My research seeks to understand the biological relationships between the circadian clock and diseases of the developing brain.

MEDICAL SERVICES

Departments

Programs

Languages

  • English

EDUCATION

Undergraduate Degree

  • Brown University , Providence , RI

Medical School

  • Albert Einstein College of Medicine , Bronx , NY

Internship

Pediatrics
  • Children's Hospital of Montefiore , 2004 , Bronx , NY

Residency

Neurology
  • Boston Children's Hospital , 2005 , Boston , MA

Fellowship

Sleep Medicine
  • Boston Children's Hospital / Beth Israel Deaconess Medical Center , 2008 , Boston , MA

PROFESSIONAL HISTORY

As a child neurologist and sleep physician, I am especially aware of the importance of sleep in children with neurological disease. My research seeks to understand the biological relationships between the circadian clock and diseases of the developing brain.

We have identified the core circadian clock protein BMAL1 as a regulator of protein synthesis. BMAL1 promotes circadian rhythms in protein synthesis as a substrate of the mechanistic target of rapamycin (mTOR) pathway, a critical gauge of nutritive status and stress in all cells, including the brain.

We have characterized a novel, potentially modifiable, link between the biological timing system and cellular signaling. Corroborating these findings, we have found strong phenotypes in mouse models of the mTOR-opathy Tuberous Sclerosis Complex. Using a combination of mouse behavior, cell biology, biochemistry, and proteomic approaches, my research investigates how circadian timing mechanisms are disrupted in disease.

My teaching activities include supervision of medical students, neurology residents, sleep medicine fellows, graduate students, and post-doctoral fellows. My educational role straddles both clinical and basic scientific domains and have widely at local, national, and international venues. 

CERTIFICATIONS

  • American Board of Psychiatry and Neurology, Child and Adolescent Neurology
  • American Board of Psychiatry and Neurology, Sleep Medicine

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. Persistent CO2 reactivity deficits are associated with neurological dysfunction up to one year after repetitive mild closed head injury in adolescent mice. J Cereb Blood Flow Metab. 2021 Jul 06; 271678X211021771. View abstract
  2. Adaptor protein complex 4 deficiency: a paradigm of childhood-onset hereditary spastic paraplegia caused by defective protein trafficking. Hum Mol Genet. 2020 01 15; 29(2):320-334. View abstract
  3. Mechanisms of sleep and circadian ontogeny through the lens of neurodevelopmental disorders. Neurobiol Learn Mem. 2019 04; 160:160-172. View abstract
  4. Proteomics, Post-translational Modifications, and Integrative Analyses Reveal Molecular Heterogeneity within Medulloblastoma Subgroups. Cancer Cell. 2018 09 10; 34(3):396-410.e8. View abstract
  5. mGluR5 Modulation of Behavioral and Epileptic Phenotypes in a Mouse Model of Tuberous Sclerosis Complex. Neuropsychopharmacology. 2018 05; 43(6):1457-1465. View abstract
  6. Aberrant Proteostasis of BMAL1 Underlies Circadian Abnormalities in a Paradigmatic mTOR-opathy. Cell Rep. 2017 07 25; 20(4):868-880. View abstract
  7. Neural Circuitry of Wakefulness and Sleep. Neuron. 2017 Feb 22; 93(4):747-765. View abstract
  8. Impaired Mitochondrial Dynamics And Mitophagy In Neuronal Models Of Tuberous Sclerosis Complex. Cell Rep. 2016 11 15; 17(8):2162. View abstract
  9. Impaired Mitochondrial Dynamics and Mitophagy in Neuronal Models of Tuberous Sclerosis Complex. Cell Rep. 2016 10 18; 17(4):1053-1070. View abstract
  10. Direct current stimulation induces mGluR5-dependent neocortical plasticity. Ann Neurol. 2016 08; 80(2):233-46. View abstract
  11. The Circadian Protein BMAL1 Regulates Translation in Response to S6K1-Mediated Phosphorylation. Cell. 2015 May 21; 161(5):1138-1151. View abstract
  12. The neurology of mTOR. Neuron. 2014 Oct 22; 84(2):275-91. View abstract
  13. Copy number variation plays an important role in clinical epilepsy. Ann Neurol. 2014 Jun; 75(6):943-58. View abstract
  14. Fragile X syndrome therapeutics: translation, meet translational medicine. Neuron. 2013 Jan 23; 77(2):212-3. View abstract
  15. 16p11.2-related paroxysmal kinesigenic dyskinesia and dopa-responsive parkinsonism in a child. Neurology. 2009 Aug 11; 73(6):479-80. View abstract
  16. Melatonin deficiency and disrupted circadian rhythms in pediatric survivors of craniopharyngioma. Neurology. 2009 Jul 28; 73(4):323-5. View abstract
  17. Insomnia of childhood. Curr Opin Pediatr. 2008 Dec; 20(6):641-9. View abstract
  18. CNS relapse of acute myelogenous leukemia masquerading as pseudotumor cerebri. Pediatr Neurol. 2008 Nov; 39(5):355-7. View abstract
  19. Kawasaki disease: cerebrovascular and neurologic complication. Uncommon Causes of Stroke. 2008. View abstract
  20. Kawasaki disease: cerebrovascular and neurologic complications. Uncommon Causes of Stroke (editor LR Caplan). 2008. View abstract
  21. Disruption of Circadian Melatonin Secretion in Pediatric Craniopharyngioma Survivors with Hypersomnolence. Sleep (Abstract). 2008. View abstract
  22. Mating worms and the cystic kidney: C. elegans as a model for renal disease. Pediatric Nephrology. 2005; 20:1531-36. View abstract
  23. Mate searching in Caenorhabditis elegans: a genetic model for sex drive in a simple in vertebrate. Journal of Neuroscience. 2004; 24:7427-34. View abstract
  24. The genetic basis of male mating behavior. Journal of Neurobiology. 2003; 54:93-110. View abstract
  25. Genetics of Sexually Motivated Behavior in Caenorhabditis elegans. 2003. View abstract