Department of Pediatrics Annual Report – 2020

Molecular Genetics

Solving the mystery of disease through research

The primary mission of the Division of Molecular Genetics is research. The division operates across many scientific and administrative areas of the university, with studies ranging from the physiology and genetics of body weight homeostasis to neurogenetics of autism and the genetic causes of rare inborn errors of structure, metabolism, and development.

The division’s 70 staff members receive research support totaling ~$10 million per annum from a wide range of sources.

Division director Rudolph Leibel, MD, and his laboratory focus on:

  • The genetics of obesity and non-insulin-dependent diabetes (diabetes mellitus type 2); lab members have mapped, cloned, and identified mutations in the obese, diabetes, and fatty genes in humans, rats, and mice
  • Defining the physiological basis by which signaling networks regulate body mass and composition

The laboratory is also the location of the Molecular Biology/Molecular Genetics Core laboratory of the New York Nutrition/Obesity Research Center and the Columbia Diabetes Research Center (both NIH Centers), and the lab co-administers research activities for the Naomi Berrie Diabetes Center.

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

Russell Berrie Programs

  • Pre-Translational Research Program: Provides funding in order to lower barriers to rapid translation of basic diabetes research findings into human subjects
  • 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
  • Frontiers in Diabetes Research: A full-day symposium with international speakers on a topic related to diabetes and metabolism. Provides research support for seven fellows in labs throughout the Columbia and NYC biomedical institutions

New York Obesity Research Center: 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: Provides research support for investigators pursuing research on diabetes and metabolic disorders.

Genetic Basis Disease Programs

The division has programs focused on determining the genetic basis of a range of diseases, including:

  • Cardiac disease
  • Breast Cancer Family Registry Cohort
  • Pancreatic cancer high-risk assessment
  • Center for Research on the Ethical, Legal and Social Implications of Psychiatric Genetics
  • Genetic studies and diagnosis of developmental disorders
  • Gene mutation and rescue in human diaphragmatic hernia
  • Developmental mechanisms of trachea-esophageal birth defects
  • Ovid Columbia (neurogenetic disorders)
  • Pulmonary arterial hypertension
  • Duchenne Muscular Dystrophy
  • Autism and neurodevelopmental disorders

Genomic Medicine Integration

  • Whole exome and whole genome sequencing
  • Columbia Electronic Medical Records and Genomics (eMERGE): Integration of genomic medicine in the electronic medical record (EMR)
  • Precision Medicine
    • To identify the right treatment for the right patient at the right time
    • To increase the effectiveness of health care at reduced cost with improved outcomes, decreased adverse effects, greater patient satisfaction
    • Precision medicine used to maintain health
    • Use information from the individual patient in real time to stratify disease risk, response, and ultimately find the most effective and acceptable options for the individual to maintain health and quality of life
    • Develop a comprehensive program for an extremely large and ethnically/economically/educationally diverse population that is not available in other locations around the country

Faculty Research Areas of Expertise

Dr. Leibel leads a team of investigators whose research focuses on the molecular physiology and genetics of body weight regulation and diabetes in humans and rodents. Team members include:

  • Michael Rosenbaum, MD: Regulation and responses of behavioral, metabolic, neurological, neuroendocrine, and autonomic system to changes in body weight
  • Vidhu Thaker, MD: Genetic determinants of severe early childhood obesity and its clinical consequences for children from minority populations
  • Yiying Zhang, PhD: Metabolism of obesity and leptin biology. C neuronal development
  • Wendy K. Chung, MD, PhD: Performs human genetic research of monogenic and complex traits, including congenital heart disease, pulmonary hypertension, breast cancer, pancreatic cancer, obesity, diabetes, and autism. She has extensive experience mapping and cloning human genes
  • 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. Use of 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
  • George Stratigopoulos, PhD: Identifying new molecular pathways of the central nervous system involved in body weight regulation
  • Lori Zeltser, PhD: Explores how development and environment impacts body weight regulation and influence later susceptibility to obesity and eating disorders.


  • The division provides opportunities for graduate students to receive training and mentorships leading to a doctoral degree
  • Frontiers in Diabetes Research provides one- or two-year fellowship awards to postdocs and awards to research scholars
  • The Russell Berrie Obesity Research Initiative provides awards to senior investigators for research projects in the neuroscience of ingestive behavior and body weight regulation
  • The Molecular Genetics Fellowship is a non-ACGME accredited program that provides opportunities for postdoctoral training in the genetic basis for monogenic or complex medical and physiological phenotypes using both human and animal models

New Appointments

Associate Research Scientists

  • Todor Arsov, PhD

Postdoctoral Research Scientists

  • Haluk Kavus, MD
  • Tania C. Vasquez
  • Bryan Gonzalez, PhD
  • Daniela Georgieva, PhD
  • Qian Du, MD
  • Zhangji Dong, PhD
  • Yanjun Xu, PhD
  • Hannah Glover, PhD
  • Olaya Fernández Gayol, PhD
  • Grazia Iannello, PhD

Honors and Awards

Vidhu Thaker, MD

  • Jr. Faculty Diversity Award, 2020
  • Louis V. Gerstner, Jr Scholar (VP&S), 2019

Wendy Chung, MD, PhD

  • Medal for Distinguished Contributions in Biomedical Science (New York Academy of Medicine), 2019
  • Rare Impact Award (National Organization of Rare Disorders), 2019
  • Mentor of the Year (College of Dental Medicine – Columbia University)
  • Fundamentals Outstanding Teacher Award, Class of 2021 (Columbia University)

Rudolph Leibel, MD

  • Presidential Medal of the Obesity Society, 2020
  • American Diabetes Association Albert Renold Award, 2019

Michael Rosenbaum, MD

  • TOPS Award (The Obesity Society), 2019

Julia Wynn, MS

  • Department of Pediatrics Innovation Nucleation Award, 2020

Major Grants

  • Molecular genetic analysis of human obesity: Identify the genes that mediate susceptibility to obesity in humans. NIH/NIDDK; R01DK52431-24. -Principal Investigators: Leibel and Chung.
  • New York Obesity Research Center studies the etiology, treatment strategies and the physiology of weight. NIH/NIDDK; P30DK26687-41. Principal Investigators: Leibel and Chung;  Co-investigators: Claudia Doege, Dieter Egli; Vidhu Thaker, Yiying Zhang; Charles LeDuc.
  • Diabetes & Endocrinology Research Center to promote interactions among research groups in diabetes, obesity, lipid metabolism, structural biology, immunology and beta cell transplantation. NIH/NIDDK; P30DK63608-18. Principal Investigators: Accili/Leibel.
  • Functional imaging and eating behavior among FTO genotypes in pre-obese children. NIH/NIDDK; R01DK097399-05. Principal Investigators: Michael Rosenbaum, Laurel Mayer.
  • Study of coding variants in human obesity and their functional characterization using human iPSC-derived cellular models. NIH/NIDDK; 5R01DK110113-05. Principal Investigators: Loos/Doege.
  • Center for identification and study of individuals with atypical diabetes mellitus. NIH/NIDDK; U54DK118612-02. Principal Investigators: Phillipson/Leibel.
  • Evaluating the effects of diabetes linked exome sequence variants on beta cell differentiation, proliferation, function and adaptation to hyperglycemia. Regeneron Pharmaceuticals. Principal Investigators: Leibel, Chung, Egli, Doege.
  • Research initiative on the neurobiology of obesity. Russell Berrie Foundation. Principal Investigators: Leibel/Zuker.
  • Role of the kinesin KIF1A in neurological disease. NIH/NINDA; 1R01NS114636-01. Principal Investigators: Vallee/Chung,
  • Molecular approaches to gene identification in congenital heart disease. NIH/NINDS; U01HL131003. Principal Investigator: Chung.
  • Gene mutation and rescue in human diaphragmatic hernia. NIH/NICHD; 1P01HD068250PI. Principal Investigators: Donahue/Chung.
  • Prenatal cytogenetic diagnosis by genome sequencing to investigate the use of molecular testing by genome sequence analysis in prenatal diagnostic testing. NIH/NICHHD/ELSI; R01HD055651060. Principal Investigators: Wapner/Chung.
  • Integrate cancer genomics data in genetic studies and diagnosis of developmental disorders. NIH/NHLBI; R03HL147197. Principal Investigators: Chung /Shen.
  • Breast Cancer Family Cohort. NIH/NHLBI; U01CA1649204. Principal Investigators: Terry/Chung.
  • Deep phenotyping in electronic health records for genomic medicine to develop data science and informatics methods to accelerate deep phenotyping using the unstructured data in electronic health records for genomic diagnostic decision support and genomic knowledge discovery. NLM/NHGRI; 1R01LM012895-01. Principal Investigators: Weng /Chung.
  • Development of recommendations and policies for genetic variant reclassification. NIH/NHGRI; R01HG010365. Principal Investigators: Chung/Appelbaum.
  • Identifying and applying genetic variation relevant to clinical outcomes for individuals with congenital heart disease. NIH/NHLBI; 1U01HL153009. Principal Investigators: Chung /Shen/Gelb.
  • Genetics of early childhood obesity and its clinical implications. NIH/NIDDK; K23 DK110539. Principal Investigator: Vidhu Thaker.

Selected Publications

Zuccaro MV, Xu J, Mitchell C, Marin D, Zimmerman R, Rana B, Weinstein E, King RT, Palmerola KL, Smith ME, Tsang SH, Goland R, Jasin M, Lobo R, Treff N, Egli D. Allele-specific chromosome removal after Cas9 cleavage in human embryos. 183(6): 1650-1664. E15. doi: 183(6).

Skowronski AA, LeDuc CA, Foo KS, Goffer Y, Burnett LC, Egli D and Leibel RL, Physiological consequences of transient hyperleptinemia during discrete developmental periods on body weight in mice 2020. Science Translational Medicine. 2020; 12(524). PubMed PMID: 31894105

Ganapathi M, Padgett LR, Yamada K, Devinsky O, Willaert R, Person R, Au PB, Tagoe J, McDonald M, Karlowicz D, Wolf B, Lee J, Shen Y, Okur V, Deng L, LeDuc CA, Wang J, Hanner A, Mirmira RG, Park MH, Mastracci TL, Chung WK. Recessive rare variants in deoxyhypusine synthase, an enzyme involved in the synthesis of hypusine, are associated with a neurodevelopmental disorder. Am J Hum Genet. 2019 Feb 7; 104(2): 287-298. doi: 10.1016/ j.ajhg.2018.12.017. Epub 2019 Jan 17. PMID: 30661771.

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, Brüning JC, Egli D, Costa R, Berbari N, Leibel RL, Stratigopoulos G. Ciliary gene RPGRIP1L is required for hypothalamic arcuate neuron development. JCI Insight. 2019 Feb 7; 4(3). pii: 123337. doi: 10.1172/jci.insight.123337. [Epub ahead of print] PMID: 30728336.

Nees SN, Chung WK. The genetics of isolated congenital heart disease. Am J Med Genet C Semin Med Genet. 2019 Dec 26. doi: 10.1002/ajmg.c.31763. PMID:31876989.

Garofalo DC, Sorge ST, Hesdorffer DC, Winawer MR, Phelan JC, Chung WK, Ottman R. Genetic attribution and perceived impact of epilepsy in multiplex epilepsy families. Epilepsia. 2019 Nov; 60(11): 2286-2293. doi: 10.1111/epi.16352. Epub 2019 Oct 6. PMID: 31587270.

Rosenbaum M, Hall KD, Guo J, Ravussin E, Mayer LS, Reitman ML, Smith SR, Walsh BT, Leibel RL. Glucose and lipid homeostasis and inflammation in humans following an isocaloric ketogenic diet. Obesity (Silver Spring). 2019 Jun;27(6):971-981. doi: 10.1002/oby.22468. Epub 2019 May 8. PMID: 31067015.

Rosenbaum M, Goldsmith RL, Haddad F, Radom-Aizik S, Gallagher D, Leibel RL. Triiodothyronine and leptin repletion in humans similarly reverse weight-loss induced changes in skeletal muscle. Am. J. Physiol., 2018; 315: E771-79.

Gonzalez B, Creusot R, Sykes M, Egli D. How safe are universal pluripotent stem cells? Cell Stem Cells. 2020 Mar 5; 26 (3): 307-308. PMID:32142661.


CRISPR, Stem Cells, and Neonatal Diabetes

Newborns seldom get diabetes, but when they do, it’s almost always caused by a mutation in a single gene that prevents pancreas cells from secreting insulin. A combination of CRISPR—a gene editing technique—and stem cell technology could replace these defective cells with fully functional insulin-producing cells, Columbia scientists have shown in a new proof-of-principle study. 


Crispr Gene Editing Can Cause Unwanted Changes in Human Embryos, Study Finds

A powerful gene-editing tool called Crispr-Cas9, which this month nabbed the Nobel Prize in Chemistry for two female scientists, can cause serious side effects in the cells of human embryos, prompting them to discard large chunks of their genetic material, a new study has found.

The New York Times

Rudolph L. Leibel, MD, Named American Diabetes Association’s 2019 Albert Renold Award Recipient

The American Diabetes Association (ADA) will present the 2019 Albert Renold Award to Rudolph L. Leibel, MD. This award recognizes an individual whose career is distinguished by outstanding achievements in the training and mentorship of diabetes research scientists and in the facilitation of diabetes research.

American Diabetes Association