2024

Molecular Genetics

2024 Pediatrics Annual Report banner

The primary mission of the Division of Molecular Genetics is research. The division operates across several scientific and administrative areas of the university, with studies focusing on the physiology and genetics of body weight homeostasis and diabetes and the molecular physiology of DNA replication.

The laboratory is also the location of the Molecular Biology/Molecular Genetics Core laboratory of the New York Nutrition and Obesity Research Center and the Columbia Diabetes Research Center (both NIH centers).

The division has nationally recognized clinical and research programs, including: 

  • Russell Berrie Foundation Programs 
    • Berrie Program in Cellular Therapies of Diabetes: Evaluates the molecular basis for the development and function of insulin-producing cells in the pancreas and hypothalamic cells of the brain 
    • Russell Berrie Foundation Obesity Research Initiative: Promotes transformative research in the neuroscience of ingestive behavior and body weight regulation 
  • New York Nutrition and Obesity Research Center (NYNORC) 
    • NYNORC focuses on the etiology, pathophysiology, and complications of obesity,  treatment strategies, the physiology of weight regulation, and new tools and strategies for the study of nutrition and obesity. 
  • Columbia Diabetes Research Center 
    • The center provides research support for investigators pursuing research on diabetes and metabolic disorders. 
  • Screening for Monogenic Forms of Diabetes and Obesity
    • We receive samples from around the world, including samples for genetic evaluation of neonatal diabetes, isolated familial diabetes, MODY, Wolfram syndrome, and obesity. 

Faculty Research Areas of Expertise 

  • Michael Rosenbaum, MD: Regulation and responses of behavioral, metabolic, neurological, neuroendocrine, and autonomic systems to changes in body weight. 
  • Vidhu Thaker, MD: Genetic determinants of severe early childhood obesity and its clinical consequences for  children from minority populations; Impact maternal metabolism on fetal development related to obesity. 
  • Yiying Zhang, PhD: Metabolism of obesity and leptin biology; Molecular physiology of the Prader Willi Syndrome. 
  • Claudia Doege, MD: Elucidates the neuro-molecular mechanisms of human obesity to gain insights into the molecular neurophysiology of body weight regulation in humans. 
  • Dietrich M. Egli, PhD: Studies genome stability and the cell cycle in early embryonic development during somatic cell reprogramming and cell differentiation. Uses stem cell-derived human islets to understand molecular physiology of diabetes. 
  • Charles LeDuc, PhD: Focuses on the molecular neurophysiology of the regulation of mammalian energy homeostasis. 
  • Lori Zeltser, PhD: Explores how development and environment impacts body weight regulation and influence later susceptibility to obesity and eating disorders. 
  •  Rudolph Leibel, MD: The genetics of obesity and non-insulin-dependent diabetes (diabetes mellitus type 2); Uses cells derived from human stem cells to understand the biology of body weight regulation and diabetes. Role of the cerebellum in body weight homeostasis. 

Education 

The Division of Molecular Genetics provides opportunities for graduate students to receive training and mentorships leading to a doctorate degree. Interested students who have been accepted into the Columbia University Graduate School of Arts and Sciences can rotate through our laboratories before deciding whether to consider their research projects in our labs under the mentorship of our faculty. 

Promotions

New Appointments

  • Ekaterina Semenova, PhD
  • Xueting Li, PhD

Honors and Awards

  • Vidhu Thaker, MD
    • Presentation at Obesity Journal Symposium at The Obesity Society Meeting, November 3-6, 2024, San Antonio, TX. One of the five papers selected for presentation for a special issue from an international competition: The association of higher offspring early-childhood weight gain with prepregnancy metabolic and bariatric surgery. 
    • Selected to participate in the Academic Pediatric Society and Society for Pediatric Research (APS and SPR) Journeys and Frontiers in Pediatric Research, a program designed to encourage and support promising pediatric investigators
    • Selected for SPR Mid-Career Research Leadership Development Program, a career development program to aid mid-career pediatrician-scientists and other scientists and researchers focused on child health
  • Ashby Thompson, PhD
    • Abbott Lingo Investigator Initiated Study support -- Continuous Glucose Monitoring (CGM) for the Identification of Novel Mediators of Glucose Homeostasis  

Major Grants

  • New York Nutrition-Obesity Research Center studies the etiology, treatment strategies and the physiology of weight. NIH/NIDDK. P30DK26687-44. (4/15/21-3/31/26). Principal Investigator: Dympna Gallagher, Tony Ferrante, Rudolph Leibel, MD; Co-Investigators: Claudia Doege, MD, Dieter Egli, PhD, Yiying Zhang, PhD, and Charles LeDuc, PhD. 
  • Diabetes & Endocrinology Research Center to promote interactions among research groups in diabetes, obesity, lipid metabolism, structural biology, immunology and beta cell transplantation. NIH/NIDDK. P30DK63608-23.(03/22/2023-12/31/2027) Principal Investigators: Domenico Accili, MD and Rudolph Leibel, MD. 
  • The GUARDIAN (Genomic Uniform screening Against Rare Diseases In All Newborns) is a pilot research study using genome sequencing and analysis of 250 conditions to screen newborns for treatable genetic conditions using the dried blood spot collected already for screening. Principal Investigators: Wendy Chung and Rudy Leibel 
  • Neuroanatomic and functional characterization of cerebellar circuits mediating ingestive behaviors. NIH/NIDDK. R01DK131086-03. (06/01/22-05/31/26). Principal Investigators: Nathaniel Sawtell, PhD and Rudolph Leibel, MD. 
  • Center for identification and study of individuals with atypical diabetes mellitus. NIH/NIDDK. U54DK118612-06. (09/18/2018-5/31/29) Principal Investigators: Louis Philipson, MD, PhD and Rudolph Leibel, MD. 
  • Predictors of recidivism to obesity in weight-reduced individuals. NIH/NIDDK. 4UH3 DK128302-03. (4/1/21-3/31/26). Principal Investigators: Rudolph Leibel, MD, Dympna Gallagher, EdD, Laurel Mayer, MD, and Michael Rosenbaum, MD. 
  • The Foundation for Prader-Willi Research. 11/01/2023 – 04/30/2025. SNORD109a expression across the human hypothalamus and cerebellum PI: Claudia Doege, MD.  
  • Virtual systemic identification of drug targets of obesity candidate genes. NIH/NIDDK. R01DK135938-01. 4/1/23 - 3/31/28.  PI: Lu, Yingchang / CU: Claudia Doege, MD 
  • Establishing the role of OCRL as a novel ciliary gene in weight regulation in human and murine models. NIDDK 1R21DK129893-01A1. (9/1/22-5/31/25). Principal Investigator: Vidhu Thaker, MD; Co-Investigator: George Stratigopoulos, PhD. 
  • Defining the pathways of cardiometabolic health after weight loss. (04/01/2024 – 12/31/2028)  R01 DK136134. Principal Investigator: Vidhu Thaker 
  • Genetic investigations of cardiometabolic disease: pleiotropy, gene x environment and causal inference analyses. (10/2024 – 07/2029) R01 DK136796.  Co-Investigator: Vidhu Thaker 
  • Dissemination and Outreach Core, Prospective Genetic Risk Evaluation and Assessment 
  • (PROGRESS) in Autism. NIH/NICHD. 1P50HD109879-01. (9/1/22-8/31/27). Principal Investigators: Jeremy Veenstra-VanderWeele, MD and Wendy Chung, MD, PhD 
  • Developmental Mechanisms of Trachea-Esophageal Birth Defects. NIH/NICHD. P01HD093363-06. (6/1/23-5/31/28). Principal Investigators: Aaron Zorn, PhD, and Wendy Chung, MD, PhD. Co-Investigator: Yufeng Shen. PhD. 
  • Causes and Consequences of DNA Replication Stress in the Mammalian Preimplantation Embryo. NIH R01HD113698-01. (7/23/24-3/31/28). Principal Investigator: Dieter Egli, PhD.
  • Causes and Consequences of DNA Replication Stress in Human Embryonic Development. Keck Foundation WMKF24-2097. (7/1/2024-6/30/2027). Principal Investigator: Dieter Egli, PhD.
  • Thymic selection abnormalities in Type 1 Diabetes. NIH. R01AI177872-01. 7/1/23-5/31/28. Principal Investigators: Sykes, Megan (Contact PI); Winchester, Robert J. (MPI) Co-Investigator: Dieter Egli, PhD. 
  • Dartmouth College P&F award. P30DK117469 (07/01/2023-06/30/2025). CFTR function in human beta cells in a stem cell model of CFRD. Principal Investigator: Dean Madden, /CU:  Dieter Egli, PhD. 
  • DNA repair pathway choice mediates somatic cell reprogramming. NIH/NIGMS. R01GM132604. (7/1/2023-6/30/2025). Principal Investigator: Dieter Egli, PhD.
  • US-Israel Binational Science Foundation. 10/1/22-9/30/26. The essentialome of the early differentiation and disease modeling using genome-wide screening in haploid human pluripotent stem cells. Principal Investigator: Nissim Benvenisty, MD, PhD; Co-Principal Investigator: Dietrich Egli, PhD. 
  • TRx/ACT Pilot Award. 8/1/23-7/31/25. Preventing genome instability and developmental failure in human fertility treatments. Principal Investigator: Dieter Egli, PhD. 
  • The CSCI and the Seed Fund Award. 12/1/23-11/30/24.  DNA replication dynamics and genome fragility in pancreatic beta cells. Principal Investigator: Dieter Egli, PhD. 
  • BIOSYNC: Bioelectronics for the Delivery of Synthetic Therapeutics with Wireless Control ARPA-H NIH: ARPA-H-MIA-24-01-02. (09/17/2024 - 09/16/2030).  Principal Investigator: 
  • Kenneth Shepard, PhD Columbia Engineering PI. R. Leibel, Co-Investigator.  The objective of this proposal is to develop an implantable device for the treatment of obesity through the temporal- and dose-controlled release of peptide satiety signals manufactured by implanted cells. The device is wirelessly controlled from a smart phone. 
  • Clinical and Translational Science Award (CTSA). NIH 2UL1TR001873-07 (6/30/22 - 05/31/27).  Principal Investigator: Muredach Reilly; Co-Investigator Associate Program Director: Michael Rosenbaum, MD 
  • Metabolic impact of antiretroviral therapy regimens on people living with HIV. NIH/NIDDK:   R01 DK131503-01 (9/01/22-8/30/25) Principal Investigator: Rupak Shivakoti; Co-Investigator: Michael Rosenbaum, MD  
  • Mechanisms addressing the causal relationships of sleep, circadian rhythms, and cardiometabolic health. NIH  R35 HL155670 (06/01/22-05/31/2028) Principal Investigator: Marie P St-Onge; Co-Investigator: Michael Rosenbaum, MD  

Selected Publications

  • Thaker
    • Sena C, Della Torre J, Garg E, Zheng H, Partida I, Thaker SK, Woo-Baidal J, Shamsian DV, Rausch J, Thaker VV*. Association of psychological attributes with eating behaviors in children 5-12 years of age during COVID-19 pandemic as a model for stress. Obesity, In press. 
    • Thaker VV, Crimmins N, Yates KP, Mencin A, Xanthakos S. Reply: Prevalence of subclinical hypothyroidism and longitudinal thyroid stimulating hormone changes in youth with metabolic dysfunction-associated steatotic liver disease: an observational study. Hepatology. 2024 Nov 12. doi: 10.1097/HEP.0000000000001157. Epub ahead of print. PMID: 39531209. 
    • Untalan M, Crimmins N, Yates KP, Mencin A, Xanthakos S, Thaker VV*. Prevalence of subclinical hypothyroidism and longitudinal thyroid stimulating hormone changes in youth with metabolic dysfunction-associated steatotic liver disease: an observational study. Hepatology. 2024 Sep 18. doi: 10.1097/HEP.0000000000001095. Epub ahead of print. PMID: 39292865. 
    • Hilaire MJ, Babcock A, White G, Masson CF, Salem RM, Reddy UM, Gallagher D, LeDuc CA, Thaker VV*. The association of higher offspring early-childhood weight gain with prepregnancy metabolic and bariatric surgery. Obesity (Silver Spring). 2024 Nov;32(11):2012-2023. doi: 10.1002/oby.24166. PMID: 39497631. 
    • Rajamoorthi A, Zheng H, Skowronski AA, Zork N, Reddy U, Tung PW, Kupsco A, Gallagher D, Salem RM, Leibel RL, LeDuc CA, Thaker VV*. Association of gestational and childhood circulating C-peptide concentrations in the hyperglycemia and adverse pregnancy outcomes follow-up study. Diabetes Res Clin Pract, In press 
    • Nigam S, Zhu M, Shoemaker A, Gross AC, Fox C, Thaker VV*. Novel model of childhood appetitive traits in children with obesity. In review. 
    • Lardieri A, Thaker VV, Citron-Zafrin K, Corsi E, Garvin J, Zacharoulis S, Ladas EJ. Pharmacologic management of obesity in neuro-oncology. Case Rep Oncol, In press. 
    • Ebrahim N, Khadegi N, Deng S, Qian K, Yao Z, Thaker SK, May B, Patibandala N, Lopez-Pintado S, Thaker VV*. Classification of obesity using longitudinal clinical BMI data and its association with cardiometabolic risk and socio-economic measures. In review. 
    • Thaker VV*, Kwee LC, Chen H, Bahnson J, Ilkayeva O, Muehlbauer MJ, Wolfe B, Purnell JQ, Pi-Sunyer X, Newgard CB, Shah SH, Laferrère B; Look AHEAD Research Group. Metabolite signature of diabetes remission in individuals with obesity undergoing weight loss interventions. Obesity (Silver Spring). 2024 Feb;32(2):304-314. doi: 10.1002/oby.23943. PMID: 37962326. 
  • Doege
    • Al-Dalahmah O, Lam M, McInvale JJ, Qu W, Nguyen T, Mun JY, Kwon S, Ifediora N, Mahajan A, Humala N, Winters T, Angeles E, Jakubiak KA, Kühn R, Kim YA, De Rosa MC, Doege CA, Paryani F, Flowers X, Dovas A, Mela A, Lu H, DeTure MA, Vonsattel JP, Wszolek ZK, Dickson DW, Kuhlmann T, Zaehres H, Schöler HR, Sproul AA, Siegelin MD, De Jager PL, Goldman JE, Menon V, Canoll P, Hargus G. Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons. Cell Stem Cell. 2024 May 2;31(5):676-693.e10. doi: 10.1016/j.stem.2024.03.013. Epub 2024 Apr 15. PMID: 38626772; PMCID: PMC11373574. 
  • Ashby Thompson
    • Ashby-Thompson M, Heshka, S, Anderson A, Pownall H, Laferrère B, Balasubramanyam A, Heymsfield SB, Wadden T, Gallagher D. Long-term sustained effects of the Look AHEAD lifestyle intervention on body composition among adults with type 2 diabetes. Obesity (Silver Spring). 2024 Jun;32(6):1093-1101. doi: 10.1002/oby.24025. Epub 2024 May 13. PMID: 38741246. 
  • Egli
    • Xu, S., Ning, W., Michael, V.Z., Jeannine, G., Timour, B., Amnon, K., and Dieter, E. (2023). DNA replication in early mammalian embryos is patterned, predisposing lamina-associated regions to fragility. Nat Commun. 2024 Jun 19;15(1):5247. PMID: 38898078. PMCID: PMC11187207 
    • Georgieva, D., Wang, N., Taglialatela, A., Jerabek, S., Reczek, C., Lim, P.X., Sung, J., Du, Q., Horiguchi, M., Jasin, M., Ciccia, A., Baer, R., Egli, D*., 2024. BRCA1 and 53BP1 Regulate Reprogramming Efficiency by Mediating DNA Repair Pathway Choice at Replication-associated Double-Strand Breaks. Cell Reports, 2024 Mar 29;43(4):114006. PMID:38554279; PMC11272184 
    • Zhang, Y., Sui, L., Du, Q., Haataja, L., Yin, Y., Viola, R., Xu, S., Nielsson, C.U., Leibel, R.L., Barbetti, F., Arvan, P., Egli, D.* 2024. Permanent neonatal diabetes-causing insulin mutations have dominant negative effects on beta cell identity. Mol Metab 80, 101879. 10.1016/j.molmet.2024.101879. PMID:37745320 ; PMC10839447 
  • Leibel
    • Zhu, N., LeDuc, C.A., Fennoy, I., Laferrère, B., Doege, C.A., Shen, Y., Chung, W.K. and Leibel, R.L., 2023. Rare predicted loss of function alleles in Bassoon (BSN) are associated with obesity. NPJ.    Genomic Medicine, 8(1), p.33. 
    • Zhang Yuwei, Sui Lina, Du Qian, Haataja Leena, Yin Yishu, Viola Ryan, Xu Shuangyi, Nielsson Christian Ulrik, Leibel Rudolph L, Barbetti Fabrizio, Arvan Peter, Egli Dieter. Permanent neonatal diabetes-causing insulin mutations have dominant negative effects on beta cell identity. Mol Metab 80:101879, 2024 Feb. Epub 2024 Jan 16. 
  • Rosenbaum 
    • Lee, I., H. Mitsumoto, S. Lee, E. Kaskaris, M. Rosenbaum, P. Factor-Litwak, J.W. Nieves. Low glycemic index diet is associated with faster disease progression in amyotrophic lateral sclerosis. Ann. Neurol., 95:217-29, 2024. 
    • Lee, I., H. Mitsumoto, S. Lee, E. Kaskaris, M. Rosenbaum, P. Factor-Litwak, J.W. Nieves. Reply to Glycemic Index/Load Effect on ALS Progression - Potential Interaction with Riluzole. Ann Neurol, 96:208-09 2024. 
    • A.S. Hamdi, R. Molinski, B. Bohn, S. Roy, M. Rosenbaum, B. Paster, M. Yuzefpolskaya, P.C. Colombo, P.N. Papaganou, M. Desvarieux, D.R. Jacobs, R.T. Demmer. Clinical Attachment Loss is Cross-Sectionally Associated with Elevated Glucose among Adults without Diabetes. J. Clin. Periodont., 5:522-35, 2024. 
    • Singh, S., L.S. Mayer, M. Rosenbaum, M.R. Lowe. Weight history correlates of resting energy expenditure in women with bulimia nervosa. Int. J Eating Disord, 57:1899-1910 2024.